JP5443975B2 - Novel sulfonamide derivative or salt thereof - Google Patents
Novel sulfonamide derivative or salt thereof Download PDFInfo
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- JP5443975B2 JP5443975B2 JP2009512960A JP2009512960A JP5443975B2 JP 5443975 B2 JP5443975 B2 JP 5443975B2 JP 2009512960 A JP2009512960 A JP 2009512960A JP 2009512960 A JP2009512960 A JP 2009512960A JP 5443975 B2 JP5443975 B2 JP 5443975B2
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- 0 ****NC(C(N(*)S(*)(=O)=O)=C(**)C(*)=C(*)I)=I Chemical compound ****NC(C(N(*)S(*)(=O)=O)=C(**)C(*)=C(*)I)=I 0.000 description 27
- KOGSGUNJEFEDKS-UHFFFAOYSA-N CC(C)(C)OC(Nc(c([N+]([O-])=O)c1)cc(OCc2ccccc2)c1I)=O Chemical compound CC(C)(C)OC(Nc(c([N+]([O-])=O)c1)cc(OCc2ccccc2)c1I)=O KOGSGUNJEFEDKS-UHFFFAOYSA-N 0.000 description 1
- BPEZWXJHPZVAGI-UHFFFAOYSA-N CC(C)c1cccc(-c(cc(c(NC(OC(C)(C)C)=O)c2)[N+]([O-])=O)c2OCc2ccccc2)c1 Chemical compound CC(C)c1cccc(-c(cc(c(NC(OC(C)(C)C)=O)c2)[N+]([O-])=O)c2OCc2ccccc2)c1 BPEZWXJHPZVAGI-UHFFFAOYSA-N 0.000 description 1
- LSQQHFJCMATGLV-UHFFFAOYSA-N CC(Oc(cccc1)c1C(Nc(cc(cc1)-c2ccccc2)c1N(C)S(C)(=O)=O)=O)=O Chemical compound CC(Oc(cccc1)c1C(Nc(cc(cc1)-c2ccccc2)c1N(C)S(C)(=O)=O)=O)=O LSQQHFJCMATGLV-UHFFFAOYSA-N 0.000 description 1
- FCUAIVXROVBAHB-UHFFFAOYSA-N CN(c(c(N)c1)cc(F)c1-c1ccccc1)S(C)(=O)=O Chemical compound CN(c(c(N)c1)cc(F)c1-c1ccccc1)S(C)(=O)=O FCUAIVXROVBAHB-UHFFFAOYSA-N 0.000 description 1
- FFYUEOXFDLUMIM-UHFFFAOYSA-N CN(c(c(N)c1)ccc1-c(cccc1)c1F)S(C)(=O)=O Chemical compound CN(c(c(N)c1)ccc1-c(cccc1)c1F)S(C)(=O)=O FFYUEOXFDLUMIM-UHFFFAOYSA-N 0.000 description 1
- YIZHJZTVZZOZMO-UHFFFAOYSA-N CN(c(c(N)c1)ccc1-c1ccccc1)S(C)(=O)=O Chemical compound CN(c(c(N)c1)ccc1-c1ccccc1)S(C)(=O)=O YIZHJZTVZZOZMO-UHFFFAOYSA-N 0.000 description 1
- PIMPUVHMMKLDOW-UHFFFAOYSA-N CN(c(c([N+]([O-])=O)c1)cc(F)c1-c1ccccc1)S(C)(=O)=O Chemical compound CN(c(c([N+]([O-])=O)c1)cc(F)c1-c1ccccc1)S(C)(=O)=O PIMPUVHMMKLDOW-UHFFFAOYSA-N 0.000 description 1
- LDUSJQJBLHMYJE-UHFFFAOYSA-N CN(c(ccc(-c1cc(cc[nH]2)c2nc1)c1)c1NC(c1ccccc1OC)=O)S(C)(=O)=O Chemical compound CN(c(ccc(-c1cc(cc[nH]2)c2nc1)c1)c1NC(c1ccccc1OC)=O)S(C)(=O)=O LDUSJQJBLHMYJE-UHFFFAOYSA-N 0.000 description 1
- BCVDCUHDGNUTAB-UHFFFAOYSA-N CN(c(ccc(-c1ccccc1)c1)c1NC(c(cccc1)c1N)=O)S(C)(=O)=O Chemical compound CN(c(ccc(-c1ccccc1)c1)c1NC(c(cccc1)c1N)=O)S(C)(=O)=O BCVDCUHDGNUTAB-UHFFFAOYSA-N 0.000 description 1
- KOHKQBRXHIFXBE-UHFFFAOYSA-N CN(c(ccc(-c1ccccc1)c1)c1NC(c(cccc1)c1O)=O)S(C)(=O)=O Chemical compound CN(c(ccc(-c1ccccc1)c1)c1NC(c(cccc1)c1O)=O)S(C)(=O)=O KOHKQBRXHIFXBE-UHFFFAOYSA-N 0.000 description 1
- FYNVHZYOMCBAKE-UHFFFAOYSA-N CNc(c([N+]([O-])=O)c1)cc(F)c1-c1ccccc1 Chemical compound CNc(c([N+]([O-])=O)c1)cc(F)c1-c1ccccc1 FYNVHZYOMCBAKE-UHFFFAOYSA-N 0.000 description 1
- IFTUKVAJYOQKRS-UHFFFAOYSA-N CNc(c([N+]([O-])=O)c1)ccc1Br Chemical compound CNc(c([N+]([O-])=O)c1)ccc1Br IFTUKVAJYOQKRS-UHFFFAOYSA-N 0.000 description 1
- RWHOBKKTWBUHFX-UHFFFAOYSA-N CS(N(CCC1)c(c([N+]([O-])=O)c2)c1cc2-c1ccccc1)(=O)=O Chemical compound CS(N(CCC1)c(c([N+]([O-])=O)c2)c1cc2-c1ccccc1)(=O)=O RWHOBKKTWBUHFX-UHFFFAOYSA-N 0.000 description 1
- QIYGLEAGBHYNEI-UHFFFAOYSA-N CS(N(CCCc1cc(-c2ccccc2)c2)c1c2NC(c1ccccc1)=O)(=O)=O Chemical compound CS(N(CCCc1cc(-c2ccccc2)c2)c1c2NC(c1ccccc1)=O)(=O)=O QIYGLEAGBHYNEI-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/09—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton the carbon skeleton being further substituted by at least two halogen atoms
-
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/12—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
- C07C311/13—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings the carbon skeleton containing six-membered aromatic rings
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/14—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of rings other than six-membered aromatic rings
-
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/53—Nitrogen atoms
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- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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- C07D241/28—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
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Description
本発明は、プロスタグランジンＥ２（ＰＧＥ２）産生阻害作用を有する新規なスルホンアミド誘導体またはその塩ならびにそれらを含有する抗炎症剤およびＰＧＥ２産生阻害剤に関する。The present invention relates to a novel sulfonamide derivative having a prostaglandin E 2 (PGE 2 ) production inhibitory action or a salt thereof, and an anti-inflammatory agent and a PGE 2 production inhibitor containing them.
非ステロイド系抗炎症剤（ＮＳＡＩＤｓ）は、解熱・鎮痛などを目的として広く処方されている。多くのＮＳＡＩＤｓは、酸性ＮＳＡＩＤｓである。通常、酸性ＮＳＡＩＤｓは、非酸性ＮＳＡＩＤｓより強い抗炎症作用を有し、その主な作用機序は、シクロオキシゲナーゼ（ＣＯＸ）阻害によるプロスタグランジン類の産生抑制である。ＣＯＸには、構成的に発現しているＣＯＸ−１と炎症等で誘導されるＣＯＸ−２の２つのサブタイプが存在することが知られている。
ＮＳＡＩＤｓの抗炎症作用は、炎症部位のＣＯＸ−２阻害に基づくこと、および、消化管障害等のＮＳＡＩＤｓの副作用は、ＣＯＸ−１阻害に基づくことが考えられ（非特許文献１）、そのため、ＣＯＸ−２を選択的に阻害する薬の開発が進められてきた。しかしながら、近年になって、ＣＯＸ−２選択的阻害薬に関するいくつかの臨床試験で心血管リスクの増加傾向が示唆され（非特許文献２）、問題となっている。
ＮＳＡＩＤｓによる消化管障害の発症機序の一つとして、ＮＳＡＩＤｓの直接粘膜傷害作用が考えられている。一般的に酸性ＮＳＡＩＤｓは、胃内のような酸性条件下で非イオン状態となり、胃上皮細胞に容易に取り込まれる。一方、細胞内のような中性条件下ではイオン化するため、ＮＳＡＩＤｓが細胞内に蓄積されて粘膜傷害を直接誘発する可能性が指摘されている（非特許文献３）。したがって、非酸性ＮＳＡＩＤｓは、粘膜障害性が弱く、消化管潰瘍を誘発しにくいと予想される。しかしながら、強い抗炎症作用を有する非酸性ＮＳＡＩＤｓは、これまでに知られていない。
It is considered that the anti-inflammatory action of NSAIDs is based on COX-2 inhibition at the site of inflammation, and the side effects of NSAIDs such as gastrointestinal disorders are based on COX-1 inhibition (Non-Patent Document 1). Development of drugs that selectively inhibit -2 has been promoted. However, in recent years, an increasing tendency of cardiovascular risk has been suggested in several clinical studies on COX-2 selective inhibitors (Non-Patent Document 2), which has become a problem.
As one of the onset mechanisms of digestive tract disorders caused by NSAIDs, direct mucosal damage action of NSAIDs is considered. In general, acidic NSAIDs become nonionic under acidic conditions such as in the stomach and are easily taken up by gastric epithelial cells. On the other hand, it has been pointed out that NSAIDs accumulate in the cells and directly induce mucosal injury because they are ionized under neutral conditions such as intracellular (Non-patent Document 3). Therefore, non-acidic NSAIDs are expected to be less mucosal and less likely to induce gastrointestinal ulcers. However, non-acidic NSAIDs having a strong anti-inflammatory action have not been known so far.
強い抗炎症作用を有する非酸性ＮＳＡＩＤｓが望まれている。 Non-acidic NSAIDs having a strong anti-inflammatory effect are desired.
このような状況下において、本発明者らは鋭意検討を行った結果、一般式［１］
本発明の化合物およびその塩は、強いＰＧＥ２産生阻害作用を有することから、炎症性疾患の治療あるいは予防などの処置ならびにＰＧＥ２の関与する疾患または状態の治療あるいは予防などの処置に有用である。Since the compounds of the present invention and salts thereof have a strong PGE 2 production inhibitory action, they are useful for treatments such as treatment or prevention of inflammatory diseases and treatments such as treatment or prevention of diseases or conditions involving PGE 2. .
以下、本発明化合物について詳述する。
本明細書において、特にことわらない限り、ハロゲン原子とは、フッ素原子、塩素原子、臭素原子およびヨウ素原子を；アルキル基とは、たとえば、メチル、エチル、プロピル、イソプロピル、ブチル、ｓｅｃ−ブチル、イソブチル、ｔｅｒｔ−ブチル、ペンチル、イソペンチル、ヘキシル、ヘプチルおよびオクチルなどの直鎖状または分枝鎖状のＣ１−１２アルキル基を；低級アルキル基とは、たとえば、メチル、エチル、プロピル、イソプロピル、ブチル、ｓｅｃ−ブチル、イソブチル、ｔｅｒｔ−ブチル、ペンチルおよびイソペンチルなどの直鎖状または分枝鎖状のＣ１−６アルキル基を；アルケニル基とは、たとえば、ビニル、アリル、プロペニル、イソプロペニル、ブテニル、イソブテニル、ペンテニル、ヘキセニル、ヘプテニルおよびオクテニルなどの直鎖状または分枝鎖状のＣ２−１２アルケニル基を；アルキニル基とは、たとえば、エチニル、２−プロピニルおよび２−ブチニルなどの直鎖状または分枝鎖状のＣ２−１２アルキニル基を；シクロアルキル基とは、たとえば、シクロプロピル、シクロブチル、シクロペンチルおよびシクロヘキシルなどのＣ３−８シクロアルキル基を；シクロアルケニル基とは、たとえば、シクロプロペニル、シクロブテニル、シクロペンテニルおよびシクロヘキセニルなどのＣ３−８シクロアルケニル基を；アルキレン基とは、たとえば、メチレン、エチレン、プロピレン、ブチレンおよびヘキシレンなどの直鎖状または分枝鎖状のＣ１−６アルキレン基を；Ｃ２−４アルキレン基とは、たとえば、エチレン、プロピレンおよびブチレンなどのＣ２−４アルキレン基を；アルケニレン基とは、たとえば、ビニレン、プロペニレン、１−ブテニレンおよび２−ブテニレンなどの直鎖状または分枝鎖状のＣ２−６アルケニレン基を；Ｃ２−４アルケニレン基とは、たとえば、ビニレン、プロペニレン、１−ブテニレンおよび２−ブテニレンなどのＣ２−４アルケニレン基を；アルキニレン基とは、たとえば、エチニレン、プロピニレン、１−ブチニレンおよび２−ブチニレンなどの直鎖状または分枝鎖状のＣ２−６アルキニレン基を；シクロアルキレン基とは、たとえば、１，１−シクロプロピレン、１，２−シクロプロピレン、１，１−シクロブチレン、１，２−シクロブチレン、１，３−シクロブチレン、１，２−シクロペンチレン、１，３−シクロペンチレン、１，１−シクロヘキシレン、１，２−シクロヘキシレンおよび１，４−シクロヘキシレンなどのＣ３−８シクロアルキレン基を；アリール基とは、たとえば、フェニルおよびナフチルなどの基を；アルアルキル基とは、たとえば、ベンジル、ジフェニルメチル、トリチル、フェネチルおよびナフチルメチルなどのアルＣ１−６アルキル基を；アルコキシ基とは、たとえば、メトキシ、エトキシ、プロポキシ、イソプロポキシ、ブトキシ、イソブトキシ、ｓｅｃ−ブトキシ、ｔｅｒｔ−ブトキシ、ペンチルオキシ、イソペンチルオキシ、ヘキシルオキシ、ヘプチルオキシおよびオクチルオキシなどの直鎖状または分枝鎖状のＣ１−１２アルキルオキシ基を；低級アルコキシ基とは、たとえば、メトキシ、エトキシ、プロポキシ、イソプロポキシ、ブトキシ、イソブトキシ、ｓｅｃ−ブトキシ、ｔｅｒｔ−ブトキシ、ペンチルオキシおよびイソペンチルオキシなどの直鎖状または分枝鎖状のＣ１−６アルキルオキシ基を；アリールオキシ基とは、たとえば、フェノキシおよびナフトキシなどの基を；アルコキシアルキル基とは、たとえば、メトキシメチルおよび１−エトキシエチルなどのＣ１−６アルキルオキシＣ１−６アルキル基を；ヒドロキシアルキル基とは、たとえば、ヒドロキシメチル、ヒドロキシエチル、ヒドロキシプロピル、ヒドロキシブチルおよびヒドロキシペンチルなどのヒドロキシＣ１−６アルキル基を；アルアルキルオキシアルキル基とは、たとえば、ベンジルオキシメチルおよびフェネチルオキシメチルなどのアルＣ１−６アルキルオキシＣ１−６アルキル基を意味する。Hereinafter, the compound of the present invention will be described in detail.
In the present specification, unless otherwise specified, a halogen atom is a fluorine atom, a chlorine atom, a bromine atom and an iodine atom; an alkyl group is, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, Linear or branched C 1-12 alkyl groups such as isobutyl, tert-butyl, pentyl, isopentyl, hexyl, heptyl and octyl; lower alkyl groups include, for example, methyl, ethyl, propyl, isopropyl, Linear or branched C 1-6 alkyl groups such as butyl, sec-butyl, isobutyl, tert-butyl, pentyl and isopentyl; an alkenyl group is, for example, vinyl, allyl, propenyl, isopropenyl, Butenyl, isobutenyl, pentenyl, hexenyl, hepteni And a linear or branched C 2-12 alkenyl group such as octenyl; Alkynyl groups, for example, ethynyl, 2-propynyl and 2-linear butynyl or branched-chain C 2 A -12 alkynyl group; a cycloalkyl group is a C 3-8 cycloalkyl group such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; a cycloalkenyl group is, for example, cyclopropenyl, cyclobutenyl, cyclopentenyl, and cyclo the C 3-8 cycloalkenyl group such as cyclohexenyl; alkylene groups such as methylene, ethylene, propylene, a linear or branched C 1-6 alkylene group such as butylene and hexylene; C 2- 4 alkylene group includes, for example, ethylene, propylene and A C 2-4 alkylene group such as butylene; an alkenylene group is, for example, a linear or branched C 2-6 alkenylene group such as vinylene, propenylene, 1-butenylene and 2-butenylene; the 2-4 alkenylene group, for example, vinylene, propenylene, 1-butenylene and 2-butenylene a C 2-4 alkenylene group such as; the alkynylene group, e.g., ethynylene, propynylene, 1-butynylene and 2-butynylene, etc. A linear or branched C 2-6 alkynylene group; a cycloalkylene group is, for example, 1,1-cyclopropylene, 1,2-cyclopropylene, 1,1-cyclobutylene, 1,2 -Cyclobutylene, 1,3-cyclobutylene, 1,2-cyclopentylene, 1,3-cyclopentylene The aryl group, for example, based on such as phenyl and naphthyl; 1,1-cyclohexylene, C 3-8 cycloalkylene alkylene group such as 1,2-cyclohexylene and 1,4-cyclohexylene and aralkyl Is, for example, an ar C 1-6 alkyl group such as benzyl, diphenylmethyl, trityl, phenethyl and naphthylmethyl; an alkoxy group is, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, linear or branched C 1-12 alkyloxy groups such as tert-butoxy, pentyloxy, isopentyloxy, hexyloxy, heptyloxy and octyloxy; lower alkoxy groups include, for example, methoxy, ethoxy , Propoxy, isopropoxy Linear or branched C 1-6 alkyloxy groups such as cis, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy and isopentyloxy; aryloxy groups include, for example, phenoxy and A group such as naphthoxy; an alkoxyalkyl group, for example, a C 1-6 alkyloxy C 1-6 alkyl group such as methoxymethyl and 1-ethoxyethyl; a hydroxyalkyl group, for example, hydroxymethyl, hydroxyethyl Hydroxy C 1-6 alkyl groups such as hydroxypropyl, hydroxybutyl and hydroxypentyl; aralkyloxyalkyl groups are, for example, ar C 1-6 alkyloxy C 1-6 such as benzyloxymethyl and phenethyloxymethyl. Archi It refers to the group.
アシル基とは、たとえば、ホルミル基、アセチル、プロピオニルおよびイソバレリルなどの直鎖状または分枝鎖状のＣ２−１２アルカノイル基、ベンジルカルボニルなどのアルＣ１−６アルキルカルボニル基、ベンゾイルおよびナフトイルなどの環式炭化水素カルボニル基、ニコチノイル、テノイル、ピロリジノカルボニルおよびフロイルなどの複素環式カルボニル基、スクシニル基、グルタリル基、マレオイル基、フタロイル基ならびにアミノ酸（アミノ酸としては、たとえば、グリシン、アラニン、バリン、ロイシン、イソロイシン、セリン、トレオニン、システイン、メチオニン、アスパラギン酸、グルタミン酸、アスパラギン、グルタミン、アルギニン、リジン、ヒスチジン、ヒドロキシリジン、フェニルアラニン、チロシン、トリプトファン、プロリンおよびヒドロキシプロリンなどが挙げられる。）から誘導されるＮ末端が保護されていてもよい直鎖状または分枝鎖状のα−アミノアルカノイル基を；アルキルオキシカルボニル基とは、たとえば、メトキシカルボニル、エトキシカルボニル、１，１−ジメチルプロポキシカルボニル、イソプロポキシカルボニル、２−エチルヘキシルオキシカルボニル、ｔｅｒｔ−ブトキシカルボニルおよびｔｅｒｔ−ペンチルオキシカルボニルなどの直鎖状または分枝鎖状のＣ１−１２アルキルオキシカルボニル基を；アルアルキルオキシカルボニル基とは、たとえば、ベンジルオキシカルボニルおよびフェネチルオキシカルボニル基などのアルＣ１−６アルキルオキシカルボニル基を；アリールオキシカルボニル基とは、たとえば、フェニルオキシカルボニルなどの基を意味する。Examples of the acyl group include linear or branched C 2-12 alkanoyl groups such as formyl group, acetyl, propionyl and isovaleryl, al C 1-6 alkylcarbonyl groups such as benzylcarbonyl, benzoyl and naphthoyl. Cyclic hydrocarbon carbonyl groups, nicotinoyl, thenoyl, heterocyclic carbonyl groups such as pyrrolidinocarbonyl and furoyl, succinyl group, glutaryl group, maleoyl group, phthaloyl group and amino acids (amino acids include, for example, glycine, alanine, valine) , Leucine, isoleucine, serine, threonine, cysteine, methionine, aspartic acid, glutamic acid, asparagine, glutamine, arginine, lysine, histidine, hydroxylysine, phenylalanine, tyrosine, A linear or branched α-aminoalkanoyl group that may be protected at the N-terminus, derived from ptophan, proline, hydroxyproline, etc .; an alkyloxycarbonyl group is, for example, Linear or branched C 1-12 alkyl such as methoxycarbonyl, ethoxycarbonyl, 1,1-dimethylpropoxycarbonyl, isopropoxycarbonyl, 2-ethylhexyloxycarbonyl, tert-butoxycarbonyl and tert-pentyloxycarbonyl the oxycarbonyl group; the aralkyl oxycarbonyl group, for example, Al C 1-6 alkyloxycarbonyl group such as benzyloxycarbonyl and phenethyloxycarbonyl group; and aryloxycarbonyl group, if Means a group such as phenyloxycarbonyl.
アシルオキシ基とは、たとえば、アセトキシおよびプロピオニルオキシなどの直鎖状または分枝鎖状のＣ２−６アルカノイルオキシ基ならびにベンゾイルオキシなどのアロイルオキシ基を；アシルアルキル基とは、たとえば、アセチルメチル、ベンゾイルメチル、ｐ−ニトロベンゾイルメチル、ｐ−ブロモベンゾイルメチル、ｐ−メトキシベンゾイルメチルおよび１−ベンゾイルエチルなどの基を；アシルオキシアルキル基とは、たとえば、アセトキシメチル、プロピオニルオキシメチルおよびピバロイルオキシメチルなどの基を；アルキルチオ基とは、たとえば、メチルチオ、エチルチオおよびプロピルチオなどのＣ１−６アルキルチオ基を；アルキルチオアルキル基とは、たとえば、メチルチオメチル、エチルチオメチルおよびプロピルチオメチルなどのＣ１−６アルキルチオＣ１−６アルキル基を；アリールチオ基とは、たとえば、フェニルチオなどの基を；アルキルスルホニル基とは、たとえば、メチルスルホニル、エチルスルホニルおよびプロピルスルホニルなどのＣ１−６アルキルスルホニル基を；アリールスルホニル基とは、たとえば、ベンゼンスルホニル、トルエンスルホニルおよびナフタレンスルホニルなどの基を；アルキルスルホニルオキシ基とは、たとえば、メチルスルホニルオキシおよびエチルスルホニルオキシなどのＣ１−６アルキルスルホニルオキシ基を；アリールスルホニルオキシ基とは、たとえば、ベンゼンスルホニルオキシおよびトルエンスルホニルオキシなどの基を；アリールチオアルキル基とは、たとえば、フェニルスルフェニルメチルおよび２−（ｐ−ニトロフェニルスルフェニル）エチルなどの基を；アリールスルホニルアルキル基とは、たとえば、ｐ−トルエンスルホニルエチルなどの基を；アルキルスルホニルアミノ基とは、たとえば、メチルスルホニルアミノおよびエチルスルホニルアミノなどのＣ１−６アルキルスルホニルアミノ基を意味する。Acyloxy groups are, for example, linear or branched C 2-6 alkanoyloxy groups such as acetoxy and propionyloxy, and aroyloxy groups such as benzoyloxy; acylalkyl groups are, for example, acetylmethyl, benzoyl Groups such as methyl, p-nitrobenzoylmethyl, p-bromobenzoylmethyl, p-methoxybenzoylmethyl and 1-benzoylethyl; acyloxyalkyl groups include, for example, acetoxymethyl, propionyloxymethyl and pivaloyloxymethyl the groups; and alkylthio groups such as methylthio, a C 1-6 alkylthio group such as ethylthio and propylthio; the alkylthioalkyl group, for example, methylthiomethyl, ethylthiomethyl and propyl The arylthio group, for example, a group such as phenylthio; a C 1-6 alkylthio C 1-6 alkyl group such as thiomethyl The alkylsulfonyl group, for example, C, such as methylsulfonyl, ethylsulfonyl and propylsulfonyl 1- 6 alkylsulfonyl group; an arylsulfonyl group is a group such as benzenesulfonyl, toluenesulfonyl and naphthalenesulfonyl; an alkylsulfonyloxy group is a C 1-6 alkyl such as methylsulfonyloxy and ethylsulfonyloxy A sulfonyloxy group; an arylsulfonyloxy group, for example, a group such as benzenesulfonyloxy and toluenesulfonyloxy; an arylthioalkyl group, for example, phenylsulfenylmethyl And a group such as 2- (p-nitrophenylsulfenyl) ethyl; an arylsulfonylalkyl group such as p-toluenesulfonylethyl; an alkylsulfonylamino group such as methylsulfonylamino and ethyl Means a C 1-6 alkylsulfonylamino group such as sulfonylamino;
アルキルアミノ基とは、たとえば、メチルアミノ、エチルアミノ、プロピルアミノ、イソプロピルアミノ、ブチルアミノおよびヘキシルアミノなどのＣ１−６アルキルアミノ基を；ジアルキルアミノ基とは、たとえば、ジメチルアミノ、ジエチルアミノ、ジプロピルアミノ、ジブチルアミノおよび（メチル）（エチル）アミノなどの（Ｃ１−６アルキル）（Ｃ１−６アルキル）アミノ基を；アルカノイルアミノ基とは、たとえば、アセチルアミノ、プロピオニルアミノ、ブチリルアミノ、バレリルアミノおよびピバロイルアミノなどの（直鎖状または分枝鎖状のＣ２−６アルカノイル）アミノ基を意味する。An alkylamino group is, for example, a C 1-6 alkylamino group such as methylamino, ethylamino, propylamino, isopropylamino, butylamino and hexylamino; a dialkylamino group is, for example, dimethylamino, diethylamino, diamino (C 1-6 alkyl) (C 1-6 alkyl) amino group such as propylamino, dibutylamino and (methyl) (ethyl) amino; alkanoylamino group means, for example, acetylamino, propionylamino, butyrylamino, valerylamino And (linear or branched C 2-6 alkanoyl) amino groups such as pivaloylamino.
複素環式基とは、たとえば、単環の複素環式基、二環式の複素環式基および三環式の複素環式基を意味する。 The heterocyclic group means, for example, a monocyclic heterocyclic group, a bicyclic heterocyclic group, and a tricyclic heterocyclic group.
単環の複素環式基とは、たとえば、ピロリル、ピロリニル、ピロリジニル、ピペリジル、ピペラジニル、イミダゾリル、ピラゾリル、ピリジル、テトラヒドロピリジル、ピリダジニル、ピラジニル、ピリミジニル、テトラゾリル、イミダゾリニル、イミダゾリジニル、ピラゾリニルおよびピラゾリジニル基などの該環を形成する異項原子として窒素原子のみを含む単環の含窒素複素環式基；フリルおよびピラニル基などの該環を形成する異項原子として酸素原子のみを含む単環の含酸素複素環式基；チエニル基などの該環を形成する異項原子として硫黄原子のみを含む単環の含硫黄複素環式基；オキサゾリル、オキサジアゾリル、イソオキサゾリルおよびモルホリニル基などの該環を形成する異項原子として窒素原子および酸素原子のみを含む単環の含窒素・酸素複素環式基；チアゾリル、イソチアゾリル、チアジアゾリルおよびチオモルホリニル基などの該環を形成する異項原子として窒素原子および硫黄原子のみを含む単環の含窒素・硫黄複素環式基ならびにチオキサニル基などの該環を形成する異項原子として酸素原子および硫黄原子のみを含む単環の含酸素・硫黄複素環式基などを意味する。 Monocyclic heterocyclic groups include, for example, pyrrolyl, pyrrolinyl, pyrrolidinyl, piperidyl, piperazinyl, imidazolyl, pyrazolyl, pyridyl, tetrahydropyridyl, pyridazinyl, pyrazinyl, pyrimidinyl, tetrazolyl, imidazolinyl, imidazolidinyl, pyrazolinyl and pyrazolidinyl groups Monocyclic nitrogen-containing heterocyclic groups containing only nitrogen atoms as ring-forming hetero atoms; monocyclic oxygen-containing heterocyclic rings containing only oxygen atoms as ring-forming hetero atoms such as furyl and pyranyl groups A monocyclic sulfur-containing heterocyclic group containing only a sulfur atom as a hetero atom forming the ring such as a thienyl group; as a hetero atom forming the ring such as an oxazolyl, oxadiazolyl, isoxazolyl and morpholinyl group Contains only nitrogen and oxygen atoms Monocyclic nitrogen-containing / oxygen heterocyclic groups; monocyclic nitrogen-containing / sulfur heterocyclic groups containing only nitrogen and sulfur atoms as the hetero atoms forming the ring, such as thiazolyl, isothiazolyl, thiadiazolyl and thiomorpholinyl groups And a monocyclic oxygen-containing / sulfur heterocyclic group containing only an oxygen atom and a sulfur atom as the hetero atoms forming the ring, such as a thioxanyl group.
該環を形成する窒素原子を介して隣接する基と結合する単環の複素環式とは、ピロール−１−イル、ピロリン−１−イル、ピロリジン−１−イル、ピペリジン−１−イル、ピペラジン−１−イル、イミダゾール−１−イル、ピラゾール−１−イル、テトラゾール−１−イル、イミダゾリン−１−イル、イミダゾリジン−１−イル、ピラゾリン−１−イル、ピラゾリジン−１−イル、モルホリン−４−イルおよびチオモルホリン−４−イル基などの該環を形成する窒素原子を介して隣接する基と結合する単環の含窒素複素環式基を意味する。 A monocyclic heterocyclic group bonded to an adjacent group through a nitrogen atom forming the ring is pyrrol-1-yl, pyrrolin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, piperazine -1-yl, imidazol-1-yl, pyrazol-1-yl, tetrazol-1-yl, imidazolin-1-yl, imidazolidin-1-yl, pyrazolin-1-yl, pyrazolidin-1-yl, morpholine- The monocyclic nitrogen-containing heterocyclic group which couple | bonds with an adjacent group through the nitrogen atom which forms this ring, such as 4-yl and thiomorpholin-4-yl group.
二環式の複素環式基とは、インドリル、インドリニル、２−オキソインドリニル、イソインドリル、インドリジニル、ベンズイミダゾリル、ベンゾトリアゾリル、インダゾリル、キノリル、テトラヒドロキノリニル、テトラヒドロイソキノリニル、キノリジニル、イソキノリル、フタラジニル、ナフチリジニル、キノキサリニル、ジヒドロキノキサリニル、キナゾリニル、シンノリニル、キヌクリジニル、ピロロピリジルおよび２，３−ジヒドロベンゾピロリル基などの該環を形成する異項原子として１〜３個の窒素原子のみを含む縮合環または架橋環で示される二環式の含窒素複素環式基；ベンゾフラニル、イソベンゾフラニル、クロメニル、クロマニル、イソクロマニル、ベンゾ−１，３−ジオキソリル、ベンゾ−１,４−ジオキサニルおよび２，３−ジヒドロベンゾフラニル基などの該環を形成する異項原子として酸素原子のみを含む縮合環または架橋環で示される二環式の含酸素複素環式基；ベンゾチエニルおよび２，３−ジヒドロベンゾチエニル基などの該環を形成する異項原子として硫黄原子のみを含む縮合環または架橋環で示される二環式の含硫黄複素環式基；ベンゾモルホリニルおよびベンゾモルホロニル基などの該環を形成する異項原子として窒素原子および酸素原子を含む縮合環または架橋環で示される二環式の含窒素・酸素複素環式基ならびにベンゾチアゾリルおよびベンゾチアジアゾリル基などの該環を形成する異項原子として窒素原子および硫黄原子を含む縮合環または架橋環で示される二環式の含窒素・硫黄複素環式基を意味する。 Bicyclic heterocyclic groups include indolyl, indolinyl, 2-oxoindolinyl, isoindolyl, indolizinyl, benzimidazolyl, benzotriazolyl, indazolyl, quinolyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, quinolidinyl, Only 1 to 3 nitrogen atoms as hetero atoms forming the ring such as isoquinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, dihydroquinoxalinyl, quinazolinyl, cinnolinyl, quinuclidinyl, pyrrolopyridyl and 2,3-dihydrobenzopyrrolyl groups A bicyclic nitrogen-containing heterocyclic group represented by a condensed ring or a bridged ring containing: benzofuranyl, isobenzofuranyl, chromenyl, chromanyl, isochromanyl, benzo-1,3-dioxolyl, benzo-1,4-dioxanyl And a bicyclic oxygen-containing heterocyclic group represented by a condensed ring or a bridged ring containing only an oxygen atom as a hetero atom forming the ring, such as a 2,3-dihydrobenzofuranyl group; benzothienyl and 2, A bicyclic sulfur-containing heterocyclic group represented by a condensed ring or a bridged ring containing only a sulfur atom as a hetero atom forming the ring, such as a 3-dihydrobenzothienyl group; benzomorpholinyl and benzomorpholonyl A bicyclic nitrogen-containing / oxygen heterocyclic group represented by a condensed ring or a bridged ring containing a nitrogen atom and an oxygen atom as a hetero atom forming the ring, such as a group, and a benzothiazolyl and benzothiadiazolyl group It means a bicyclic nitrogen-containing / sulfur heterocyclic group represented by a condensed ring or a bridged ring containing a nitrogen atom and a sulfur atom as a hetero atom forming a ring.
該環を形成する窒素原子を介して隣接する基と結合する二環式の複素環式基とは、インドール−１−イル、インドリン−１−イル、イソインドール−２−イル、ベンズイミダゾール−１−イル、ベンゾトリアゾール−１−イル、ベンゾトリアゾール−２−イル、インダゾール−１−イル、ベンゾモルホリン−４−イル基などの該環を形成する窒素原子を介して隣接する基と結合する二環式の含窒素複素環式基を意味する。 The bicyclic heterocyclic group bonded to the adjacent group through the nitrogen atom forming the ring is indol-1-yl, indolin-1-yl, isoindol-2-yl, benzimidazole-1 Bicycles bonded to adjacent groups through the nitrogen atom forming the ring, such as -yl, benzotriazol-1-yl, benzotriazol-2-yl, indazol-1-yl, benzomorpholin-4-yl group Means a nitrogen-containing heterocyclic group of the formula
三環式の複素環式基とは、チアントレニル、キサンテニル、フェノキサチイニル、カルバゾリル、β−カルボリニル、フェナントリジニル、アクリジニル、ペリミジニル、フェナントロリニル、フェナジニル、フェノチアジニルおよびフェノキサジニルなどの三環式の複素環式基を意味する。 Tricyclic heterocyclic groups include trianthrenyl, xanthenyl, phenoxathiinyl, carbazolyl, β-carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl, phenazinyl, phenothiazinyl and phenoxazinyl. Means a heterocyclic group of formula
含酸素複素環式基とは、たとえば、２−テトラヒドロピラニルおよび２−テトラヒドロフラニルなどの基を；含硫黄複素環式基とは、たとえば、テトラヒドロチオピラニルなどの基を；複素環オキシカルボニル基とは、たとえば、２−フルフリルオキシカルボニル、８−キノリルオキシカルボニルなどの基を；含窒素複素環式アルキル基とは、たとえば、フタルイミドメチルおよびスクシンイミドメチルなどの基を；置換シリル基とは、たとえば、トリメチルシリル、トリエチルシリルおよびトリブチルシリルなどの基を；アルキルシリルアルキル基とは、たとえば、２−（トリメチルシリル）エチルなどの基を意味する。 The oxygen-containing heterocyclic group is, for example, a group such as 2-tetrahydropyranyl and 2-tetrahydrofuranyl; the sulfur-containing heterocyclic group is, for example, a group such as tetrahydrothiopyranyl; Examples of the group include groups such as 2-furfuryloxycarbonyl and 8-quinolyloxycarbonyl; examples of the nitrogen-containing heterocyclic alkyl group include groups such as phthalimidomethyl and succinimidomethyl; Is, for example, a group such as trimethylsilyl, triethylsilyl and tributylsilyl; an alkylsilylalkyl group is a group such as, for example, 2- (trimethylsilyl) ethyl.
複素環式アルキル基とは、たとえば、ピロリルメチル、ピペリジルメチル、ピペラジニルメチル、イミダゾリルメチル、ピリジルメチル、ピラジニルメチル、ピリミジニルメチル、フリルメチル、チエニルメチル、オキサゾリルメチル、イソオキサゾリルメチル、モルホリニルメチル、チアゾリルメチルおよびイソチアゾリルメチルなどの単環の複素環式Ｃ１−６アルキル基；インドリルメチル、インドリニルメチル、イソインドリルメチル、ベンズイミダゾリルメチル、ベンゾトリアゾリルメチル、キノリルメチル、キノリジニルメチル、イソキノリルメチル、ナフチリジニルメチル、キノキサリニルメチル、ベンゾフラニルメチル、ベンゾチエニルメチル、ベンゾモルホリニルメチル、ベンゾチアゾリルメチルおよびベンゾチアジアゾリルメチル基などの二環式の複素環式Ｃ１−６アルキル基；ならびにチアントレニルメチル、キサンテニルメチル、カルバゾリルメチル、フェノチアジニルメチルおよびフェノキサジニルメチルなどの三環式の複素環式Ｃ１−６アルキル基を意味する。Heterocyclic alkyl groups include, for example, pyrrolylmethyl, piperidylmethyl, piperazinylmethyl, imidazolylmethyl, pyridylmethyl, pyrazinylmethyl, pyrimidinylmethyl, furylmethyl, thienylmethyl, oxazolylmethyl, isoxazolylmethyl, morpholinyl Monocyclic heterocyclic C 1-6 alkyl groups such as nylmethyl, thiazolylmethyl and isothiazolylmethyl; indolylmethyl, indolinylmethyl, isoindolylmethyl, benzimidazolylmethyl, benzotriazolylmethyl, quinolylmethyl, quino Lydinylmethyl, isoquinolylmethyl, naphthyridinylmethyl, quinoxalinylmethyl, benzofuranylmethyl, benzothienylmethyl, benzomorpholinylmethyl, benzothiazolylmethyl and benzothiadiazoli Bicyclic heterocyclic C 1-6 alkyl groups such as rumethyl groups; and tricyclic heterocyclic groups such as thiantenylmethyl, xanthenylmethyl, carbazolylmethyl, phenothiazinylmethyl and phenoxazinylmethyl Means a C 1-6 alkyl group;
環状アミノ基とは、たとえば、飽和の環状アミノおよび不飽和の環状アミノ基のいずれでもよく、また当該環内にさらに１つまたはそれ以上の窒素原子、酸素原子、硫黄原子などの異種原子およびカルボニル炭素を含んでいてもよく、さらに単環であっても二環式または三環式であってもよく、さらに具体的には、アジリジン−１−イル、アゼチジン−１−イル、ピロリジン−１−イル、ピロリン−１−イル、ピロール−１−イル、ジヒドロピリジン−１−イル、テトラヒドロピリジン−１−イル、ピペリジン−１−イル、ジヒドロアゼピン−１−イルおよびペルヒドロアゼピン−１−イルなどの窒素原子１個を有する飽和または不飽和の単環式３〜７員の環状アミノ基；イミダゾール−１−イル、イミダゾリジン−１−イル、イミダゾリン−１−イル、ピラゾリジン−１−イル、ピペラジン−１−イル、１，４−ジヒドロピラジン−１−イル、１，２−ジヒドロピリミジン−１−イル、ペルヒドロピラジン−１−イルおよびホモピペラジン−１−イルなどの窒素原子２個を有する飽和または不飽和の単環式３〜７員の環状アミノ基；１，２，４−トリアゾール−１−イル、１，２，３−トリアゾール−１−イル、１，２−ジヒドロ−１，２，４−トリアジン−１−イルおよびペルヒドロ−Ｓ−トリアジン−１−イルなどの窒素原子３個以上を有する飽和または不飽和の単環式３〜７員の環状アミノ基；オキサゾリジン−３−イル、イソオキサゾリジン−２−イル、モルホリン−４−イル、チアゾリジン−３−イル、イソチアゾリジン−２−イル、チオモルホリン−４−イル、ホモチオモルホリン−４−イルおよび１，２，４−チアジアゾリン−２−イルなどの窒素原子以外に酸素原子および硫黄原子から選ばれるヘテロ原子１〜４個を有する飽和または不飽和の単環式３〜７員の環状アミノ基；イソインドリン−２−イル、インドリン−１−イル、１Ｈ−インダゾール−１−イル、１Ｈ−インドール−１−イル、１Ｈ−ベンズイミダゾール−１−イル、プリン−７−イル、テトラヒドロキノリン−１−イルおよびテトラヒドロイソキノリン−２−イルなどの飽和または不飽和の二環式または三環式の環状アミノ基；ならびに５−アザスピロ［２.４］ヘプタン−５−イル、２，８−ジアザビシクロ［４.３.０］ノナン−８−イル、３−アザビシクロ［３.１.０］ヘキサン−３−イル、２−オキサ−５，８−ジアザビシクロ［４.３.０］ノナン−８−イル、２，８−ジアザスピロ［４.４］ノナン−２−イルおよび７−アザビシクロ［２.２.１］ヘプタン−７−イルなどのスピロ式または架橋式の飽和または不飽和の５〜１２員の環状アミノ基を意味する。 The cyclic amino group may be, for example, either a saturated cyclic amino group or an unsaturated cyclic amino group, and one or more hetero atoms such as nitrogen atom, oxygen atom, sulfur atom and carbonyl in the ring. It may contain carbon and may be monocyclic, bicyclic or tricyclic, and more specifically, aziridin-1-yl, azetidin-1-yl, pyrrolidin-1- Nitrogen such as yl, pyrrolin-1-yl, pyrrol-1-yl, dihydropyridin-1-yl, tetrahydropyridin-1-yl, piperidin-1-yl, dihydroazepin-1-yl and perhydroazepin-1-yl Saturated or unsaturated monocyclic 3-7 membered cyclic amino group having 1 atom; imidazol-1-yl, imidazolidin-1-yl, imidazoline 1-yl, pyrazolidin-1-yl, piperazin-1-yl, 1,4-dihydropyrazin-1-yl, 1,2-dihydropyrimidin-1-yl, perhydropyrazin-1-yl and homopiperazine-1 A saturated or unsaturated monocyclic 3-7 membered cyclic amino group having two nitrogen atoms such as yl; 1,2,4-triazol-1-yl, 1,2,3-triazol-1-yl Saturated or unsaturated monocyclic 3 to 7 membered having 3 or more nitrogen atoms such as 1,2-dihydro-1,2,4-triazin-1-yl and perhydro-S-triazin-1-yl Cyclic amino group; oxazolidine-3-yl, isoxazolidine-2-yl, morpholin-4-yl, thiazolidin-3-yl, isothiazolidin-2-yl, thiomorpholin-4-yl, homo Saturated or unsaturated monocyclic 3 to 7 having 1 to 4 heteroatoms selected from oxygen and sulfur atoms in addition to nitrogen atoms such as morpholin-4-yl and 1,2,4-thiadiazolin-2-yl Membered cyclic amino group; isoindoline-2-yl, indoline-1-yl, 1H-indazol-1-yl, 1H-indol-1-yl, 1H-benzimidazol-1-yl, purin-7-yl, Saturated or unsaturated bicyclic or tricyclic cyclic amino groups such as tetrahydroquinolin-1-yl and tetrahydroisoquinolin-2-yl; and 5-azaspiro [2.4] heptan-5-yl, 2,8 -Diazabicyclo [4.3.0] nonane-8-yl, 3-azabicyclo [3.1.0] hexane-3-yl, 2-oxa-5,8-diazabicyclo [ .3.0] nonan-8-yl, 2,8-diazaspiro [4.4] nonan-2-yl and 7-azabicyclo [2.2.1] heptan-7-yl A saturated or unsaturated 5- to 12-membered cyclic amino group is meant.
アミノ保護基としては、通常のアミノ基の保護基として使用し得るすべての基を含み、たとえば、Ｗ．グリーン（W.Greene）ら、プロテクティブ・グループス・イン・オーガニック・シンセシス（Protective Groups in Organic Synthesis）第3版、1999年、p.494-615、ジョン・ウィリイ・アンド・サンズ社（John Wiley & Sons,INC.）に記載されている基が挙げられる。具体的には、たとえば、アシル基、アルキルオキシカルボニル基、アルアルキルオキシカルボニル基、アリールオキシカルボニル基、アルアルキル基、アルコキシアルキル基、アルアルキルオキシアルキル基、アリールチオ基、アルキルスルホニル基、アリールスルホニル基および置換シリル基などが挙げられる。 Amino protecting groups include all groups that can be used as protecting groups for ordinary amino groups. W. Greene et al., Protective Groups in Organic Synthesis, 3rd edition, 1999, p.494-615, John Wiley & Sons, INC.). Specifically, for example, acyl group, alkyloxycarbonyl group, aralkyloxycarbonyl group, aryloxycarbonyl group, aralkyl group, alkoxyalkyl group, aralkyloxyalkyl group, arylthio group, alkylsulfonyl group, arylsulfonyl group And substituted silyl groups.
イミノ保護基としては、通常のイミノ基の保護基として使用し得るすべての基を含み、たとえば、Ｗ．グリーン（W.Greene）ら、プロテクティブ・グループス・イン・オーガニック・シンセシス（Protective Groups in Organic Synthesis）第3版、1999年、p.494-615、ジョン・ウィリイ・アンド・サンズ社（John Wiley & Sons,INC.）に記載されている基が挙げられる。具体的には、たとえば、アシル基、アルキルオキシカルボニル基、アルアルキルオキシカルボニル基、アリールオキシカルボニル基、アルアルキル基、アルコキシアルキル基、アリールチオ基、アルキルスルホニル基、アリールスルホニル基および置換シリル基などが挙げられる。 The imino protecting group includes all groups that can be used as protecting groups for ordinary imino groups. W. Greene et al., Protective Groups in Organic Synthesis, 3rd edition, 1999, p.494-615, John Wiley & Sons, INC.). Specific examples include an acyl group, an alkyloxycarbonyl group, an aralkyloxycarbonyl group, an aryloxycarbonyl group, an aralkyl group, an alkoxyalkyl group, an arylthio group, an alkylsulfonyl group, an arylsulfonyl group, and a substituted silyl group. Can be mentioned.
アルキルアミノ保護基としては、通常のアルキルアミノ基の保護基として使用し得るすべての基を含み、たとえば、Ｗ．グリーン（W.Greene）ら、プロテクティブ・グループス・イン・オーガニック・シンセシス（Protective Groups in Organic Synthesis）第3版、1999年、p.494-615、ジョン・ウィリイ・アンド・サンズ社（John Wiley & Sons,INC.）に記載されている基が挙げられる。具体的には、たとえば、アシル基、アルキルオキシカルボニル基、アルアルキルオキシカルボニル基、アリールオキシカルボニル基、アルアルキル基、アルコキシアルキル基、アリールチオ基、アルキルスルホニル基、アリールスルホニル基および置換シリル基などが挙げられる。 Alkylamino protecting groups include all groups that can be used as protecting groups for conventional alkylamino groups. W. Greene et al., Protective Groups in Organic Synthesis, 3rd edition, 1999, p.494-615, John Wiley & Sons, INC.). Specific examples include an acyl group, an alkyloxycarbonyl group, an aralkyloxycarbonyl group, an aryloxycarbonyl group, an aralkyl group, an alkoxyalkyl group, an arylthio group, an alkylsulfonyl group, an arylsulfonyl group, and a substituted silyl group. Can be mentioned.
ヒドロキシル保護基としては、通常のヒドロキシル基の保護基として使用し得るすべての基を含み、たとえば、Ｗ．グリーン（W.Greene）ら、プロテクティブ・グループス・イン・オーガニック・シンセシス（Protective Groups in Organic Synthesis）第3版、1999年、p.17-245、ジョン・ウィリイ・アンド・サンズ社（John Wiley & Sons,INC.）に記載されている基が挙げられる。具体的には、たとえば、アシル基、アルキルオキシカルボニル基、アルアルキルオキシカルボニル基、複素環オキシカルボニル基、アルキル基、アルケニル基、アルアルキル基、含酸素複素環式基、含硫黄複素環式基、アルコキシアルキル基、アルアルキルオキシアルキル基、アルキルスルホニル基、アリールスルホニル基および置換シリル基などが挙げられる。 Hydroxyl protecting groups include all groups that can be used as protecting groups for conventional hydroxyl groups. W. Greene et al., Protective Groups in Organic Synthesis, 3rd Edition, 1999, p.17-245, John Wiley & Sons (John Wiley & Sons, INC.). Specifically, for example, acyl group, alkyloxycarbonyl group, aralkyloxycarbonyl group, heterocyclic oxycarbonyl group, alkyl group, alkenyl group, aralkyl group, oxygen-containing heterocyclic group, sulfur-containing heterocyclic group , An alkoxyalkyl group, an aralkyloxyalkyl group, an alkylsulfonyl group, an arylsulfonyl group, and a substituted silyl group.
カルボキシル保護基としては、通常のカルボキシル基の保護基として使用し得るすべての基を含み、たとえば、Ｗ．グリーン（W.Greene）ら、プロテクティブ・グループス・イン・オーガニック・シンセシス（Protective Groups in Organic Synthesis）第3版、1999年、p.369-453、ジョン・ウィリイ・アンド・サンズ社（John Wiley & Sons,INC.）に記載されている基が挙げられる。具体的には、たとえば、アルキル基、アリール基、アルアルキル基、アシルアルキル基、アリールチオアルキル基、アリールスルホニルアルキル基、含酸素複素環式基、アルキルシリルアルキル基、アシルオキシアルキル基、含窒素複素環式アルキル基、シクロアルキル基、アルコキシアルキル基、アルアルキルオキシアルキル基、アルキルチオアルキル基、アルケニル基ならびに置換シリル基などが挙げられる。 The carboxyl protecting group includes all groups that can be used as protecting groups for ordinary carboxyl groups. W. Greene et al., Protective Groups in Organic Synthesis, 3rd Edition, 1999, p.369-453, John Wiley & Sons (John Wiley & Sons, INC.). Specifically, for example, alkyl group, aryl group, aralkyl group, acylalkyl group, arylthioalkyl group, arylsulfonylalkyl group, oxygen-containing heterocyclic group, alkylsilylalkyl group, acyloxyalkyl group, nitrogen-containing complex Examples include cyclic alkyl groups, cycloalkyl groups, alkoxyalkyl groups, aralkyloxyalkyl groups, alkylthioalkyl groups, alkenyl groups, and substituted silyl groups.
フェノール性ヒドロキシル保護基としては、通常のフェノール性ヒドロキシル基の保護基として使用し得るすべての基を含み、たとえば、Ｗ．グリーン（W.Greene）ら、プロテクティブ・グループス・イン・オーガニック・シンセシス（Protective Groups in Organic Synthesis）第3版、1999年、p.246-287、ジョン・ウィリイ・アンド・サンズ社（John Wiley & Sons,INC.）に記載されている基が挙げられる。具体的には、たとえば、アシル基、アルキル基、アルケニル基、アルアルキル基、含酸素複素環式基、含硫黄複素環式基、アルコキシアルキル基、アルキルスルホニル基、アリールスルホニル基および置換シリル基などが挙げられる。 The phenolic hydroxyl protecting group includes all groups that can be used as protecting groups for ordinary phenolic hydroxyl groups. W. Greene et al., Protective Groups in Organic Synthesis, 3rd edition, 1999, p.246-287, John Wiley & Sons (John Wiley & Sons, INC.). Specifically, for example, acyl group, alkyl group, alkenyl group, aralkyl group, oxygen-containing heterocyclic group, sulfur-containing heterocyclic group, alkoxyalkyl group, alkylsulfonyl group, arylsulfonyl group, substituted silyl group, etc. Is mentioned.
脱離基としては、たとえば、ハロゲン原子、アルキルスルホニルオキシ基およびアリールスルホニルオキシ基などが挙げられる。 Examples of the leaving group include a halogen atom, an alkylsulfonyloxy group, and an arylsulfonyloxy group.
一般式［１］の化合物の塩としては、通常知られているアミノ基などの塩基性基またはフェノール性ヒドロキシル基もしくはカルボキシル基などの酸性基における塩を挙げることができる。
塩基性基における塩としては、たとえば、塩酸、臭化水素および硫酸などの鉱酸との塩；酒石酸、ギ酸、酢酸、クエン酸、トリクロロ酢酸およびトリフルオロ酢酸などの有機カルボン酸との塩ならびにメタンスルホン酸、ベンゼンスルホン酸、ｐ−トルエンスルホン酸、メシチレンスルホン酸およびナフタレンスルホン酸などのスルホン酸との塩などが挙げられる。
酸性基における塩としては、たとえば、ナトリウムおよびカリウムなどのアルカリ金属との塩；カルシウムおよびマグネシウムなどのアルカリ土類金属との塩；アンモニウム塩ならびにトリメチルアミン、トリエチルアミン、トリブチルアミン、ピリジン、Ｎ，Ｎ−ジメチルアニリン、Ｎ−メチルピペリジン、Ｎ−メチルモルホリン、ジエチルアミン、ジシクロヘキシルアミン、プロカイン、ジベンジルアミン、Ｎ−ベンジル−β−フェネチルアミンおよびＮ，Ｎ’−ジベンジルエチレンジアミンなどの含窒素有機塩基との塩などを挙げることができる。
さらに、上記、塩の中で一般式［１］の化合物の好ましい塩としては、薬理学的に許容される塩が挙げられる。Examples of the salt of the compound represented by the general formula [1] include a conventionally known salt in a basic group such as an amino group or an acidic group such as a phenolic hydroxyl group or a carboxyl group.
Salts in basic groups include, for example, salts with mineral acids such as hydrochloric acid, hydrogen bromide and sulfuric acid; salts with organic carboxylic acids such as tartaric acid, formic acid, acetic acid, citric acid, trichloroacetic acid and trifluoroacetic acid, and methane Examples thereof include salts with sulfonic acids such as sulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, mesitylenesulfonic acid and naphthalenesulfonic acid.
Examples of the salt in the acidic group include salts with alkali metals such as sodium and potassium; salts with alkaline earth metals such as calcium and magnesium; ammonium salts and trimethylamine, triethylamine, tributylamine, pyridine, N, N-dimethyl. Salts with nitrogen-containing organic bases such as aniline, N-methylpiperidine, N-methylmorpholine, diethylamine, dicyclohexylamine, procaine, dibenzylamine, N-benzyl-β-phenethylamine and N, N′-dibenzylethylenediamine, etc. Can be mentioned.
Furthermore, among the above salts, preferred salts of the compound of the general formula [1] include pharmacologically acceptable salts.
本発明におけるＲ１のアルキル基、アルケニル基、アルキニル基およびシクロアルキル基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、スルホ基、ホスホリル基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基、ハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、シクロアルキル、シクロアルケニル、アリール、環状アミノ、アルアルキルおよび複素環式基ならびにオキソ基などから選ばれる１つ以上の基で置換されていてもよい。好ましい置換基としては、ハロゲン原子、低級アルキル基および低級アルコキシ基から選ばれる１つ以上の基が挙げられる。In the present invention, the alkyl group, alkenyl group, alkynyl group and cycloalkyl group of R 1 are a halogen atom, a cyano group, a nitro group, an acyl group, a sulfo group, a phosphoryl group, an alkylsulfonyl group, an alkylsulfonylamino group, and an alkanoylamino group. , A carbamoyl group, an optionally protected carboxyl group, an optionally protected amino group, an optionally protected hydroxyl group, an alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl optionally substituted with a halogen atom , Cycloalkenyl, aryl, cyclic amino, aralkyl and heterocyclic groups and one or more groups selected from oxo groups and the like. Preferred substituents include one or more groups selected from a halogen atom, a lower alkyl group and a lower alkoxy group.
本発明におけるＲ２のアルキル基、アルケニル基、アルキニル基、シクロアルキル基、シクロアルケニル基、アリール基、アルアルキル基、複素環式基および複素環式アルキル基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、アシルオキシ基、スルホ基、ホスホリル基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基、ハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、シクロアルキル、シクロアルケニル、アリール、環状アミノ、アルアルキルおよび複素環式基ならびにオキソ基から選ばれる１つ以上の基で置換されていてもよい。好ましい置換基としては、ハロゲン原子、低級アルキル基および低級アルコキシ基から選ばれる１つ以上の基が挙げられる。In the present invention, the alkyl group, alkenyl group, alkynyl group, cycloalkyl group, cycloalkenyl group, aryl group, aralkyl group, heterocyclic group and heterocyclic alkyl group represented by R 2 are each a halogen atom, a cyano group or a nitro group. , Acyl group, acyloxy group, sulfo group, phosphoryl group, alkylsulfonyl group, alkylsulfonylamino group, alkanoylamino group, carbamoyl group, optionally protected carboxyl group, optionally protected amino group, protected One or more selected from an optionally substituted hydroxyl group, an optionally substituted alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, aryl, cyclic amino, aralkyl and heterocyclic group and an oxo group It may be substituted with a group. Preferred substituents include one or more groups selected from a halogen atom, a lower alkyl group and a lower alkoxy group.
本発明におけるＲ３のシクロアルキル基、シクロアルケニル基、アリール基および複素環式基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、アシルオキシ基、スルホ基、ホスホリル基、アルキルチオ基、アルキルアミノ基、ジアルキルアミノ基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、ヒドロキシアルキル基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基、保護されていてもよいカルボキシル基で置換されているアルコキシ基、ハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、シクロアルキル、シクロアルケニル、アリール、アリールオキシ、環状アミノ、アルアルキルおよび複素環式基ならびにオキソ基から選ばれる１つ以上の基で置換されていてもよい。好ましい置換基としては、ハロゲン原子、ニトロ基、アシル基、アルキルチオ基、アルキルアミノ基、ジアルキルアミノ基、ヒドロキシアルキル基、カルボキシル基、アミノ基、ヒドロキシル基、カルボキシル基で置換されているアルコキシ基ならびにハロゲン原子で置換されていてもよいアルキル、アルケニル、アルコキシ、シクロアルキル、アリール、環状アミノおよび複素環式基から選ばれる１つ以上の基が挙げられる。より好ましい置換基としては、ハロゲン原子、ニトロ基、アルキルチオ基、アルキルアミノ基、ジアルキルアミノ基、ヒドロキシアルキル基、カルボキシル基、アミノ基、ヒドロキシル基、カルボキシル基で置換されているアルコキシ基、アルケニル基、シクロアルキル基、アリール基、環状アミノ基ならびにハロゲン原子で置換されていてもよい低級アルキルおよび低級アルコキシ基から選ばれる１つ以上の基が挙げられる。よりさらに好ましい置換基としては、ハロゲン原子、低級アルキル基および低級アルコキシ基から選ばれる１つ以上の基が挙げられる。In the present invention, the cycloalkyl group, cycloalkenyl group, aryl group and heterocyclic group of R 3 are a halogen atom, cyano group, nitro group, acyl group, acyloxy group, sulfo group, phosphoryl group, alkylthio group, alkylamino group. , Dialkylamino group, alkylsulfonyl group, alkylsulfonylamino group, alkanoylamino group, hydroxyalkyl group, carbamoyl group, optionally protected carboxyl group, optionally protected amino group, optionally protected hydroxyl group Group, alkoxy group substituted by an optionally protected carboxyl group, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, aryl, aryloxy, cyclic amino, alkyl optionally substituted by a halogen atom Alkyl And may be substituted with one or more groups selected from a heterocyclic group and an oxo group. Preferred substituents include halogen atoms, nitro groups, acyl groups, alkylthio groups, alkylamino groups, dialkylamino groups, hydroxyalkyl groups, carboxyl groups, amino groups, hydroxyl groups, alkoxy groups substituted with carboxyl groups, and halogens. Examples thereof include one or more groups selected from alkyl, alkenyl, alkoxy, cycloalkyl, aryl, cyclic amino, and heterocyclic group which may be substituted with an atom. More preferred substituents include halogen atoms, nitro groups, alkylthio groups, alkylamino groups, dialkylamino groups, hydroxyalkyl groups, carboxyl groups, amino groups, hydroxyl groups, alkoxy groups substituted with carboxyl groups, alkenyl groups, Examples thereof include one or more groups selected from a cycloalkyl group, an aryl group, a cyclic amino group, and a lower alkyl and lower alkoxy group which may be substituted with a halogen atom. More preferable substituents include one or more groups selected from a halogen atom, a lower alkyl group, and a lower alkoxy group.
本発明におけるＲ４のシクロアルキル基、シクロアルケニル基、アリール基および複素環式基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、アシルオキシ基、スルホ基、ホスホリル基、アルキルチオ基、ジアルキルアミノ基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、ヒドロキシアルキル基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいアルキルアミノ基、保護されていてもよいヒドロキシル基、保護されていてもよいカルボキシル基で置換されているアルコキシ基、ハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、シクロアルキル、シクロアルケニル、アリール、アリールオキシ、環状アミノ、アルアルキルおよび複素環式基ならびにオキソ基から選ばれる１つ以上の基で置換されていてもよい。好ましい置換基としては、ハロゲン原子、ニトロ基、アシル基、アルキルチオ基、アルキルアミノ基、ジアルキルアミノ基、ヒドロキシアルキル基、カルボキシル基、アミノ基、ヒドロキシル基、カルボキシル基で置換されているアルコキシ基ならびにハロゲン原子で置換されていてもよいアルキル、アルケニル、アルコキシ、シクロアルキル、アリール、環状アミノおよび複素環式基から選ばれる１つ以上の基が挙げられる。より好ましい置換基としては、ハロゲン原子、ニトロ基、アシル基、アルキルアミノ基、ジアルキルアミノ基、ヒドロキシアルキル基、アミノ基、ヒドロキシル基、アルキル基およびアルコキシ基から選ばれる１つ以上の基が挙げられる。よりさらに好ましい置換基としては、ハロゲン原子、低級アルキル基および低級アルコキシ基から選ばれる１つ以上の基が挙げられる。The cycloalkyl group, cycloalkenyl group, aryl group and heterocyclic group of R 4 in the present invention are a halogen atom, a cyano group, a nitro group, an acyl group, an acyloxy group, a sulfo group, a phosphoryl group, an alkylthio group, a dialkylamino group. , Alkylsulfonyl group, alkylsulfonylamino group, alkanoylamino group, hydroxyalkyl group, carbamoyl group, optionally protected carboxyl group, optionally protected amino group, optionally protected alkylamino group, protection An optionally substituted hydroxyl group, an alkoxy group substituted with an optionally protected carboxyl group, an alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, aryl, aryl optionally substituted with a halogen atom Oxy, cyclic It may be substituted with one or more groups selected from amino, aralkyl and heterocyclic groups and oxo groups. Preferred substituents include halogen atoms, nitro groups, acyl groups, alkylthio groups, alkylamino groups, dialkylamino groups, hydroxyalkyl groups, carboxyl groups, amino groups, hydroxyl groups, alkoxy groups substituted with carboxyl groups, and halogens. Examples thereof include one or more groups selected from alkyl, alkenyl, alkoxy, cycloalkyl, aryl, cyclic amino, and heterocyclic group which may be substituted with an atom. More preferred substituents include one or more groups selected from halogen atoms, nitro groups, acyl groups, alkylamino groups, dialkylamino groups, hydroxyalkyl groups, amino groups, hydroxyl groups, alkyl groups and alkoxy groups. . More preferable substituents include one or more groups selected from a halogen atom, a lower alkyl group, and a lower alkoxy group.
本発明におけるＲ５のアルキル基およびアルコキシ基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、スルホ基、ホスホリル基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基、ハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、アリール、環状アミノ、アルアルキルおよび複素環式基から選ばれる１つ以上の基で置換されていてもよい。好ましい置換基としては、ハロゲン原子、低級アルキル基および低級アルコキシ基から選ばれる１つ以上の基が挙げられる。The alkyl group and alkoxy group of R 5 in the present invention are a halogen atom, cyano group, nitro group, acyl group, sulfo group, phosphoryl group, alkylsulfonyl group, alkylsulfonylamino group, alkanoylamino group, carbamoyl group, protected. An optionally protected carboxyl group, an optionally protected amino group, an optionally protected hydroxyl group, an optionally substituted alkyl, alkenyl, alkynyl, alkoxy, aryl, cyclic amino, aralkyl and heterocyclic It may be substituted with one or more groups selected from cyclic groups. Preferred substituents include one or more groups selected from a halogen atom, a lower alkyl group and a lower alkoxy group.
本発明におけるＸ１のアルキレン基、アルケニレン基、アルキニレン基およびシクロアルキレン基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、スルホ基、ホスホリル基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基ならびにハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、アリール、環状アミノ、アルアルキルおよび複素環式基から選ばれる１つ以上の基で置換されていてもよい。好ましい置換基としては、ハロゲン原子、低級アルキル基および低級アルコキシ基から選ばれる１つ以上の基が挙げられる。In the present invention, the alkylene group, alkenylene group, alkynylene group and cycloalkylene group represented by X 1 are a halogen atom, a cyano group, a nitro group, an acyl group, a sulfo group, a phosphoryl group, an alkylsulfonyl group, an alkylsulfonylamino group, and an alkanoylamino group. , A carbamoyl group, an optionally protected carboxyl group, an optionally protected amino group, an optionally protected hydroxyl group, and an alkyl, alkenyl, alkynyl, alkoxy, aryl, optionally substituted with a halogen atom, It may be substituted with one or more groups selected from cyclic amino, aralkyl and heterocyclic groups. Preferred substituents include one or more groups selected from a halogen atom, a lower alkyl group and a lower alkoxy group.
本発明におけるＹ１のアルキレン基、アルケニレン基およびアルキニレン基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、スルホ基、ホスホリル基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基ならびにハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、アリール、環状アミノ、アルアルキルおよび複素環式基から選ばれる１つ以上の基で置換されていてもよい。好ましい置換基としては、ハロゲン原子、低級アルキル基および低級アルコキシ基から選ばれる１つ以上の基が挙げられる。The alkylene group, alkenylene group and alkynylene group of Y 1 in the present invention are each a halogen atom, cyano group, nitro group, acyl group, sulfo group, phosphoryl group, alkylsulfonyl group, alkylsulfonylamino group, alkanoylamino group, carbamoyl group, An optionally protected carboxyl group, an optionally protected amino group, an optionally protected hydroxyl group, and an alkyl, alkenyl, alkynyl, alkoxy, aryl, cyclic amino, alkyl optionally substituted with a halogen atom It may be substituted with one or more groups selected from alkyl and heterocyclic groups. Preferred substituents include one or more groups selected from a halogen atom, a lower alkyl group and a lower alkoxy group.
本発明におけるＲ６のアルキル基およびアルコキシ基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、スルホ基、ホスホリル基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基ならびにハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、アリール、環状アミノ、アルアルキルおよび複素環式基から選ばれる１つ以上の基で置換されていてもよい。好ましい置換基としては、ハロゲン原子、低級アルキル基および低級アルコキシ基から選ばれる１つ以上の基が挙げられる。The alkyl group and alkoxy group of R 6 in the present invention are a halogen atom, cyano group, nitro group, acyl group, sulfo group, phosphoryl group, alkylsulfonyl group, alkylsulfonylamino group, alkanoylamino group, carbamoyl group, protected. An optionally protected carboxyl group, an optionally protected amino group, an optionally protected hydroxyl group, and an alkyl, alkenyl, alkynyl, alkoxy, aryl, cyclic amino, aralkyl and heterocycle optionally substituted with a halogen atom. It may be substituted with one or more groups selected from cyclic groups. Preferred substituents include one or more groups selected from a halogen atom, a lower alkyl group and a lower alkoxy group.
本発明におけるＲ７のアルキル基およびアルコキシ基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、スルホ基、ホスホリル基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基ならびにハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、アリール、環状アミノ、アルアルキルおよび複素環式基から選ばれる１つ以上の基で置換されていてもよい。好ましい置換基としては、ハロゲン原子、低級アルキル基および低級アルコキシ基から選ばれる１つ以上の基が挙げられる。The alkyl group and alkoxy group of R 7 in the present invention are a halogen atom, cyano group, nitro group, acyl group, sulfo group, phosphoryl group, alkylsulfonyl group, alkylsulfonylamino group, alkanoylamino group, carbamoyl group, protected. An optionally protected carboxyl group, an optionally protected amino group, an optionally protected hydroxyl group, and an alkyl, alkenyl, alkynyl, alkoxy, aryl, cyclic amino, aralkyl and heterocycle optionally substituted with a halogen atom. It may be substituted with one or more groups selected from cyclic groups. Preferred substituents include one or more groups selected from a halogen atom, a lower alkyl group and a lower alkoxy group.
本発明におけるＲ１およびＲ７が、一緒になって形成されるＣ２−４アルキレン基およびＣ２−４アルケニレン基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、スルホ基、ホスホリル基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基ならびにハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、アリール、環状アミノ、アルアルキルおよび複素環式基から選ばれる１つ以上の基で置換されていてもよい。好ましい置換基としては、ハロゲン原子、低級アルキル基および低級アルコキシ基から選ばれる１つ以上の基が挙げられる。The C 2-4 alkylene group and the C 2-4 alkenylene group formed by R 1 and R 7 in the present invention together are a halogen atom, a cyano group, a nitro group, an acyl group, a sulfo group, a phosphoryl group, Substituted with an alkylsulfonyl group, an alkylsulfonylamino group, an alkanoylamino group, a carbamoyl group, an optionally protected carboxyl group, an optionally protected amino group, an optionally protected hydroxyl group, and a halogen atom; It may be substituted with one or more groups selected from alkyl, alkenyl, alkynyl, alkoxy, aryl, cyclic amino, aralkyl and heterocyclic groups. Preferred substituents include one or more groups selected from a halogen atom, a lower alkyl group and a lower alkoxy group.
本発明化合物において、好ましい化合物としては、以下の化合物が挙げられる。
Ｒ１が、水素原子または置換されていてもよいアルキルもしくはシクロアルキル基である化合物が好ましく、置換されていてもよい低級アルキル基である化合物がより好ましく、低級アルキル基である化合物がさらに好ましい。
Ｒ２が、置換されていてもよいアルキル、シクロアルキル、アリール、アルアルキルまたは複素環式基である化合物が好ましく、置換されていてもよいアルキル、シクロアルキルまたは単環の複素環式基である化合物がより好ましく、置換されていてもよい低級アルキル基である化合物がさらに好ましく、低級アルキル基である化合物がよりさらに好ましい。
Ｒ３が、置換されていてもよいシクロアルキル、アリールまたは複素環式基である化合物が好ましく、置換されていてもよいアリールまたは複素環式基である化合物がより好ましく、置換されていてもよいフェニル、単環の複素環式または二環式の複素環式基である化合物がさらに好ましく、置換されていてもよいフェニル基または二環式の含酸素複素環式基である化合物がよりさらに好ましい。
また、Ｒ３が、ハロゲン原子、アルキルアミノ基、ジアルキルアミノ基、保護されていてもよいヒドロキシル基、ハロゲン原子で置換されていてもよいアルキル基およびハロゲン原子で置換されていてもよいアルコキシ基から選ばれる１つ以上の基で置換されていてもよいフェニル、単環の複素環式または二環式の含酸素複素環式基である化合物が好ましく、ハロゲン原子、ジアルキルアミノ基、ヒドロキシル基、低級アルキル基およびハロゲン原子で置換されていてもよいアルコキシ基から選ばれる１つ以上の基で置換されていてもよいフェニルまたは二環式の含酸素複素環式基である化合物がより好ましい。
Ｒ４が、置換されていてもよいシクロアルキル、アリールまたは複素環式基である化合物が好ましく、置換されていてもよいアリールまたは複素環式基である化合物がより好ましく、置換されていてもよいフェニルまたは単環の複素環式基である化合物がさらに好ましく、置換されていてもよいフェニル基である化合物がよりさらに好ましい。
また、Ｒ４が、ハロゲン原子、ニトロ基、アルキルアミノ基、ジアルキルアミノ基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基、ハロゲン原子で置換されていてもよいアルキル基およびハロゲン原子で置換されていてもよいアルコキシ基から選ばれる１つ以上の基で置換されていてもよいフェニルまたは単環の複素環式基である化合物がさらに好ましく、ハロゲン原子、アルキルアミノ基、ジアルキルアミノ基、アミノ基、ヒドロキシル基、低級アルキル基およびハロゲン原子で置換されていてもよいアルコキシ基から選ばれる１つ以上の基で置換されていてもよいフェニル基である化合物がよりさらに好ましい。
Ｒ５が、水素原子、ハロゲン原子、保護されていてもよいヒドロキシル基または置換されていてもよいアルキルもしくはアルコキシ基である化合物が好ましく、水素原子、ハロゲン原子、ヒドロキシル基、低級アルキル基または低級アルコキシ基である化合物がより好ましく、水素原子、ハロゲン原子またはヒドロキシル基である化合物がさらに好ましく、水素原子である化合物がよりさらに好ましい。In the compound of the present invention, preferred compounds include the following compounds.
A compound in which R 1 is a hydrogen atom or an optionally substituted alkyl or cycloalkyl group is preferred, a compound that is an optionally substituted lower alkyl group is more preferred, and a compound that is a lower alkyl group is more preferred.
A compound in which R 2 is an optionally substituted alkyl, cycloalkyl, aryl, aralkyl or heterocyclic group is preferred, and is an optionally substituted alkyl, cycloalkyl or monocyclic heterocyclic group Compounds are more preferred, compounds that are optionally substituted lower alkyl groups are more preferred, and compounds that are lower alkyl groups are even more preferred.
A compound in which R 3 is an optionally substituted cycloalkyl, aryl or heterocyclic group is preferred, a compound in which an optionally substituted aryl or heterocyclic group is preferred, and an optionally substituted More preferred are compounds that are phenyl, monocyclic heterocyclic or bicyclic heterocyclic groups, and even more preferred are compounds that are optionally substituted phenyl groups or bicyclic oxygen-containing heterocyclic groups. .
R 3 is a halogen atom, an alkylamino group, a dialkylamino group, a hydroxyl group that may be protected, an alkyl group that may be substituted with a halogen atom, or an alkoxy group that may be substituted with a halogen atom. Preferred is a compound which is a phenyl, monocyclic heterocyclic or bicyclic oxygen-containing heterocyclic group optionally substituted with one or more selected groups, and is a halogen atom, dialkylamino group, hydroxyl group, lower group More preferred is a compound which is phenyl or a bicyclic oxygen-containing heterocyclic group which may be substituted with one or more groups selected from an alkyl group and an alkoxy group which may be substituted with a halogen atom.
A compound in which R 4 is an optionally substituted cycloalkyl, aryl, or heterocyclic group is preferable, and a compound in which R 4 is an optionally substituted aryl or heterocyclic group is more preferable, and may be substituted. A compound that is phenyl or a monocyclic heterocyclic group is more preferable, and a compound that is an optionally substituted phenyl group is further more preferable.
R 4 represents a halogen atom, a nitro group, an alkylamino group, a dialkylamino group, an amino group which may be protected, a hydroxyl group which may be protected, an alkyl group which may be substituted with a halogen atom, and More preferably, the compound is a phenyl or monocyclic heterocyclic group optionally substituted with one or more groups selected from an alkoxy group optionally substituted with a halogen atom, a halogen atom, an alkylamino group, a dialkyl More preferred is a compound which is a phenyl group optionally substituted with one or more groups selected from an amino group, an amino group, a hydroxyl group, a lower alkyl group and an alkoxy group optionally substituted with a halogen atom.
R 5 is preferably a hydrogen atom, a halogen atom, an optionally protected hydroxyl group, or an optionally substituted alkyl or alkoxy group, preferably a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group or a lower alkoxy The compound which is a group is more preferable, the compound which is a hydrogen atom, a halogen atom or a hydroxyl group is more preferable, and the compound which is a hydrogen atom is still more preferable.
Ｘ１が、置換されていてもよいアルキレン、アルケニレンもしくはアルキニレン基または結合手である化合物が好ましく、結合手である化合物がより好ましい。
Ｘ２が、酸素原子または結合手である化合物が好ましく、結合手である化合物がより好ましい。
Ｙ１が、イミノ基、置換されていてもよいアルキレンもしくはアルケニレン基または結合手である化合物が好ましく、イミノ基または結合手である化合物がより好ましく、結合手である化合物がさらに好ましい。A compound in which X 1 is an optionally substituted alkylene, alkenylene or alkynylene group or a bond is preferable, and a compound in which a bond is a bond is more preferable.
A compound in which X 2 is an oxygen atom or a bond is preferable, and a compound in which X 2 is a bond is more preferable.
A compound in which Y 1 is an imino group, an optionally substituted alkylene or alkenylene group or a bond is preferable, a compound in which an imino group or a bond is present is more preferable, and a compound in which a bond is a bond is more preferable.
Ｚ１が、窒素原子またはＣＲ６ａ「式中、Ｒ６ａは、水素原子または置換されていてもよいアルコキシ基を示す。」である化合物が好ましく、窒素原子またはＣＲ６ｂ「式中、Ｒ６ｂは、水素原子または低級アルキル基を示す。」である化合物がより好ましく、窒素原子またはＣＨである化合物がさらに好ましく、ＣＨである化合物がよりさらに好ましい。
Ｚ２が、窒素原子またはＣＲ７ａ「式中、Ｒ７ａは、水素原子、ヒドロキシル基または置換されていてもよいアルキルもしくはアルコキシ基を示す。」である化合物が好ましく、窒素原子またはＣＲ７ｂ「式中、Ｒ７ｂは、水素原子、ヒドロキシル基、低級アルキル基または低級アルコキシ基を示す。」である化合物がより好ましく、窒素原子またはＣＨである化合物がさらに好ましく、ＣＨである化合物がよりさらに好ましい。
Ｒ１およびＲ７が、一緒になって、置換されていてもよいＣ２−４アルキレン基である化合物が好ましく、エチレンである化合物がより好ましい。A compound in which Z 1 is a nitrogen atom or CR 6a “wherein R 6a represents a hydrogen atom or an optionally substituted alkoxy group” is preferred, and a nitrogen atom or CR 6b “wherein R 6b is , Represents a hydrogen atom or a lower alkyl group. ”Is more preferred, a compound that is a nitrogen atom or CH is more preferred, and a compound that is CH is still more preferred.
A compound in which Z 2 is a nitrogen atom or CR 7a "wherein R 7a represents a hydrogen atom, a hydroxyl group or an optionally substituted alkyl or alkoxy group" is preferred, and a nitrogen atom or CR 7b "formula In the formula, R 7b represents a hydrogen atom, a hydroxyl group, a lower alkyl group or a lower alkoxy group. A compound represented by “is more preferable, a compound which is a nitrogen atom or CH is more preferable, and a compound which is CH is still more preferable.
A compound in which R 1 and R 7 together are an optionally substituted C 2-4 alkylene group is preferable, and a compound in which ethylene is ethylene is more preferable.
本発明化合物中、代表的化合物としては、たとえば、以下の表１〜６に記載の化合物が挙げられる。 Among the compounds of the present invention, representative compounds include, for example, compounds described in Tables 1 to 6 below.
次に、本発明化合物の製造法について説明する。
本発明化合物は、自体公知の方法を組み合わせることにより製造されるが、たとえば、次に示す製造法にしたがって製造することができる。Next, the manufacturing method of this invention compound is demonstrated.
The compound of the present invention is produced by combining methods known per se, and can be produced, for example, according to the production method shown below.
［製造法１］
一般式［１］の化合物は、塩基の存在下または不存在下、一般式［２］の化合物をハロゲン化スルホニルまたはスルホン酸無水物と反応させることにより製造することができる。
この反応で使用される溶媒としては、反応に悪影響を及ぼさないものであれば特に限定されないが、たとえば、Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミドおよび１−メチル−２−ピロリドンなどのアミド類；塩化メチレン、クロロホルムおよびジクロロエタンなどのハロゲン化炭化水素類；ベンゼン、トルエンおよびキシレンなどの芳香族炭化水素類；ジオキサン、テトラヒドロフラン、アニソール、エチレングリコールジメチルエーテル、ジエチレングリコールジメチルエーテルおよびジエチレングリコールジエチルエーテルなどのエーテル類；アセトニトリルなどのニトリル類；アセトンおよび２−ブタノンなどのケトン類；酢酸エチルおよび酢酸ブチルなどのエステル類；スルホランなどのスルホン類ならびにジメチルスルホキシドなどのスルホキシド類などが挙げられ、これらは混合して使用してもよい。The compound of the general formula [1] can be produced by reacting the compound of the general formula [2] with a sulfonyl halide or a sulfonic anhydride in the presence or absence of a base.
The solvent used in this reaction is not particularly limited as long as it does not adversely affect the reaction, and examples thereof include N, N-dimethylformamide, N, N-dimethylacetamide and 1-methyl-2-pyrrolidone. Amides; Halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; Aromatic hydrocarbons such as benzene, toluene and xylene; Ethers such as dioxane, tetrahydrofuran, anisole, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and diethylene glycol diethyl ether Nitriles such as acetonitrile; ketones such as acetone and 2-butanone; esters such as ethyl acetate and butyl acetate; sulfones such as sulfolane; Sulfoxide is like sulfoxides such as may be used in these mixed.
（１）ハロゲン化スルホニルを使用する場合
この反応に用いられるハロゲン化スルホニルとしては、たとえば、メタンスルホニルクロリド、ベンゼンスルホニルクロリドおよびα−トルエンスルホニルクロリドなどが挙げられる。また、ハロゲン化スルホニルは、対応するスルホン酸から、たとえば、新実験化学講座、1978年、第14巻、p.1784-1792、丸善に記載の方法またはそれに準じた方法で製造することができる。
ハロゲン化スルホニルの使用量は、一般式［２］の化合物に対して、1〜50倍モル、好ましくは、1〜5倍モルであればよい。
この反応において所望により用いられる塩基としては、たとえば、水素化ナトリウム、炭酸水素ナトリウム、炭酸ナトリウム、炭酸カリウム、炭酸セシウムおよびリン酸三カリウムなどの無機塩基ならびに酢酸ナトリウム、酢酸カリウム、ナトリウム＝ｔｅｒｔ−ブトキシド、ピリジン、４−（ジメチルアミノ）ピリジン、トリエチルアミン、ジイソプロピルエチルアミン、トリブチルアミンおよびＮ，Ｎ−ジシクロヘキシルメチルアミンなどの有機塩基が挙げられ、これらは混合して使用してもよい。塩基の使用量は、一般式［２］の化合物に対して1〜50倍モル、好ましくは、1〜5倍モルであればよい。
この反応は、通常、−78〜100℃、好ましくは、0〜80℃で10分間〜24時間実施すればよい。(1) When using sulfonyl halide Examples of the sulfonyl halide used in this reaction include methanesulfonyl chloride, benzenesulfonyl chloride, α-toluenesulfonyl chloride, and the like. The sulfonyl halide can be produced from the corresponding sulfonic acid by, for example, the method described in New Experimental Chemistry Course, 1978, Vol. 14, p.1784-1792, or Maruzen.
The amount of the sulfonyl halide used may be 1 to 50 times mol, preferably 1 to 5 times mol, of the compound of the general formula [2].
Bases optionally used in this reaction include, for example, inorganic bases such as sodium hydride, sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate and tripotassium phosphate, and sodium acetate, potassium acetate, sodium = tert-butoxide. , Pyridine, 4- (dimethylamino) pyridine, triethylamine, diisopropylethylamine, tributylamine and organic bases such as N, N-dicyclohexylmethylamine, which may be used in combination. The amount of the base used may be 1 to 50 times mol, preferably 1 to 5 times mol, of the compound of the general formula [2].
This reaction is usually carried out at −78 to 100 ° C., preferably 0 to 80 ° C. for 10 minutes to 24 hours.
（２）スルホン酸無水物を使用する場合
この反応に用いられるスルホン酸無水物としては、たとえば、無水メタンスルホン酸および無水トリフルオロメタンスルホン酸などが挙げられる。
スルホン酸無水物の使用量は、一般式［２］の化合物に対して、1〜50倍モル、好ましくは、1〜5倍モルであればよい。
この反応において所望により用いられる塩基としては、たとえば、炭酸水素ナトリウム、炭酸ナトリウム、炭酸カリウムおよび炭酸セシウムなどの無機塩基ならびにピリジン、４−（ジメチルアミノ）ピリジン、トリエチルアミンおよびジイソプロピルエチルアミンなどの有機塩基が挙げられ、これらは混合して使用してもよい。塩基の使用量は、一般式［２］の化合物に対して1〜50倍モル、好ましくは、1〜5倍モルであればよい。
この反応は、通常、−78〜100℃、好ましくは、0〜80℃で10分間〜24時間実施すればよい。(2) When using sulfonic acid anhydride Examples of the sulfonic acid anhydride used in this reaction include anhydrous methanesulfonic acid and anhydrous trifluoromethanesulfonic acid.
The usage-amount of a sulfonic acid anhydride should just be 1-50 times mole with respect to the compound of General formula [2], Preferably, it may be 1-5 times mole.
Examples of the base optionally used in this reaction include inorganic bases such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate and cesium carbonate, and organic bases such as pyridine, 4- (dimethylamino) pyridine, triethylamine and diisopropylethylamine. These may be used as a mixture. The amount of the base used may be 1 to 50 times mol, preferably 1 to 5 times mol, of the compound of the general formula [2].
This reaction is usually carried out at −78 to 100 ° C., preferably 0 to 80 ° C. for 10 minutes to 24 hours.
［製造法２］
一般式［４ａ］の化合物として、たとえば、ジヒドロキシフェニルボロン酸、ピリジン−３−ボロン酸、チオフェン−２−ボロン酸、ベンゾフラン−２−ボロン酸および３−メトキシフェニルボロン酸などが知られている。
一般式［４ｂ］の化合物として、たとえば、３−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）フランなどが知られている。また、一般式［４ａ］および［４ｂ］の化合物は、たとえば、特開２００３−２０６２９０号公報およびザ・ジャーナル・オブ・オーガニック・ケミストリー（The Journal of Organic Chemistry）、1995年、第60巻、p.7508-7510などに記載された方法に準じ、対応するハロゲノ体から製造することができる。As compounds of the general formula [4a], for example, dihydroxyphenylboronic acid, pyridine-3-boronic acid, thiophene-2-boronic acid, benzofuran-2-boronic acid, 3-methoxyphenylboronic acid and the like are known.
As the compound of the general formula [4b], for example, 3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) furan and the like are known. The compounds of the general formulas [4a] and [4b] are, for example, disclosed in JP 2003-206290 A and The Journal of Organic Chemistry, 1995, Vol. 60, p. According to the method described in .7508-7510 etc., it can manufacture from a corresponding halogeno body.
一般式［１ａ］の化合物は、塩基の存在下または不存在下、パラジウム触媒の存在下、リガンドの存在下または不存在下、一般式［３］の化合物を一般式［４ａ］または［４ｂ］の化合物と反応させることにより製造することができる。
この反応で使用される溶媒としては、反応に悪影響を及ぼさないものであれば特に限定されないが、たとえば、水；メタノール、エタノール、２−プロパノールおよび２−メチル−２−プロパノールなどのアルコール類；ベンゼン、トルエンおよびキシレンなどの芳香族炭化水素類；Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミドおよび１−メチル−２−ピロリドンなどのアミド類；塩化メチレン、クロロホルムおよびジクロロエタンなどのハロゲン化炭化水素類；ジオキサン、テトラヒドロフラン、アニソール、エチレングリコールジメチルエーテル、ジエチレングリコールジメチルエーテルおよびジエチレングリコールジエチルエーテルなどのエーテル類；アセトンおよび２−ブタノンなどのケトン類；アセトニトリルなどのニトリル類；酢酸エチルおよび酢酸ブチルなどのエステル類ならびにジメチルスルホキシドなどのスルホキシド類などが挙げられ、これらは混合して使用してもよい。The compound of the general formula [1a] is obtained by converting the compound of the general formula [3] into the general formula [4a] or [4b] in the presence or absence of a base, in the presence of a palladium catalyst, in the presence or absence of a ligand. It can manufacture by making it react with the compound of.
The solvent used in this reaction is not particularly limited as long as it does not adversely influence the reaction. For example, water; alcohols such as methanol, ethanol, 2-propanol and 2-methyl-2-propanol; benzene , Aromatic hydrocarbons such as toluene and xylene; amides such as N, N-dimethylformamide, N, N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane Ethers such as dioxane, tetrahydrofuran, anisole, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and diethylene glycol diethyl ether; ketones such as acetone and 2-butanone; acetonitrile What nitriles; and esters and sulfoxides such as dimethyl sulfoxide, such as ethyl acetate and butyl acetate and the like, may be used which are mixed.
この反応において所望により用いられる塩基としては、たとえば、炭酸水素ナトリウム、炭酸ナトリウム、炭酸カリウム、炭酸セシウムおよびリン酸三カリウムなどの無機塩基ならびにピリジン、４−（ジメチルアミノ）ピリジン、トリエチルアミンおよびジイソプロピルエチルアミンなどの有機塩基が挙げられる。塩基の使用量は、一般式［３］の化合物に対して1〜50倍モル、好ましくは、2〜5倍モルであればよい。
この反応に用いられるパラジウム触媒としては、たとえば、パラジウム−炭素およびパラジウム黒などの金属パラジウム；塩化パラジウムなどの無機パラジウム塩；酢酸パラジウムなどの有機パラジウム塩；テトラキス（トリフェニルホスフィン）パラジウム（０）、ビス（トリフェニルホスフィン）パラジウム（II）クロリド、１，１’−ビス（ジフェニルホスフィノ）フェロセンパラジウム（II）クロリドおよびトリス（ジベンジリデンアセトン）ジパラジウム（０）などの有機パラジウム錯体ならびにポリマー担持ビス（アセタート）トリフェニルホスフィンパラジウム（II）およびポリマー担持ジ（アセタート）ジシクロヘキシルフェニルホスフィンパラジウム（II）などのポリマー固定化有機パラジウム錯体などが挙げられ、これらは組み合わせて使用してもよい。パラジウム触媒の使用量は、一般式［３］の化合物に対して、0.00001〜1倍モル、好ましくは、0.001〜0.1倍モルであればよい。Examples of the base optionally used in this reaction include inorganic bases such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate, cesium carbonate and tripotassium phosphate, and pyridine, 4- (dimethylamino) pyridine, triethylamine and diisopropylethylamine. Of the organic base. The amount of the base used may be 1 to 50 times mol, preferably 2 to 5 times mol, of the compound of the general formula [3].
Examples of the palladium catalyst used in this reaction include metal palladium such as palladium-carbon and palladium black; inorganic palladium salt such as palladium chloride; organic palladium salt such as palladium acetate; tetrakis (triphenylphosphine) palladium (0), Organic palladium complexes such as bis (triphenylphosphine) palladium (II) chloride, 1,1′-bis (diphenylphosphino) ferrocenepalladium (II) chloride and tris (dibenzylideneacetone) dipalladium (0), and polymer-supported bis Examples include polymer-fixed organic palladium complexes such as (acetate) triphenylphosphine palladium (II) and polymer-supported di (acetate) dicyclohexylphenylphosphine palladium (II). It may be used in conjunction look. The usage-amount of a palladium catalyst is 0.00001-1 times mole with respect to the compound of General formula [3], Preferably, what is necessary is just 0.001-0.1 times mole.
この反応において所望により用いられるリガンドとしては、トリメチルホスフィンおよびトリ−ｔｅｒｔ−ブチルホスフィンなどのトリアルキルホスフィン類；トリシクロヘキシルホスフィンなどのトリシクロアルキルホスフィン類；トリフェニルホスフィンおよびトリトリルホスフィンなどのトリアリールホスフィン類；トリメチルホスファイト、トリエチルホスファイトおよびトリブチルホスファイトなどのトリアルキルホスファイト類；トリシクロヘキシルホスファイトなどのトリシクロアルキルホスファイト類；トリフェニルホスファイトなどのトリアリールホスファイト類；１，３−ビス（２，４，６−トリメチルフェニル）イミダゾリウムクロリドなどのイミダゾリウム塩；アセチルアセトンおよびオクタフルオロアセチルアセトンなどのジケトン類；トリメチルアミン、トリエチルアミン、トリプロピルアミンおよびトリイソプロピルアミンなどのアミン類；１，１’−ビス（ジフェニルホスフィノ）フェロセン、２，２’−ビス（ジフェニルホスフィノ）−１，１’−ビナフチル、２−ジシクロヘキシルホスフィノ−２’，６’−ジメトキシビフェニル、２−ジシクロヘキシルホスフィノ−２’，４’，６’−トリイソプロピルビフェニル、２−（ジ−ｔｅｒｔ−ブチルホスフィノ）−２’，４’，６’−トリイソプロピルビフェニルならびに２−（ジ−ｔｅｒｔ−ブチルホスフィノ）ビフェニルなどが挙げられ、これらは組み合わせて使用してもよい。リガンドの使用量は、一般式［３］の化合物に対して0.00001〜1倍モル、好ましくは、0.001〜0.1倍モルであればよい。 The ligands optionally used in this reaction include: trialkylphosphines such as trimethylphosphine and tri-tert-butylphosphine; tricycloalkylphosphines such as tricyclohexylphosphine; triarylphosphine such as triphenylphosphine and tritolylphosphine Trialkyl phosphites such as trimethyl phosphite, triethyl phosphite and tributyl phosphite; tricycloalkyl phosphites such as tricyclohexyl phosphite; triaryl phosphites such as triphenyl phosphite; Imidazolium salts such as bis (2,4,6-trimethylphenyl) imidazolium chloride; acetylacetone and octafluoroacetylacetate Diketones such as trimethylamine, triethylamine, tripropylamine and triisopropylamine; 1,1′-bis (diphenylphosphino) ferrocene, 2,2′-bis (diphenylphosphino) -1,1 '-Binaphthyl, 2-dicyclohexylphosphino-2', 6'-dimethoxybiphenyl, 2-dicyclohexylphosphino-2 ', 4', 6'-triisopropylbiphenyl, 2- (di-tert-butylphosphino)- Examples thereof include 2 ′, 4 ′, 6′-triisopropylbiphenyl and 2- (di-tert-butylphosphino) biphenyl, and these may be used in combination. The amount of the ligand used may be 0.00001 to 1 times mol, preferably 0.001 to 0.1 times mol, of the compound of the general formula [3].
一般式［４ａ］または［４ｂ］の化合物の使用量は、一般式［３］の化合物に対して、1〜50倍モル、好ましくは、1〜2倍モルであればよい。
この反応は、好ましくは、不活性気体（たとえば、窒素、アルゴン）雰囲気下、40〜170℃で1分間〜96時間実施すればよい。The amount of the compound of general formula [4a] or [4b] used may be 1 to 50 times mol, preferably 1 to 2 times mol, of the compound of general formula [3].
This reaction is preferably carried out at 40 to 170 ° C. for 1 minute to 96 hours in an inert gas (eg, nitrogen, argon) atmosphere.
［製造法３］
一般式［５］の化合物として、たとえば、２−（トリブチルスズ）チアゾールおよび２−（トリブチルスズ）フランなどが知られている。
一般式［１ｂ］の化合物は、酸化銀の存在下または不存在下、パラジウム触媒の存在下、一般式［３］の化合物を一般式［５］の化合物と反応させることにより製造することができる。
この反応で使用される溶媒としては、反応に悪影響を及ぼさないものであれば特に限定されないが、たとえば、ベンゼン、トルエンおよびキシレンなどの芳香族炭化水素類；Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミドおよび１−メチル−２−ピロリドンなどのアミド類；ジオキサン、テトラヒドロフラン、アニソール、エチレングリコールジメチルエーテル、ジエチレングリコールジメチルエーテルおよびジエチレングリコールジエチルエーテルなどのエーテル類；アセトニトリルなどのニトリル類ならびにジメチルスルホキシドなどのスルホキシド類などが挙げられ、これらは混合して使用してもよい。As the compound of the general formula [5], for example, 2- (tributyltin) thiazole and 2- (tributyltin) furan are known.
The compound of the general formula [1b] can be produced by reacting the compound of the general formula [3] with the compound of the general formula [5] in the presence or absence of silver oxide and in the presence of a palladium catalyst. .
The solvent used in this reaction is not particularly limited as long as it does not adversely influence the reaction. For example, aromatic hydrocarbons such as benzene, toluene and xylene; N, N-dimethylformamide, N, N Amides such as dimethylacetamide and 1-methyl-2-pyrrolidone; Ethers such as dioxane, tetrahydrofuran, anisole, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and diethylene glycol diethyl ether; Nitriles such as acetonitrile and sulfoxides such as dimethyl sulfoxide, etc. These may be used as a mixture.
この反応に用いられるパラジウム触媒としては、たとえば、テトラキス（トリフェニルホスフィン）パラジウム（０）、ビス（トリフェニルホスフィン）パラジウム（II）クロリド、１，１’−ビス（ジフェニルホスフィノ）フェロセンパラジウム（II）クロリドおよびトリス（ジベンジリデンアセトン）ジパラジウム（０）などの有機パラジウム錯体ならびにポリマー担持ビス（アセタート）トリフェニルホスフィンパラジウム（II）およびポリマー担持ジ（アセタート）ジシクロヘキシルフェニルホスフィンパラジウム（II）などのポリマー固定化有機パラジウム錯体などが挙げられ、これらは組み合わせて使用してもよい。パラジウム触媒の使用量は、一般式［３］の化合物に対して、0.00001〜1倍モル、好ましくは、0.001〜0.1倍モルであればよい。
この反応において所望により用いられる酸化銀の使用量は、一般式［３］の化合物に対して、1〜50倍モル、好ましくは、1〜10倍モルであればよい。
一般式［５］の化合物の使用量は、一般式［３］の化合物に対して、1〜50倍モル、好ましくは、1〜2倍モルであればよい。
この反応は、好ましくは、不活性気体（たとえば、窒素、アルゴン）雰囲気下、40〜170℃で1分間〜96時間実施すればよい。Examples of the palladium catalyst used in this reaction include tetrakis (triphenylphosphine) palladium (0), bis (triphenylphosphine) palladium (II) chloride, 1,1′-bis (diphenylphosphino) ferrocene palladium (II ) Organic palladium complexes such as chloride and tris (dibenzylideneacetone) dipalladium (0) and polymers such as polymer supported bis (acetate) triphenylphosphine palladium (II) and polymer supported di (acetate) dicyclohexylphenylphosphine palladium (II) Examples thereof include an immobilized organic palladium complex, and these may be used in combination. The usage-amount of a palladium catalyst is 0.00001-1 times mole with respect to the compound of General formula [3], Preferably, what is necessary is just 0.001-0.1 times mole.
The amount of silver oxide used as desired in this reaction may be 1 to 50 times mol, preferably 1 to 10 times mol, of the compound of general formula [3].
The amount of the compound of general formula [5] used may be 1 to 50 times mol, preferably 1 to 2 times mol, of the compound of general formula [3].
This reaction is preferably carried out at 40 to 170 ° C. for 1 minute to 96 hours in an inert gas (eg, nitrogen, argon) atmosphere.
［製造法４］
一般式［６］の化合物として、たとえば、ピロリジン、ピペリジン、モルホリン、ピロール、インドリン、イソインドリン、ベンズイミダゾールおよびインドールなどが知られている。 As the compound of the general formula [6], for example, pyrrolidine, piperidine, morpholine, pyrrole, indoline, isoindoline, benzimidazole and indole are known.
一般式［１ｃ］の化合物は、製造法２に準じて、一般式［３］の化合物を一般式［６］の化合物と反応させることにより製造することができる。 The compound of the general formula [1c] can be produced by reacting the compound of the general formula [3] with the compound of the general formula [6] according to the production method 2.
［製造法５］
一般式［７］の化合物として、たとえば、シクロペンテンおよびシクロヘキセンなどが知られている。また、一般式［７］の化合物は、たとえば、実験化学講座、1992年、第4版、第19巻、p.53-298、丸善に記載の方法またはそれに準じた方法で製造することができる。 As compounds of the general formula [7], for example, cyclopentene and cyclohexene are known. The compound of the general formula [7] can be produced, for example, by the method described in Experimental Chemistry Course, 1992, 4th edition, volume 19, p.53-298, Maruzen or a method analogous thereto. .
（５−１）
一般式［１ｄ］の化合物は、塩基の存在下または不存在下、相関移動触媒の存在下または不存在下、リガンドの存在下または不存在下、パラジウム触媒の存在下、一般式［３］の化合物を一般式［７］の化合物と反応させることにより製造することができる。
この反応で使用される溶媒としては、反応に悪影響を及ぼさないものであれば特に限定されないが、たとえば、水；メタノール、エタノール、２−プロパノールおよび２−メチル−２−プロパノールなどのアルコール類；ベンゼン、トルエンおよびキシレンなどの芳香族炭化水素類；Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミドおよび１−メチル−２−ピロリドンなどのアミド類；塩化メチレン、クロロホルムおよびジクロロエタンなどのハロゲン化炭化水素類；ジオキサン、テトラヒドロフラン、アニソール、エチレングリコールジメチルエーテル、ジエチレングリコールジメチルエーテルおよびジエチレングリコールジエチルエーテルなどのエーテル類；アセトンおよび２−ブタノンなどのケトン類；アセトニトリルなどのニトリル類；酢酸エチルおよび酢酸ブチルなどのエステル類ならびにジメチルスルホキシドなどのスルホキシド類などが挙げられ、これらは混合して使用してもよい。
この反応において所望により用いられる塩基としては、たとえば、水素化ナトリウム、炭酸水素ナトリウム、炭酸ナトリウム、炭酸カリウム、炭酸セシウムおよびリン酸三カリウムなどの無機塩基ならびに酢酸ナトリウム、酢酸カリウム、ナトリウム＝ｔｅｒｔ−ブトキシド、トリエチルアミン、ジイソプロピルエチルアミン、トリブチルアミンおよびＮ，Ｎ−ジシクロヘキシルメチルアミンなどの有機塩基が挙げられる。塩基の使用量は、一般式［３］の化合物に対して1〜50倍モル、好ましくは、2〜5倍モルであればよい。(5-1)
The compound of the general formula [1d] is represented by the general formula [3] in the presence or absence of a base, in the presence or absence of a phase transfer catalyst, in the presence or absence of a ligand, in the presence of a palladium catalyst. It can be produced by reacting the compound with a compound of the general formula [7].
The solvent used in this reaction is not particularly limited as long as it does not adversely influence the reaction. For example, water; alcohols such as methanol, ethanol, 2-propanol and 2-methyl-2-propanol; benzene , Aromatic hydrocarbons such as toluene and xylene; amides such as N, N-dimethylformamide, N, N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane Ethers such as dioxane, tetrahydrofuran, anisole, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and diethylene glycol diethyl ether; ketones such as acetone and 2-butanone; acetonitrile What nitriles; and esters and sulfoxides such as dimethyl sulfoxide, such as ethyl acetate and butyl acetate and the like, may be used which are mixed.
Bases optionally used in this reaction include, for example, inorganic bases such as sodium hydride, sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate and tripotassium phosphate, and sodium acetate, potassium acetate, sodium = tert-butoxide. And organic bases such as triethylamine, diisopropylethylamine, tributylamine and N, N-dicyclohexylmethylamine. The amount of the base used may be 1 to 50 times mol, preferably 2 to 5 times mol, of the compound of the general formula [3].
この反応において所望により用いられる相間移動触媒としては、たとえば、テトラメチルアンモニウムクロリド、ベンジルトリメチルアンモニウムクロリド、ベンジルトリエチルアンモニウムクロリド、ベンジルトリブチルアンモニウムクロリド、テトラブチルアンモニウムクロリド、テトラブチルアンモニウムブロミド、テトラブチルアンモニウムハイドロゲンサルフェートおよびトリオクチルメチルアンモニウムクロリドなどの４級アンモニウム塩；Ｎ−ラウリルピリジニウムクロリド、Ｎ−ラウリル−４−ピコリニウムクロリド、Ｎ−ラウリルピコリニウムクロリドならびにＮ−ベンジルピコリニウムクロリドなどが挙げられる。相間移動触媒の使用量は、一般式［３］の化合物に対して0.01〜50倍モル、好ましくは、0.1〜5倍モルであればよい。 Examples of the phase transfer catalyst optionally used in this reaction include tetramethylammonium chloride, benzyltrimethylammonium chloride, benzyltriethylammonium chloride, benzyltributylammonium chloride, tetrabutylammonium chloride, tetrabutylammonium bromide, and tetrabutylammonium hydrogen sulfate. And quaternary ammonium salts such as trioctylmethylammonium chloride; N-laurylpyridinium chloride, N-lauryl-4-picolinium chloride, N-laurylpicolinium chloride, N-benzylpicolinium chloride and the like. The amount of the phase transfer catalyst used may be 0.01 to 50 times mol, preferably 0.1 to 5 times mol for the compound of general formula [3].
この反応において所望により用いられるリガンドとしては、トリメチルホスフィンおよびトリ−ｔｅｒｔ−ブチルホスフィンなどのトリアルキルホスフィン類；トリシクロヘキシルホスフィンなどのトリシクロアルキルホスフィン類；トリフェニルホスフィンおよびトリトリルホスフィンなどのトリアリールホスフィン類；トリメチルホスファイト、トリエチルホスファイトおよびトリブチルホスファイトなどのトリアルキルホスファイト類；トリシクロヘキシルホスファイトなどのトリシクロアルキルホスファイト類；トリフェニルホスファイトなどのトリアリールホスファイト類；１，３−ビス（２，４，６−トリメチルフェニル）イミダゾリウムクロリドなどのイミダゾリウム塩；アセチルアセトンおよびオクタフルオロアセチルアセトンなどのジケトン類；トリメチルアミン、トリエチルアミン、トリプロピルアミンおよびトリイソプロピルアミンなどのアミン類；１，１’−ビス（ジフェニルホスフィノ）フェロセン、２，２’−ビス（ジフェニルホスフィノ）−１，１’−ビナフチル、２−ジシクロヘキシルホスフィノ−２’，６’−ジメトキシビフェニル、２−ジシクロヘキシルホスフィノ−２’，４’，６’−トリイソプロピルビフェニル、２−（ジ−ｔｅｒｔ−ブチルホスフィノ）−２’，４’，６’−トリイソプロピルビフェニルならびに２−（ジ−ｔｅｒｔ−ブチルホスフィノ）ビフェニルなどが挙げられ、これらは組み合わせて使用してもよい。リガンドの使用量は、一般式［３］の化合物に対して0.00001〜1倍モル、好ましくは、0.001〜0.1倍モルであればよい。 The ligands optionally used in this reaction include: trialkylphosphines such as trimethylphosphine and tri-tert-butylphosphine; tricycloalkylphosphines such as tricyclohexylphosphine; triarylphosphine such as triphenylphosphine and tritolylphosphine Trialkyl phosphites such as trimethyl phosphite, triethyl phosphite and tributyl phosphite; tricycloalkyl phosphites such as tricyclohexyl phosphite; triaryl phosphites such as triphenyl phosphite; Imidazolium salts such as bis (2,4,6-trimethylphenyl) imidazolium chloride; acetylacetone and octafluoroacetylacetate Diketones such as trimethylamine, triethylamine, tripropylamine and triisopropylamine; 1,1′-bis (diphenylphosphino) ferrocene, 2,2′-bis (diphenylphosphino) -1,1 '-Binaphthyl, 2-dicyclohexylphosphino-2', 6'-dimethoxybiphenyl, 2-dicyclohexylphosphino-2 ', 4', 6'-triisopropylbiphenyl, 2- (di-tert-butylphosphino)- Examples thereof include 2 ′, 4 ′, 6′-triisopropylbiphenyl and 2- (di-tert-butylphosphino) biphenyl, and these may be used in combination. The amount of the ligand used may be 0.00001 to 1 times mol, preferably 0.001 to 0.1 times mol, of the compound of the general formula [3].
この反応に用いられるパラジウム触媒としては、たとえば、パラジウム−炭素およびパラジウム黒などの金属パラジウム；塩化パラジウムなどの無機パラジウム塩；酢酸パラジウムなどの有機パラジウム塩；テトラキス（トリフェニルホスフィン）パラジウム（０）、ビス（トリフェニルホスフィン）パラジウム（II）クロリド、１，１’−ビス（ジフェニルホスフィノ）フェロセンパラジウム（II）クロリド、（Ｅ）−ジ（μ−アセタート）ビス（ｏ−（ジ−ｏ−トリルホスフィノ）ベンジル）ジパラジウム（II）およびトリス（ジベンジリデンアセトン）ジパラジウム（０）などの有機パラジウム錯体ならびにポリマー担持ビス（アセタート）トリフェニルホスフィンパラジウム（II）およびポリマー担持ジ（アセタート）ジシクロヘキシルフェニルホスフィンパラジウム（II）などのポリマー固定化有機パラジウム錯体などが挙げられ、これらは組み合わせて使用してもよい。パラジウム触媒の使用量は、一般式［３］の化合物に対して、0.00001〜1倍モル、好ましくは、0.001〜0.1倍モルであればよい。 Examples of the palladium catalyst used in this reaction include metal palladium such as palladium-carbon and palladium black; inorganic palladium salt such as palladium chloride; organic palladium salt such as palladium acetate; tetrakis (triphenylphosphine) palladium (0), Bis (triphenylphosphine) palladium (II) chloride, 1,1′-bis (diphenylphosphino) ferrocenepalladium (II) chloride, (E) -di (μ-acetate) bis (o- (di-o-tolylphosphino) ) Benzyl) dipalladium (II) and tris (dibenzylideneacetone) dipalladium (0) and other organopalladium complexes and polymer-supported bis (acetate) triphenylphosphine palladium (II) and polymer-supported di (acetate) dicyclohexyl Examples include polymer-fixed organic palladium complexes such as phenylphosphine palladium (II), and these may be used in combination. The usage-amount of a palladium catalyst is 0.00001-1 times mole with respect to the compound of General formula [3], Preferably, what is necessary is just 0.001-0.1 times mole.
一般式［７］の化合物の使用量は、一般式［３］の化合物に対して、1〜50倍モル、好ましくは、1〜2倍モルであればよい。
この反応は、好ましくは、不活性気体（たとえば、窒素、アルゴン）雰囲気下、40〜170℃で1分間〜24時間実施すればよい。The amount of the compound of general formula [7] used may be 1 to 50 times mol, preferably 1 to 2 times mol, of the compound of general formula [3].
This reaction is preferably carried out at 40 to 170 ° C. for 1 minute to 24 hours in an inert gas (for example, nitrogen, argon) atmosphere.
（５−２）
一般式［１ｅ］の化合物は、一般式［１ｄ］の化合物を還元することにより製造できる。
還元反応としては、たとえば、金属触媒を用いる接触水素添加反応が挙げられる。
この反応で使用される溶媒としては、反応に悪影響を及ぼさないものであれば特に限定されないが、たとえば、水；メタノール、エタノール、２−プロパノールおよび２−メチル−２−プロパノールなどのアルコール類；Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミドおよび１−メチル−２−ピロリドンなどのアミド類；塩化メチレン、クロロホルムおよびジクロロエタンなどのハロゲン化炭化水素類；ベンゼン、トルエンおよびキシレンなどの芳香族炭化水素類；ジオキサン、テトラヒドロフラン、アニソール、エチレングリコールジメチルエーテル、ジエチレングリコールジメチルエーテルおよびジエチレングリコールジエチルエーテルなどのエーテル類；アセトニトリルなどのニトリル類；アセトンおよび２−ブタノンなどのケトン類；酢酸エチルおよび酢酸ブチルなどのエステル類；酢酸などのカルボン酸類ならびにピリジンなどのヘテロ芳香族類などが挙げられ、これらは混合して使用してもよい。
この反応に使用される金属触媒としては、たとえば、パラジウム−炭素およびパラジウム黒などの金属パラジウム；酸化パラジウムおよび水酸化パラジウムなどのパラジウム塩；ラネーニッケルなどのニッケル金属ならびに酸化白金などの白金塩などが挙げられる。金属触媒の使用量は、一般式［１ｄ］の化合物に対して0.001〜5倍量（Ｗ/Ｗ）、好ましくは、0.01〜1倍量（Ｗ/Ｗ）であればよい。
水素源としては、たとえば、水素；ギ酸；ギ酸ナトリウム、ギ酸アンモニウムおよびギ酸トリエチルアンモニウムなどのギ酸塩；シクロヘキセンならびにシクロヘキサジエンなどが挙げられる。水素源の使用量は、一般式［１ｄ］の化合物に対して2〜100倍モル、好ましくは、2〜10倍モルであればよい。
この反応は、0〜200℃、好ましくは、0〜100℃で1分間〜24時間実施すればよい。(5-2)
The compound of the general formula [1e] can be produced by reducing the compound of the general formula [1d].
Examples of the reduction reaction include a catalytic hydrogenation reaction using a metal catalyst.
The solvent used in this reaction is not particularly limited as long as it does not adversely influence the reaction. For example, water; alcohols such as methanol, ethanol, 2-propanol and 2-methyl-2-propanol; N Amides such as N, N-dimethylformamide, N, N-dimethylacetamide and 1-methyl-2-pyrrolidone; Halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; Aromatic hydrocarbons such as benzene, toluene and xylene Ethers such as dioxane, tetrahydrofuran, anisole, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and diethylene glycol diethyl ether; nitriles such as acetonitrile; acetone and 2-butano Ketones such as, esters such as ethyl acetate and butyl acetate; and heteroaromatics such as carboxylic acids and pyridine such as acetic, and the like, may be used which are mixed.
Examples of the metal catalyst used in this reaction include palladium metal such as palladium-carbon and palladium black; palladium salts such as palladium oxide and palladium hydroxide; nickel metals such as Raney nickel and platinum salts such as platinum oxide. It is done. The amount of the metal catalyst used may be 0.001 to 5 times (W / W), preferably 0.01 to 1 times (W / W) of the compound of the general formula [1d].
Examples of the hydrogen source include hydrogen; formic acid; formate salts such as sodium formate, ammonium formate and triethylammonium formate; cyclohexene and cyclohexadiene. The usage-amount of a hydrogen source should just be 2-100 times mole with respect to the compound of general formula [1d], Preferably, it may be 2-10 times mole.
This reaction may be carried out at 0 to 200 ° C., preferably 0 to 100 ° C. for 1 minute to 24 hours.
［製造法６］
一般式［１］の化合物は、塩基の存在下または不存在下、一般式［８］の化合物を酸ハロゲン化物または酸無水物と反応させることにより製造することができる。
この反応で使用される溶媒としては、反応に悪影響を及ぼさないものであれば特に限定されないが、たとえば、Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミドおよび１−メチル−２−ピロリドンなどのアミド類；塩化メチレン、クロロホルムおよびジクロロエタンなどのハロゲン化炭化水素類；ベンゼン、トルエンおよびキシレンなどの芳香族炭化水素類；ジオキサン、テトラヒドロフラン、アニソール、エチレングリコールジメチルエーテル、ジエチレングリコールジメチルエーテルおよびジエチレングリコールジエチルエーテルなどのエーテル類；アセトニトリルなどのニトリル類；アセトンおよび２−ブタノンなどのケトン類；酢酸エチルおよび酢酸ブチルなどのエステル類；スルホランなどのスルホン類ならびにジメチルスルホキシドなどのスルホキシド類などが挙げられ、これらは混合して使用してもよい。The compound of general formula [1] can be produced by reacting the compound of general formula [8] with an acid halide or acid anhydride in the presence or absence of a base.
The solvent used in this reaction is not particularly limited as long as it does not adversely affect the reaction, and examples thereof include N, N-dimethylformamide, N, N-dimethylacetamide and 1-methyl-2-pyrrolidone. Amides; Halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; Aromatic hydrocarbons such as benzene, toluene and xylene; Ethers such as dioxane, tetrahydrofuran, anisole, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and diethylene glycol diethyl ether Nitriles such as acetonitrile; ketones such as acetone and 2-butanone; esters such as ethyl acetate and butyl acetate; sulfones such as sulfolane; Sulfoxide is like sulfoxides such as may be used in these mixed.
この反応に用いられる酸ハロゲン化物としては、たとえば、ベンゾイルクロリド、ベンゾイルブロミド、２，４−ジフルオロベンゾイルクロリド、２−ナフトイルクロリド、ジフェニルアセチルクロリド、２，３−ジヒドロベンゾ［１，４］ジオキシン−６−カルボニルクロリド、シクロヘキサンカルボニルクロリド、シクロペンチルカルボニルクロリド、（Ｅ）−３−フェニルアクリロイルクロリド、フェノキシアセチルクロリド、２−フロイルクロリド、１−ベンゾフラン−２−カルボニルクロリド、２−テノイルクロリド、ニコチノイルクロリドおよびピコリノイルクロリドなどが挙げられる。また、酸ハロゲン化物は、一般式［９］
酸ハロゲン化物の使用量は、一般式［８］の化合物に対して、1〜50倍モル、好ましくは、１〜5倍モルであればよい。
この反応に用いられる酸無水物としては、たとえば、無水フタル酸および無水安息香酸などが挙げられる。また、酸無水物は、対応するカルボン酸から、たとえば、新実験化学講座、1977年、第14巻、p.1120-1133、丸善に記載の方法またはそれに準じた方法で製造することができる。酸無水物の使用量は、一般式［８］の化合物に対して、1〜50倍モル、好ましくは、１〜5倍モルであればよい。
この反応において所望により用いられる塩基としては、たとえば、炭酸水素ナトリウム、炭酸ナトリウム、炭酸カリウムおよび炭酸セシウムなどの無機塩基ならびにトリエチルアミンおよびジイソプロピルエチルアミンなどの有機塩基が挙げられる。塩基の使用量は、一般式［８］の化合物に対して1〜50倍モル、好ましくは、1〜5倍モルであればよい。
この反応は、通常、−78〜100℃、好ましくは、0〜80℃で10分間〜24時間実施すればよい。Examples of the acid halide used in this reaction include benzoyl chloride, benzoyl bromide, 2,4-difluorobenzoyl chloride, 2-naphthoyl chloride, diphenylacetyl chloride, 2,3-dihydrobenzo [1,4] dioxin- 6-carbonyl chloride, cyclohexanecarbonyl chloride, cyclopentylcarbonyl chloride, (E) -3-phenylacryloyl chloride, phenoxyacetyl chloride, 2-furoyl chloride, 1-benzofuran-2-carbonyl chloride, 2-thenoyl chloride, nicotinoyl Examples include chloride and picolinoyl chloride. The acid halide has the general formula [9].
The amount of the acid halide to be used may be 1 to 50 times mol, preferably 1 to 5 times mol, of the compound of the general formula [8].
Examples of the acid anhydride used in this reaction include phthalic anhydride and benzoic anhydride. An acid anhydride can be produced from the corresponding carboxylic acid by, for example, the method described in Shin-ken Kagaku Koza, 1977, Vol. 14, p.1120-1133, Maruzen or a method analogous thereto. The usage-amount of an acid anhydride is 1-50 times mole with respect to the compound of General formula [8], Preferably, what is necessary is just 1-5 times mole.
Examples of the base optionally used in this reaction include inorganic bases such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate and cesium carbonate, and organic bases such as triethylamine and diisopropylethylamine. The amount of the base used may be 1 to 50 times mol, preferably 1 to 5 times mol, of the compound of the general formula [8].
This reaction is usually carried out at −78 to 100 ° C., preferably 0 to 80 ° C. for 10 minutes to 24 hours.
［製造法７］
一般式［１ｇ］の化合物は、塩基の存在下または不存在下、相関移動触媒の存在下または不存在下、一般式［１ｆ］の化合物をハロゲン化アルキルまたは硫酸アルキルエステルと反応させることにより製造することができる。
この反応で使用される溶媒としては、反応に悪影響を及ぼさないものであれば特に限定されないが、たとえば、Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミドおよび１−メチル−２−ピロリドンなどのアミド類；塩化メチレン、クロロホルムおよびジクロロエタンなどのハロゲン化炭化水素類；ベンゼン、トルエンおよびキシレンなどの芳香族炭化水素類；ジオキサン、テトラヒドロフラン、アニソール、エチレングリコールジメチルエーテル、ジエチレングリコールジメチルエーテルおよびジエチレングリコールジエチルエーテルなどのエーテル類；アセトニトリルなどのニトリル類；アセトンおよび２−ブタノンなどのケトン類；酢酸エチルおよび酢酸ブチルなどのエステル類；スルホランなどのスルホン類ならびにジメチルスルホキシドなどのスルホキシド類などが挙げられ、これらは混合して使用してもよい。The compound of the general formula [1g] is produced by reacting the compound of the general formula [1f] with an alkyl halide or an alkyl sulfate in the presence or absence of a base and in the presence or absence of a phase transfer catalyst. can do.
The solvent used in this reaction is not particularly limited as long as it does not adversely affect the reaction, and examples thereof include N, N-dimethylformamide, N, N-dimethylacetamide and 1-methyl-2-pyrrolidone. Amides; Halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; Aromatic hydrocarbons such as benzene, toluene and xylene; Ethers such as dioxane, tetrahydrofuran, anisole, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and diethylene glycol diethyl ether Nitriles such as acetonitrile; ketones such as acetone and 2-butanone; esters such as ethyl acetate and butyl acetate; sulfones such as sulfolane; Sulfoxide is like sulfoxides such as may be used in these mixed.
この反応に用いられるハロゲン化アルキルとしては、たとえば、ヨウ化メチル、ヨウ化エチル、ブチルブロミド、アリルブロミドおよびアリルクロリドなどが挙げられる。ハロゲン化アルキルの使用量は、一般式［１ｆ］の化合物に対して、1〜50倍モル、好ましくは、１〜2倍モルであればよい。
この反応に用いられる硫酸アルキルエステルとしては、たとえば、硫酸ジメチルまたは硫酸ジエチルなどが挙げられる。硫酸アルキルエステルの使用量は、一般式［１ｆ］の化合物に対して、1〜50倍モル、好ましくは、１〜2倍モルであればよい。Examples of the alkyl halide used in this reaction include methyl iodide, ethyl iodide, butyl bromide, allyl bromide, and allyl chloride. The amount of the alkyl halide to be used may be 1 to 50 times mol, preferably 1 to 2 times mol, of the compound of the general formula [1f].
Examples of the alkyl sulfate used in this reaction include dimethyl sulfate and diethyl sulfate. The usage-amount of a sulfuric-acid alkylester should just be 1-50 times mole with respect to the compound of general formula [1f], Preferably, it may be 1-2 times mole.
この反応において所望により用いられる塩基としては、たとえば、水酸化ナトリウム、水酸化カリウム、炭酸水素ナトリウム、炭酸ナトリウム、炭酸カリウム、炭酸セシウムおよびリン酸三カリウムなどの無機塩基ならびに酢酸ナトリウム、酢酸カリウム、トリエチルアミン、ジイソプロピルエチルアミン、トリブチルアミンおよびＮ，Ｎ−ジシクロヘキシルメチルアミンなどの有機塩基が挙げられる。塩基の使用量は、一般式［１ｆ］の化合物に対して1〜1000倍モル、好ましくは、2〜100倍モルであればよい。 Bases optionally used in this reaction include, for example, sodium hydroxide, potassium hydroxide, sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate and tripotassium phosphate, and sodium acetate, potassium acetate, triethylamine. And organic bases such as diisopropylethylamine, tributylamine and N, N-dicyclohexylmethylamine. The amount of the base used may be 1 to 1000 times mol, preferably 2 to 100 times mol, of the compound of the general formula [1f].
この反応において所望により用いられる相間移動触媒としては、たとえば、テトラメチルアンモニウムクロリド、ベンジルトリメチルアンモニウムクロリド、ベンジルトリエチルアンモニウムクロリド、ベンジルトリブチルアンモニウムクロリド、テトラブチルアンモニウムクロリド、テトラブチルアンモニウムブロミド、テトラブチルアンモニウムハイドロゲンサルフェートおよびトリオクチルメチルアンモニウムクロリドなどの４級アンモニウム塩；Ｎ−ラウリルピリジニウムクロリド、Ｎ−ラウリル−４−ピコリニウムクロリド、Ｎ−ラウリルピコリニウムクロリドならびにＮ−ベンジルピコリニウムクロリドなどが挙げられる。相間移動触媒の使用量は、一般式［１ｆ］の化合物に対して0.01〜50倍モル、好ましくは、0.1〜5倍モルであればよい。
この反応は、通常、−78〜100℃、好ましくは、0〜80℃で10分間〜24時間実施すればよい。Examples of the phase transfer catalyst optionally used in this reaction include tetramethylammonium chloride, benzyltrimethylammonium chloride, benzyltriethylammonium chloride, benzyltributylammonium chloride, tetrabutylammonium chloride, tetrabutylammonium bromide, and tetrabutylammonium hydrogen sulfate. And quaternary ammonium salts such as trioctylmethylammonium chloride; N-laurylpyridinium chloride, N-lauryl-4-picolinium chloride, N-laurylpicolinium chloride, N-benzylpicolinium chloride and the like. The amount of the phase transfer catalyst used may be 0.01 to 50 times mol, preferably 0.1 to 5 times mol, of the compound of the general formula [1f].
This reaction is usually carried out at −78 to 100 ° C., preferably 0 to 80 ° C. for 10 minutes to 24 hours.
［製造法８］
一般式［１１］の化合物として、たとえば、２−ブロモピリジン、２−ブロモピリミジンおよびクロロピラジンなどが知られている。 As the compound of the general formula [11], for example, 2-bromopyridine, 2-bromopyrimidine, chloropyrazine and the like are known.
一般式［１ａ］の化合物は、製造法２に準じて、一般式［１０］の化合物を一般式［１１］の化合物と反応させることにより製造することができる。 The compound of the general formula [1a] can be produced by reacting the compound of the general formula [10] with the compound of the general formula [11] according to the production method 2.
このようにして得られた一般式［１］、［１ａ］、［１ｂ］、［１ｃ］、［１ｄ］、［１ｅ］、［１ｆ］および［１ｇ］の化合物またはそれらの塩は、たとえば、縮合、付加、酸化、還元、転位、置換、ハロゲン化、脱水もしくは加水分解などの自体公知の反応に付すことによって、またはそれらの反応を適宜組み合わせることによって、他の一般式［１］の化合物またはその塩に誘導することができる。
また、上記した製造法における化合物において、異性体（たとえば、光学異性体、幾何異性体および互変異性体など）が存在する場合、これらの異性体も使用することができ、また、溶媒和物、水和物および種々の形状の結晶も使用することができる。The compounds of the general formulas [1], [1a], [1b], [1c], [1d], [1e], [1f] and [1g] thus obtained or their salts are, for example, By subjecting to a reaction known per se such as condensation, addition, oxidation, reduction, rearrangement, substitution, halogenation, dehydration or hydrolysis, or by appropriately combining these reactions, other compounds of general formula [1] or It can be derived to its salt.
Moreover, in the compound in the above production method, when there are isomers (for example, optical isomers, geometric isomers, tautomers, etc.), these isomers can also be used, and solvates. Hydrates and crystals of various shapes can also be used.
次に、本発明化合物の製造の原料である一般式［２］、［３］、［８］および［１０］の化合物の製造法について説明する。 Next, a method for producing the compounds of the general formulas [2], [3], [8] and [10], which are raw materials for producing the compound of the present invention, will be described.
［製造法Ａ］
一般式［１２ａ］の化合物として、たとえば、４−ブロモ−２−ニトロアニリンおよび４−ブロモ−２−メチル−６−ニトロアニリンなどが知られている。 As compounds of the general formula [12a], for example, 4-bromo-2-nitroaniline and 4-bromo-2-methyl-6-nitroaniline are known.
一般式［１２ｂ］の化合物は、製造法７に準じて、一般式［１２ａ］の化合物をアルキル化することにより製造することができる。 The compound of the general formula [12b] can be produced by alkylating the compound of the general formula [12a] according to the production method 7.
［製造法Ｂ］
一般式［１２］の化合物として、たとえば、４−ブロモ−Ｎ−メチル−２−ニトロアニリンなどが知られている。 As a compound of the general formula [12], for example, 4-bromo-N-methyl-2-nitroaniline and the like are known.
一般式［１３ａ］の化合物は、製造法２に準じて、一般式［１２］の化合物を一般式［４ａ］または一般式［４ｂ］の化合物と反応させることにより製造することができる。 The compound of the general formula [13a] can be produced by reacting the compound of the general formula [12] with the compound of the general formula [4a] or the general formula [4b] according to the production method 2.
［製造法Ｃ］
Ｙ１ａが、置換されていてもよいアルケニレンまたはアルキニレン基である、一般式［１４］の化合物として、たとえば、スチレン、アリルベンゼン、４−フェニル−１−ブテン、ビニルシクロヘキサンおよびアリルシクロヘキサンなどが知られている。また、一般式［１４］の化合物は、たとえば、実験化学講座、1992年、第４版、第19巻、p.298-361、丸善に記載の方法またはそれに準じた方法で製造することができる。As the compound of the general formula [14], wherein Y 1a is an optionally substituted alkenylene or alkynylene group, for example, styrene, allylbenzene, 4-phenyl-1-butene, vinylcyclohexane and allylcyclohexane are known. ing. The compound of the general formula [14] can be produced, for example, by the method described in Experimental Chemistry Course, 1992, 4th edition, volume 19, p.298-361, Maruzen or a method analogous thereto. .
Ｙ１ａが、保護されていてもよいイミノ基である、一般式［１４］の化合物として、たとえば、アニリンまたは２−フルオロアニリンなどが知られている。また、一般式［１４］の化合物は、たとえば、対応するハロゲノ化合物から、常法により製造することができる。As the compound of the general formula [14], wherein Y 1a is an optionally protected imino group, for example, aniline or 2-fluoroaniline is known. Moreover, the compound of General formula [14] can be manufactured by a conventional method from a corresponding halogeno compound, for example.
（Ｃ−１）
Ｙ１ａが、置換されていてもよいアルケニレン基または保護されていてもよいイミノ基の場合、一般式［１３ｂ］の化合物は、製造法（５−１）に準じて、一般式［１２］の化合物を一般式［１４］の化合物と反応させることにより製造することができる。(C-1)
When Y 1a is an optionally substituted alkenylene group or an optionally protected imino group, the compound of the general formula [13b] is represented by the general formula [12] according to the production method (5-1). It can be produced by reacting the compound with a compound of the general formula [14].
（Ｃ−２）
Ｙ１ａが、置換されていてもよいアルキニレン基の場合、一般式［１３ｂ］の化合物は、塩基の存在下または不存在下、銅触媒存在下または不存在下、パラジウム触媒の存在下、一般式［１２］の化合物を一般式［１４］の化合物と反応させることにより製造することができる。
この反応で使用される溶媒としては、反応に悪影響を及ぼさないものであれば特に限定されないが、たとえば、水；メタノール、エタノール、２−プロパノールおよび２−メチル−２−プロパノールなどのアルコール類；ベンゼン、トルエンおよびキシレンなどの芳香族炭化水素類；Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミドおよび１−メチル−２−ピロリドンなどのアミド類；塩化メチレン、クロロホルムおよびジクロロエタンなどのハロゲン化炭化水素類；ジオキサン、テトラヒドロフラン、アニソール、エチレングリコールジメチルエーテル、ジエチレングリコールジメチルエーテルおよびジエチレングリコールジエチルエーテルなどのエーテル類；アセトンおよび２−ブタノンなどのケトン類；アセトニトリルなどのニトリル類；酢酸エチルおよび酢酸ブチルなどのエステル類ならびにジメチルスルホキシドなどのスルホキシド類などが挙げられ、これらは混合して使用してもよい。(C-2)
When Y 1a is an optionally substituted alkynylene group, the compound of the general formula [13b] is represented by the general formula in the presence or absence of a base, in the presence or absence of a copper catalyst, in the presence of a palladium catalyst. It can manufacture by making the compound of [12] react with the compound of general formula [14].
The solvent used in this reaction is not particularly limited as long as it does not adversely influence the reaction. For example, water; alcohols such as methanol, ethanol, 2-propanol and 2-methyl-2-propanol; benzene , Aromatic hydrocarbons such as toluene and xylene; amides such as N, N-dimethylformamide, N, N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane Ethers such as dioxane, tetrahydrofuran, anisole, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and diethylene glycol diethyl ether; ketones such as acetone and 2-butanone; acetonitrile What nitriles; and esters and sulfoxides such as dimethyl sulfoxide, such as ethyl acetate and butyl acetate and the like, may be used which are mixed.
この反応において所望により用いられる塩基としては、たとえば、炭酸水素ナトリウム、炭酸ナトリウム、炭酸カリウム、炭酸セシウムおよびリン酸三カリウムなどの無機塩基ならびにトリエチルアミンおよびジイソプロピルエチルアミンなどの有機塩基が挙げられる。塩基の使用量は、一般式［１２］の化合物に対して1〜50倍モル、好ましくは、2〜5倍モルであればよい。
この反応において所望により用いられる銅触媒としては、たとえば、臭化銅およびヨウ化銅などが挙げられる。銅触媒の使用量は、一般式［１２］の化合物に対して0.01〜50倍モル、好ましくは、0.1〜5倍モルであればよい。
この反応に用いられるパラジウム触媒としては、たとえば、パラジウム−炭素およびパラジウム黒などの金属パラジウム；塩化パラジウムなどの無機パラジウム塩；酢酸パラジウムなどの有機パラジウム塩；テトラキス（トリフェニルホスフィン）パラジウム（０）、ビス（トリフェニルホスフィン）パラジウム（II）クロリド、１，１’−ビス（ジフェニルホスフィノ）フェロセンパラジウム（II）クロリドおよびトリス（ジベンジリデンアセトン）ジパラジウム（０）などの有機パラジウム錯体ならびにポリマー担持ビス（アセタート）トリフェニルホスフィンパラジウム（II）およびポリマー担持ジ（アセタート）ジシクロヘキシルフェニルホスフィンパラジウム（II）などのポリマー固定化有機パラジウム錯体などが挙げられ、これらは組み合わせて使用してもよい。パラジウム触媒の使用量は、一般式［１２］の化合物に対して、0.00001〜1倍モル、好ましくは、0.001〜0.1倍モルであればよい。
一般式［１４］の化合物の使用量は、一般式［１２］の化合物に対して、1〜50倍モル、好ましくは、1〜2倍モルであればよい。
この反応は、好ましくは、不活性気体（たとえば、窒素、アルゴン）雰囲気下、10〜170℃で1分間〜24時間実施すればよい。Examples of the base that is optionally used in this reaction include inorganic bases such as sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate and tripotassium phosphate, and organic bases such as triethylamine and diisopropylethylamine. The amount of the base used may be 1 to 50 times mol, preferably 2 to 5 times mol, of the compound of the general formula [12].
Examples of the copper catalyst used as desired in this reaction include copper bromide and copper iodide. The usage-amount of a copper catalyst is 0.01-50 times mole with respect to the compound of General formula [12], Preferably, what is necessary is just 0.1-5 times mole.
Examples of the palladium catalyst used in this reaction include metal palladium such as palladium-carbon and palladium black; inorganic palladium salt such as palladium chloride; organic palladium salt such as palladium acetate; tetrakis (triphenylphosphine) palladium (0), Organic palladium complexes such as bis (triphenylphosphine) palladium (II) chloride, 1,1′-bis (diphenylphosphino) ferrocenepalladium (II) chloride and tris (dibenzylideneacetone) dipalladium (0), and polymer-supported bis Examples include polymer-fixed organic palladium complexes such as (acetate) triphenylphosphine palladium (II) and polymer-supported di (acetate) dicyclohexylphenylphosphine palladium (II). It may be used in conjunction look. The usage-amount of a palladium catalyst is 0.00001-1 times mole with respect to the compound of General formula [12], Preferably, what is necessary is just 0.001-0.1 times mole.
The amount of the compound of the general formula [14] used may be 1 to 50 times mol, preferably 1 to 2 times mol for the compound of the general formula [12].
This reaction is preferably carried out at 10 to 170 ° C. for 1 minute to 24 hours in an inert gas (for example, nitrogen, argon) atmosphere.
［製造法Ｄ］
一般式［１３ｄ］の化合物は、製造法７に準じて、一般式［１３ｃ］の化合物をアルキル化することにより製造することができる。 The compound of the general formula [13d] can be produced by alkylating the compound of the general formula [13c] according to the production method 7.
［製造法Ｅ］
（Ｅ−１）
一般式［１５］の化合物は、一般式［１３］の化合物を還元することにより製造できる。この反応は、リチャード Ｃ．ラロック（Richard C. Larock）ら、コンプレヘンシブ・オーガニック・トランスフォーメーションズ（Comprehensive Organic Transformations）、1999年、第2版、p.823-827、ジョン・ウィリイ・アンド・サンズ社（John Wiley & Sons,INC.）に記載された方法またはそれに準じた方法で行えばよい。具体的には、金属触媒を用いる接触水素添加反応ならびに鉄または亜鉛などの金属を用いる還元反応などが挙げられる。
一般式［１３］の化合物を接触水素添加反応に付す場合、製造法（５−２）に準じて行えばよい。
一般式［１３］の化合物を金属を用いる還元に付す場合、使用される溶媒としては、反応に悪影響を及ぼさないものであれば特に限定されないが、たとえば、水；メタノール、エタノール、２−プロパノールおよび２−メチル−２−プロパノールなどのアルコール類；Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミドおよび１−メチル−２−ピロリドンなどのアミド類；塩化メチレン、クロロホルムおよびジクロロエタンなどのハロゲン化炭化水素類；ベンゼン、トルエンおよびキシレンなどの芳香族炭化水素類；ジオキサン、テトラヒドロフラン、アニソール、エチレングリコールジメチルエーテル、ジエチレングリコールジメチルエーテルおよびジエチレングリコールジエチルエーテルなどのエーテル類；アセトニトリルなどのニトリル類；アセトンおよび２−ブタノンなどのケトン類；酢酸エチルおよび酢酸ブチルなどのエステル類ならびに酢酸などのカルボン酸類などが挙げられ、これらは混合して使用してもよい。
この反応に用いられる金属としては、たとえば、鉄、亜鉛、スズおよび塩化スズ（II）などが挙げられる。金属の使用量は、一般式［１３］の化合物に対して、1〜50倍モル、好ましくは、1〜10倍モルであればよい。
この反応は、0〜200℃、好ましくは、0〜100℃で1分間〜24時間実施すればよい。(E-1)
The compound of the general formula [15] can be produced by reducing the compound of the general formula [13]. This reaction was performed by Richard C. Richard C. Larock et al., Comprehensive Organic Transformations, 1999, 2nd edition, p.823-827, John Wiley & Sons , INC.) Or a method similar thereto. Specific examples include a catalytic hydrogenation reaction using a metal catalyst and a reduction reaction using a metal such as iron or zinc.
What is necessary is just to perform according to a manufacturing method (5-2), when attaching | subjecting the compound of General formula [13] to catalytic hydrogenation reaction.
When the compound of the general formula [13] is subjected to reduction using a metal, the solvent used is not particularly limited as long as it does not adversely influence the reaction. For example, water; methanol, ethanol, 2-propanol and Alcohols such as 2-methyl-2-propanol; amides such as N, N-dimethylformamide, N, N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane Aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as dioxane, tetrahydrofuran, anisole, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and diethylene glycol diethyl ether; acetonitrile What nitriles, ketones such as acetone and 2-butanone; and esters and carboxylic acids such as acetic acid such as ethyl acetate and butyl acetate and the like, may be used which are mixed.
Examples of the metal used in this reaction include iron, zinc, tin, and tin (II) chloride. The amount of the metal used may be 1 to 50 times mol, preferably 1 to 10 times mol, of the compound of the general formula [13].
This reaction may be carried out at 0 to 200 ° C., preferably 0 to 100 ° C. for 1 minute to 24 hours.
（Ｅ−２）
一般式［２］の化合物は、製造法６に準じて、一般式［１５］の化合物をアミド化することにより製造することができる。(E-2)
The compound of the general formula [2] can be produced by amidating the compound of the general formula [15] according to the production method 6.
［製造法Ｆ］
一般式［１６］の化合物として、たとえば、５−クロロ−２−ニトロアニリンおよび５−クロロ−４−メチル−２−ニトロアニリンなどが知られている。 As compounds of the general formula [16], for example, 5-chloro-2-nitroaniline and 5-chloro-4-methyl-2-nitroaniline are known.
（Ｆ−１）
一般式［１７］の化合物は、製造法６に準じて、一般式［１６］の化合物をアミド化することにより製造することができる。(F-1)
The compound of the general formula [17] can be produced by amidating the compound of the general formula [16] according to the production method 6.
（Ｆ−２）
一般式［１８］の化合物は、製造法２に準じて、一般式［１７］の化合物を一般式［４ａ］または一般式［４ｂ］の化合物と反応させることにより製造することができる。(F-2)
The compound of the general formula [18] can be produced by reacting the compound of the general formula [17] with the compound of the general formula [4a] or the general formula [4b] according to the production method 2.
（Ｆ−３）
一般式［２ａ］の化合物は、製造法（Ｅ−１）に準じて、一般式［１８］の化合物を還元することにより製造することができる。(F-3)
The compound of the general formula [2a] can be produced by reducing the compound of the general formula [18] according to the production method (E-1).
［製造法Ｇ］
一般式［１９］の化合物として、たとえば、４−ブロモ−１−フルオロ−２−ニトロベンゼンなどが知られている。 As a compound of general formula [19], for example, 4-bromo-1-fluoro-2-nitrobenzene and the like are known.
（Ｇ−１）
一般式［２０］の化合物は、製造法２に準じて、一般式［１９］の化合物を一般式［４ａ］または一般式［４ｂ］の化合物と反応させることにより製造することができる。(G-1)
The compound of general formula [20] can be produced by reacting the compound of general formula [19] with the compound of general formula [4a] or general formula [4b] according to production method 2.
（Ｇ−２）
一般式［２１］の化合物として、たとえば、メチルアミン、エチルアミンおよびシクロプロピルアミンなどが知られている。
一般式［２２］の化合物は、塩基の存在下または不存在下、一般式［２０］の化合物を一般式［２１］の化合物と反応させることにより製造することができる。(G-2)
As the compound of the general formula [21], for example, methylamine, ethylamine, cyclopropylamine and the like are known.
The compound of the general formula [22] can be produced by reacting the compound of the general formula [20] with the compound of the general formula [21] in the presence or absence of a base.
この反応で使用される溶媒としては、反応に悪影響を及ぼさないものであれば特に限定されないが、たとえば、水；メタノール、エタノール、２−プロパノールおよび２−メチル−２−プロパノールなどのアルコール類；ベンゼン、トルエンおよびキシレンなどの芳香族炭化水素類；Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミドおよび１−メチル−２−ピロリドンなどのアミド類；塩化メチレン、クロロホルムおよびジクロロエタンなどのハロゲン化炭化水素類；ジオキサン、テトラヒドロフラン、アニソール、エチレングリコールジメチルエーテル、ジエチレングリコールジメチルエーテルおよびジエチレングリコールジエチルエーテルなどのエーテル類；アセトンおよび２−ブタノンなどのケトン類；アセトニトリルなどのニトリル類；酢酸エチルおよび酢酸ブチルなどのエステル類ならびにジメチルスルホキシドなどのスルホキシド類などが挙げられ、これらは混合して使用してもよい。 The solvent used in this reaction is not particularly limited as long as it does not adversely influence the reaction. For example, water; alcohols such as methanol, ethanol, 2-propanol and 2-methyl-2-propanol; benzene , Aromatic hydrocarbons such as toluene and xylene; amides such as N, N-dimethylformamide, N, N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane Ethers such as dioxane, tetrahydrofuran, anisole, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and diethylene glycol diethyl ether; ketones such as acetone and 2-butanone; acetonitrile What nitriles; and esters and sulfoxides such as dimethyl sulfoxide, such as ethyl acetate and butyl acetate and the like, may be used which are mixed.
この反応において所望により用いられる塩基としては、たとえば、炭酸水素ナトリウム、炭酸ナトリウム、炭酸カリウム、炭酸セシウムおよびリン酸三カリウムなどの無機塩基ならびにピリジン、４−（ジメチルアミノ）ピリジン、トリエチルアミンおよびジイソプロピルエチルアミンなどの有機塩基が挙げられる。塩基の使用量は、一般式［２０］の化合物に対して1〜50倍モル、好ましくは、2〜5倍モルであればよい。 Examples of the base optionally used in this reaction include inorganic bases such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate, cesium carbonate and tripotassium phosphate, and pyridine, 4- (dimethylamino) pyridine, triethylamine and diisopropylethylamine. Of the organic base. The amount of the base used may be 1 to 50 times mol, preferably 2 to 5 times mol, of the compound of the general formula [20].
一般式［２１］の化合物の使用量は、一般式［２０］の化合物に対して、1〜50倍モル、好ましくは、1〜5倍モルであればよい。
この反応は、好ましくは、10〜170℃で1分間〜96時間実施すればよい。The amount of the compound of the general formula [21] used may be 1 to 50 times mol, preferably 1 to 5 times mol, of the compound of the general formula [20].
This reaction is preferably carried out at 10 to 170 ° C. for 1 minute to 96 hours.
（Ｇ−３）
一般式［２３］の化合物は、製造法（Ｅ−１）に準じて、一般式［２２］の化合物を還元することにより製造することができる。(G-3)
The compound of the general formula [23] can be produced by reducing the compound of the general formula [22] according to the production method (E-1).
（Ｇ−４）
一般式［２ｂ］の化合物は、製造法６に準じて、一般式［２３］の化合物をアミド化することにより製造することができる。(G-4)
The compound of the general formula [2b] can be produced by amidating the compound of the general formula [23] according to the production method 6.
［製造法Ｈ］
（Ｈ−１）
一般式［２４］の化合物は、製造法１に準じて、一般式［１２］の化合物をスルホンアミド化することにより製造することができる。(H-1)
The compound of the general formula [24] can be produced by sulfonamidating the compound of the general formula [12] according to the production method 1.
（Ｈ−２）
一般式［２５］の化合物は、製造法（Ｅ−１）に準じて、一般式［２４］の化合物を還元することにより製造することができる。(H-2)
The compound of the general formula [25] can be produced by reducing the compound of the general formula [24] according to the production method (E-1).
（Ｈ−３）
一般式［３］の化合物は、製造法６に準じて、一般式［２５］の化合物をアミド化することにより製造することができる。(H-3)
The compound of the general formula [3] can be produced by amidating the compound of the general formula [25] according to the production method 6.
［製造法Ｉ］
一般式［２６ａ］の化合物は、製造法２に準じて、一般式［２４］の化合物を一般式［４ａ］または一般式［４ｂ］の化合物と反応させることにより製造することができる。 The compound of the general formula [26a] can be produced by reacting the compound of the general formula [24] with the compound of the general formula [4a] or the general formula [4b] according to the production method 2.
［製造法Ｊ］
一般式［２６ｂ］の化合物は、製造法２に準じて、一般式［２４］の化合物を一般式［６］の化合物と反応させることにより製造することができる。 The compound of the general formula [26b] can be produced by reacting the compound of the general formula [24] with the compound of the general formula [6] according to the production method 2.
［製造法Ｋ］
一般式［２６ｃ］の化合物は、製造法Ｃに準じて、一般式［２４］の化合物を一般式［１４］の化合物と反応させることにより製造することができる。 The compound of the general formula [26c] can be produced by reacting the compound of the general formula [24] with the compound of the general formula [14] according to the production method C.
［製造法Ｌ］
（Ｌ−１）
一般式［２６］の化合物は、製造法１に準じて、一般式［１３］の化合物をスルホンアミド化することにより製造することができる。(L-1)
The compound of the general formula [26] can be produced by sulfonamidating the compound of the general formula [13] according to the production method 1.
（Ｌ−２）
一般式［８］の化合物は、製造法（Ｅ−１）に準じて、一般式［２６］の化合物を還元することにより製造することができる。(L-2)
The compound of the general formula [8] can be produced by reducing the compound of the general formula [26] according to the production method (E-1).
［製造法Ｍ］
（Ｍ−１）
一般式［２７］の化合物は、一般式［１６］の化合物のアミノ基を保護することによって、製造することができる。たとえば、Ｗ．グリーン（W.Greene）ら、プロテクティブ・グループス・イン・オーガニック・シンセシス（Protective Groups in Organic Synthesis）第3版、1999年、p.494-615、ジョン・ウィリイ・アンド・サンズ社（John Wiley & Sons,INC.）に記載の方法などによって行うことができる。(M-1)
The compound of the general formula [27] can be produced by protecting the amino group of the compound of the general formula [16]. For example, W.W. W. Greene et al., Protective Groups in Organic Synthesis, 3rd edition, 1999, p.494-615, John Wiley & Sons, INC.).
（Ｍ−２）
一般式［２８］の化合物は、製造法２に準じて、一般式［２７］の化合物を一般式［４ａ］または一般式［４ｂ］の化合物と反応させることにより製造することができる。(M-2)
The compound of general formula [28] can be produced by reacting the compound of general formula [27] with the compound of general formula [4a] or general formula [4b] according to production method 2.
（Ｍ−３）
一般式［２９］の化合物は、製造法（Ｅ−１）に準じて、一般式［２８］の化合物を還元することにより製造することができる。(M-3)
The compound of the general formula [29] can be produced by reducing the compound of the general formula [28] according to the production method (E-1).
（Ｍ−４）
一般式［３０］の化合物は、製造法１に準じて、一般式［２９］の化合物をスルホンアミド化することにより製造することができる。(M-4)
The compound of the general formula [30] can be produced by sulfonamidating the compound of the general formula [29] according to the production method 1.
（Ｍ−５）
一般式［３１］の化合物は、製造法７に準じて、一般式［３０］の化合物をアルキル化することにより製造することができる。(M-5)
The compound of the general formula [31] can be produced by alkylating the compound of the general formula [30] according to the production method 7.
（Ｍ−６）
一般式［８ａ］の化合物は、一般式［３１］の化合物を脱保護することによって、製造することができる。たとえば、Ｗ．グリーン（W.Greene）ら、プロテクティブ・グループス・イン・オーガニック・シンセシス（Protective Groups in Organic Synthesis）第3版、1999年、p.494-615、ジョン・ウィリイ・アンド・サンズ社（John Wiley & Sons,INC.）に記載の方法などによって行うことができる。(M-6)
The compound of the general formula [8a] can be produced by deprotecting the compound of the general formula [31]. For example, W.W. W. Greene et al., Protective Groups in Organic Synthesis, 3rd edition, 1999, p.494-615, John Wiley & Sons, INC.).
［製造法Ｎ］
一般式［３２］の化合物として、たとえば、ビス（ピナコラート）ジボロン、ビス（ネオペンチルグリラート）ジボロンおよびビス（ヘキシレングリコラート）ジボロンなどが知られている。 As the compound of the general formula [32], for example, bis (pinacolato) diboron, bis (neopentylglylate) diboron, bis (hexylene glycolate) diboron and the like are known.
一般式［１０］の化合物は、製造法２に準じて、一般式［３］の化合物を一般式［３２］の化合物と反応させることにより製造することができる。 The compound of general formula [10] can be produced by reacting the compound of general formula [3] with the compound of general formula [32] according to production method 2.
［製造法Ｏ］
一般式［３３］の化合物として、たとえば、５−クロロ−４−ヨード−２−ニトロアニリンなどが知られている。 As a compound of the general formula [33], for example, 5-chloro-4-iodo-2-nitroaniline and the like are known.
（Ｏ−１）
一般式［３４］の化合物は、塩基の存在下、一般式［３３］の化合物をアルコールと反応させることにより製造することができる。(O-1)
The compound of the general formula [34] can be produced by reacting the compound of the general formula [33] with an alcohol in the presence of a base.
この反応で使用される溶媒としては、反応に悪影響を及ぼさないものであれば特に限定されないが、たとえば、ベンゼン、トルエンおよびキシレンなどの芳香族炭化水素類；Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミドおよび１−メチル−２−ピロリドンなどのアミド類；塩化メチレン、クロロホルムおよびジクロロエタンなどのハロゲン化炭化水素類；ジオキサン、テトラヒドロフラン、アニソール、エチレングリコールジメチルエーテル、ジエチレングリコールジメチルエーテルおよびジエチレングリコールジエチルエーテルなどのエーテル類；アセトンおよび２−ブタノンなどのケトン類；アセトニトリルなどのニトリル類；酢酸エチルおよび酢酸ブチルなどのエステル類ならびにジメチルスルホキシドなどのスルホキシド類などが挙げられ、これらは混合して使用してもよい。 The solvent used in this reaction is not particularly limited as long as it does not adversely influence the reaction. For example, aromatic hydrocarbons such as benzene, toluene and xylene; N, N-dimethylformamide, N, N Amides such as dimethylacetamide and 1-methyl-2-pyrrolidone; Halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; Ethers such as dioxane, tetrahydrofuran, anisole, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and diethylene glycol diethyl ether Ketones such as acetone and 2-butanone; nitriles such as acetonitrile; esters such as ethyl acetate and butyl acetate; and sulfones such as dimethyl sulfoxide; Kishido such, and the like, it may be used which are mixed.
この反応において所望により用いられる塩基としては、たとえば、水酸化ナトリウム、水酸化カリウム、炭酸水素ナトリウム、炭酸ナトリウム、炭酸カリウム、炭酸セシウムおよびリン酸三カリウムなどの無機塩基ならびにピリジン、４−（ジメチルアミノ）ピリジン、トリエチルアミンおよびジイソプロピルエチルアミンなどの有機塩基が挙げられる。塩基の使用量は、一般式［３３］の化合物に対して1〜50倍モル、好ましくは、2〜10倍モルであればよい。 Bases optionally used in this reaction include, for example, inorganic bases such as sodium hydroxide, potassium hydroxide, sodium hydrogen carbonate, sodium carbonate, potassium carbonate, cesium carbonate and tripotassium phosphate, and pyridine, 4- (dimethylamino ) Organic bases such as pyridine, triethylamine and diisopropylethylamine. The amount of the base used may be 1 to 50 times mol, preferably 2 to 10 times mol, of the compound of the general formula [33].
この反応において所望により用いられるアルコールとしては、たとえば、メタノール、ｔ−ブチルアルコールおよびベンジルアルコールなどが挙げられる。アルコールの使用量は、一般式［３３］の化合物に対して1〜100倍モル、好ましくは、1〜30倍モルであればよい。
この反応は、好ましくは、10〜170℃で1分間〜96時間実施すればよい。Examples of the alcohol that is optionally used in this reaction include methanol, t-butyl alcohol, and benzyl alcohol. The amount of alcohol used may be 1 to 100 times mol, preferably 1 to 30 times mol, of the compound of general formula [33].
This reaction is preferably carried out at 10 to 170 ° C. for 1 minute to 96 hours.
（Ｏ−２）
一般式［３５］の化合物は、製造法（Ｍ−１）に準じて、一般式［３４］の化合物のアミノ基を保護することによって製造することができる。(O-2)
The compound of general formula [35] can be manufactured by protecting the amino group of the compound of general formula [34] according to a manufacturing method (M-1).
（Ｏ−３）
一般式［３６］の化合物は、製造法２に準じて、一般式［３５］の化合物を一般式［４ａ］または一般式［４ｂ］の化合物と反応させることにより製造することができる。(O-3)
The compound of general formula [36] can be produced by reacting the compound of general formula [35] with the compound of general formula [4a] or general formula [4b] according to Production Method 2.
（Ｏ−４）
一般式［３７］の化合物は、製造法（Ｅ−１）に準じて、一般式［３６］の化合物を還元することにより製造することができる。(O-4)
The compound of the general formula [37] can be produced by reducing the compound of the general formula [36] according to the production method (E-1).
（Ｏ−５）
一般式［３８］の化合物は、製造法６に準じて、一般式［３７］の化合物をアミド化することにより製造することができる。(O-5)
The compound of general formula [38] can be produced by amidating the compound of general formula [37] according to production method 6.
（Ｏ−６）
一般式［２ｃ］の化合物は、製造法（Ｍ−６）に準じて、一般式［３８］の化合物を脱保護することによって製造することができる。(O-6)
The compound of the general formula [2c] can be produced by deprotecting the compound of the general formula [38] according to the production method (M-6).
上記した製造法で使用される化合物において、塩の形態を取り得る化合物は、塩として使用することもできる。それらの塩としては、たとえば、一般式［１］の化合物の塩と同様の塩が挙げられる。 Among the compounds used in the above-described production method, a compound that can take the form of a salt can also be used as a salt. Examples of such salts include the same salts as the salts of the compound of the general formula [1].
上記した製造法で使用される化合物において、異性体（たとえば、光学異性体、幾何異性体および互変異性体など）が存在する場合、これらの異性体も使用することができる。また、溶媒和物、水和物および種々の形状の結晶が存在する場合、これらの溶媒和物、水和物および種々の形状の結晶も使用することができる。また、上記した製造法で使用される化合物において、保護し得る置換基、たとえば、アミノ基、ヒドロキシル基またはカルボキシル基などを有している化合物は、予めこれらの基を通常の保護基で保護しておき、反応後、自体公知の方法でこれらの保護基を脱離することもできる。 In the compound used in the above-described production method, when isomers (for example, optical isomers, geometric isomers, tautomers, etc.) exist, these isomers can also be used. Also, when solvates, hydrates and crystals of various shapes are present, these solvates, hydrates and crystals of various shapes can also be used. In addition, in the compounds used in the above-described production method, a compound having a substituent that can be protected, such as an amino group, a hydroxyl group, or a carboxyl group, is previously protected with a normal protecting group. In addition, after the reaction, these protecting groups can be removed by a method known per se.
本発明化合物を医薬として用いる場合、通常、製剤化に使用される賦形剤、担体および希釈剤などの製剤補助剤を適宜混合してもよい。これらは常法にしたがって、錠剤、カプセル剤、散剤、シロップ剤、顆粒剤、丸剤、懸濁剤、乳剤、液剤、粉体製剤、坐剤、点眼剤、点鼻剤、点耳剤、貼付剤、軟膏剤または注射剤などの形態で経口または非経口で投与することができる。また投与方法、投与量および投与回数は、患者の年齢、体重および症状に応じて適宜選択することができる。通常、成人に対しては、経口または非経口（たとえば、注射、点滴および直腸部位への投与など）投与により、１日、0.01〜1000mg/kgを１回から数回に分割して投与すればよい。 When the compound of the present invention is used as a pharmaceutical, formulation adjuvants such as excipients, carriers, and diluents that are usually used for formulation may be appropriately mixed. These are tablets, capsules, powders, syrups, granules, pills, suspensions, emulsions, solutions, powder formulations, suppositories, eye drops, nasal drops, ear drops, patches in accordance with conventional methods. It can be administered orally or parenterally in the form of an agent, ointment or injection. In addition, the administration method, the dosage, and the number of administrations can be appropriately selected according to the age, weight and symptoms of the patient. Usually, for adults, oral administration or parenteral administration (for example, injection, infusion, administration to the rectal site, etc.), 0.01 to 1000 mg / kg is administered in 1 to several divided doses per day. Good.
次に、本発明の代表的化合物の有用性を以下の試験例で説明する。 Next, the usefulness of the representative compounds of the present invention will be described in the following test examples.
試験例１ ＰＧＥ２産生阻害試験
Ｊａｇｇｉらの方法（インフラメーション・リサーチ（Inflammation Research）、2004年、第53巻、p.150-157）に準じ、ＰＧＥ２産生阻害作用を測定した。
ヒト単球由来細胞株THP-1細胞1.0×105個を2-mercaptoethanol（50μM）を含む10％ウシ胎児血清添加RPMI1640培地（以下、培地とする）0.1mLに懸濁して96ウェルプレートに播種し、ホルボールミリステートアセテート（Phorbol 12-myristate 13-acetate）（100ng/mL）存在下、37℃、5％CO2、95％空気の条件下で2日間培養し、細胞をマクロファージに分化誘導した。得られた細胞を試験化合物を含有する培地で1時間培養した後、リポポリサッカライド（Lipopolysaccharide（E. coli 0111:B4）、シグマ）（3μg/mL）で刺激し、24時間培養後に培地上清を回収した。なお、試験化合物はDMSOに溶解し、培地で500倍希釈して使用した。培地上清中のＰＧＥ２量をELISAキット（Prostaglandin E2 EIA Kit-Monoclonal、Cayman Chemical）で定量し、試験化合物不存在下で得られるＰＧＥ２量を100％として、試験化合物存在下で得られるＰＧＥ２量から阻害率を算出した。ＰＧＥ２量が検出限界値以下の場合は、検出限界値とした。
結果を表７に示す。Test Example 1 PGE 2 Production Inhibition Test PGE 2 production inhibitory activity was measured according to the method of Jagi et al. (Inflammation Research, 2004, Vol. 53, p. 150-157).
Suspend in a 96-well plate by suspending 1.0 × 10 5 human monocyte-derived cell line THP-1 cells in 0.1 mL of RPMI1640 medium (hereinafter referred to as medium) containing 10% fetal bovine serum containing 2-mercaptoethanol (50 μM) Then, in the presence of phorbol myristate acetate (Phorbol 12-myristate 13-acetate) (100 ng / mL), the cells are cultured for 2 days under conditions of 37 ° C, 5% CO 2 , and 95% air to induce differentiation of the cells into macrophages. did. After culturing the obtained cells in a medium containing the test compound for 1 hour, the cells were stimulated with lipopolysaccharide (Lipopolysaccharide (E. coli 0111: B4), sigma) (3 μg / mL) and cultured for 24 hours. Was recovered. The test compound was dissolved in DMSO and used after diluting 500 times with a medium. The amount of PGE 2 in the culture supernatant is quantified with an ELISA kit (Prostaglandin E 2 EIA Kit-Monoclonal, Cayman Chemical) and obtained in the presence of the test compound with the amount of PGE 2 obtained in the absence of the test compound as 100%. inhibition rate was calculated using the PGE 2 content. When the amount of PGE 2 was not more than the detection limit value, it was set as the detection limit value.
The results are shown in Table 7.
試験例２ ラットアジュバント関節炎
ラットアジュバント関節炎に対する試験化合物の治療効果を評価した。即ち、流動パラフィンで6mg/mLに懸濁した結核死菌（M.Tuberculosis H37RA、DIFCO）0.1mLを雄性LEW系ラット（5または6週齢、一群5匹）（日本チャールス・リバー）の尾根部に接種してアジュバント関節炎を惹起した。接種18日後にプレシスモメーター（Plethysmometer（Ugo Basile））を用いて両後肢の足容積を測定し、両後肢の平均足容積がほぼ均一になるように群分けした。試験化合物を0.5％メチルセルロース水溶液に懸濁し、接種18日後（投与開始日）から接種22日後（投与終了日）まで1日1回経口投与した。なお、対照群には、0.5％メチルセルロース水溶液を同様に投与した。投与開始日及び投与終了日の腫脹率（％）（式−１）をそれぞれ対応する正常群の平均足容積から算出し、投与開始日の腫脹率を100として腫脹率変化率（％）（式−２）を求め、抑制率（％）（式−３）で試験化合物の有効性を評価した。
式−１ 腫脹率（％）＝（足容積／正常群の平均足容積−１）×100
式−２ 腫脹率変化率（％）＝投与終了日の腫脹率（％）／投与開始日の腫脹率（％）×100
式−３ 抑制率（％）＝（１−試験化合物投与群の腫脹率変化率（％）／対照群の腫脹率変化率（％））×100
実施例1の化合物は、10mg/kgで抑制率37％であり、優れた抗腫脹作用を示した。同様に実施例81、127および170（塩酸塩）の化合物は、10mg/kgで優れた抗腫脹作用を示した。Test Example 2 Rat Adjuvant Arthritis The therapeutic effect of the test compound on rat adjuvant arthritis was evaluated. That is, 0.1 mL of tuberculosis killed bacteria (M.Tuberculosis H37RA, DIFCO) suspended in liquid paraffin at 6 mg / mL was added to the ridge of male LEW rats (5 or 6 weeks of age, 5 per group) (Charles River Japan) To inoculate adjuvant arthritis. 18 days after the inoculation, the foot volumes of both hind limbs were measured using a plethysmometer (Plethysmometer (Ugo Basile)), and the groups were divided so that the average foot volumes of both hind limbs were almost uniform. The test compound was suspended in an aqueous 0.5% methylcellulose solution and orally administered once a day from 18 days after the inoculation (day of administration start) to 22 days after the inoculation (day of administration end). The control group was similarly administered with a 0.5% methylcellulose aqueous solution. The swelling rate (%) (formula-1) on the administration start date and the administration end date was calculated from the average foot volume of the corresponding normal group, and the swelling rate change rate (%) (equation) with the swelling rate on the administration start date as 100 -2), and the effectiveness of the test compound was evaluated by the inhibition rate (%) (formula-3).
Formula-1 swelling rate (%) = (foot volume / average foot volume of normal group-1) × 100
Formula-2 Swelling rate change rate (%) = swelling rate (%) at the end of administration / swelling rate (%) at the start of administration × 100
Formula-3 Inhibition rate (%) = (1-Expansion rate change rate of test compound administration group (%) / Control group change rate of swelling rate (%)) × 100
The compound of Example 1 showed an excellent anti-swelling action with an inhibition rate of 37% at 10 mg / kg. Similarly, the compounds of Examples 81, 127 and 170 (hydrochloride) showed excellent anti-swelling action at 10 mg / kg.
次に、本発明を参考例および実施例を挙げて説明するが、本発明はこれらに限定されるものではない。
溶離液における混合比は、容量比である。特に記載のない場合、シリカゲルカラムクロマトグラフィーにおける担体は、富士シリシア化学株式会社、ＰＳＱ１００Ｂ（球状）；逆相シリカゲルカラムクロマトグラフィーにおける担体は、株式会社ワイエムシイ、ＯＤＳ−ＡＭ１２Ｓ０５−２５２０ＷＴである。
各実施例において各略号は、以下の意味を有する。
Ａｃ：アセチル、Ｂｏｃ：ｔｅｒｔ−ブトキシカルボニル、Ｂｎ：ベンジル、ｔＢｕ：ｔｅｒｔ−ブチル、Ｂｚ：ベンゾイル、Ｅｔ：エチル、Ｍｅ：メチル
DMSO-d6：重ジメチルスルホキシドNext, the present invention will be described with reference examples and examples, but the present invention is not limited to these examples.
The mixing ratio in the eluent is a volume ratio. Unless otherwise specified, the carrier in silica gel column chromatography is Fuji Silysia Chemical Co., Ltd., PSQ100B (spherical); the carrier in reverse phase silica gel column chromatography is YMC, Inc., ODS-AM12S05-2520WT.
In each example, each abbreviation has the following meaning.
Ac: acetyl, Boc: tert-butoxycarbonyl, Bn: benzyl, t Bu: tert-butyl, Bz: benzoyl, Et: ethyl, Me: methyl
DMSO-d 6 : Heavy dimethyl sulfoxide
参考例１
1H-NMR(CDCl3)δ値：2.42(3H,s),3.02(3H,d,J=5.6Hz),7.08-7.22(1H,broad),7.38(1H,d,J=2.2Hz),8.07(1H,d,J=2.2Hz).Reference example 1
1 H-NMR (CDCl 3 ) δ value: 2.42 (3H, s), 3.02 (3H, d, J = 5.6 Hz), 7.08-7.22 (1H, broad), 7.38 (1H, d, J = 2.2 Hz) , 8.07 (1H, d, J = 2.2Hz).
参考例２
２−（ベンジルオキシ）−Ｎ−メチル−６−ニトロ−４−フェニルアニリン
1H-NMR(CDCl3)δ値：3.20(3H,d,J=5.6Hz),5.14(2H,s),7.25(1H,d,J=1.9Hz),7.30-7.53(10H,m),7.66-7.73(1H,broad),7.99(1H,d,J=1.9Hz).Reference example 2
2- (Benzyloxy) -N-methyl-6-nitro-4-phenylaniline
1 H-NMR (CDCl 3 ) δ value: 3.20 (3H, d, J = 5.6 Hz), 5.14 (2H, s), 7.25 (1H, d, J = 1.9 Hz), 7.30-7.53 (10H, m) , 7.66-7.73 (1H, broad), 7.99 (1H, d, J = 1.9Hz).
参考例３
1H-NMR(DMSO-d6)δ値：2.93(3H,d,J=4.9Hz),7.02(1H,d,J=12.2Hz),8.34(1H,d,J=7.3Hz),8.34-8.40(1H,broad).Reference example 3
1 H-NMR (DMSO-d 6 ) δ value: 2.93 (3H, d, J = 4.9 Hz), 7.02 (1H, d, J = 12.2 Hz), 8.34 (1H, d, J = 7.3 Hz), 8.34 -8.40 (1H, broad).
参考例４
1H-NMR(CDCl3)δ値：3.04(3H,d,J=5.2Hz),3.96(3H,s),6.06(1H,s),8.28-8.40(1H,broad),8.60(1H,s).Reference example 4
1 H-NMR (CDCl 3 ) δ value: 3.04 (3H, d, J = 5.2 Hz), 3.96 (3H, s), 6.06 (1H, s), 8.28-8.40 (1H, broad), 8.60 (1H, s).
参考例５
1H-NMR(DMSO-d6)δ値：3.01(3H,d,J=4.9Hz),7.11(1H,d,J=9.0Hz),7.31-7.36(1H,m),7.42-7.48(2H,m),7.63-7.68(2H,m),7.93(1H,dd,J=9.0,2.4Hz),8.22-8.29(1H,broad),8.32(1H,d,J=2.4Hz).Reference Example 5
1 H-NMR (DMSO-d 6 ) δ value: 3.01 (3H, d, J = 4.9 Hz), 7.11 (1H, d, J = 9.0 Hz), 7.31-7.36 (1H, m), 7.42-7.48 ( 2H, m), 7.63-7.68 (2H, m), 7.93 (1H, dd, J = 9.0, 2.4Hz), 8.22-8.29 (1H, broad), 8.32 (1H, d, J = 2.4Hz).
参考例６
1H-NMR(DMSO-d6)δ値：2.36(3H,s),2.78(3H,d,J=5.4Hz),6.46-6.55(1H,m),7.29-7.34(1H,m),7.41-7.46(2H,m),7.62-7.66(2H,m),7.68-7.71(1H,m),7.89(1H,d,J=2.2Hz).Reference Example 6
1 H-NMR (DMSO-d 6 ) δ value: 2.36 (3H, s), 2.78 (3H, d, J = 5.4 Hz), 6.46-6.55 (1H, m), 7.29-7.34 (1H, m), 7.41-7.46 (2H, m), 7.62-7.66 (2H, m), 7.68-7.71 (1H, m), 7.89 (1H, d, J = 2.2Hz).
参考例７
1H-NMR(CDCl3)δ値：5.20(2H,s),6.40-6.60(2H,broad),7.25(1H,d,J=2.0Hz),7.30-7.55(10H,m),8.02(1H,d,J=2.0Hz).Reference Example 7
1 H-NMR (CDCl 3 ) δ value: 5.20 (2H, s), 6.40-6.60 (2H, broad), 7.25 (1H, d, J = 2.0 Hz), 7.30-7.55 (10H, m), 8.02 ( (1H, d, J = 2.0Hz).
参考例８
1H-NMR(DMSO-d6)δ値：2.99(3H,d,J=4.9Hz),6.94(1H,d,J=13.9Hz),7.36-7.42(1H,m),7.44-7.56(4H,m),8.21(1H,d,J=8.5Hz),8.32-8.38(1H,broad).Reference Example 8
1 H-NMR (DMSO-d 6 ) δ value: 2.99 (3H, d, J = 4.9 Hz), 6.94 (1H, d, J = 13.9 Hz), 7.36-7.42 (1H, m), 7.44-7.56 ( 4H, m), 8.21 (1H, d, J = 8.5Hz), 8.32-8.38 (1H, broad).
参考例９
1H-NMR(DMSO-d6)δ値：3.10(3H,d,J=4.6Hz),7.35-7.41(1H,m),7.45-7.52(2H,m),7.70-7.75(2H,m),8.55-8.60(1H,m),8.61(1H,d,J=2.4Hz),8.90(1H,d,J=2.4Hz).Reference Example 9
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, d, J = 4.6Hz), 7.35-7.41 (1H, m), 7.45-7.52 (2H, m), 7.70-7.75 (2H, m ), 8.55-8.60 (1H, m), 8.61 (1H, d, J = 2.4Hz), 8.90 (1H, d, J = 2.4Hz).
参考例１０
1H-NMR(CDCl3)δ値：3.07(3H,d,J=5.4Hz),6.88(1H,d,J=9.0Hz),7.00(2H,s),7.23-7.28(1H,m),7.32-7.39(2H,m),7.46-7.51(2H,m),7.70(1H,dd,J=8.9,2.2Hz),8.10-8.19(1H,broad),8.29(1H,d,J=2.2Hz).Reference Example 10
1 H-NMR (CDCl 3 ) δ value: 3.07 (3H, d, J = 5.4 Hz), 6.88 (1H, d, J = 9.0 Hz), 7.00 (2H, s), 7.23-7.28 (1H, m) , 7.32-7.39 (2H, m), 7.46-7.51 (2H, m), 7.70 (1H, dd, J = 8.9,2.2Hz), 8.10-8.19 (1H, broad), 8.29 (1H, d, J = 2.2Hz).
参考例１１
1H-NMR(DMSO-d6)δ値：3.06(3H,s),3.26(3H,s),7.78(1H,d,J=8.7Hz),8.01(1H,dd,J=8.7,2.3Hz),8.23(1H,d,J=2.3z).Reference Example 11
1 H-NMR (DMSO-d 6 ) δ value: 3.06 (3H, s), 3.26 (3H, s), 7.78 (1H, d, J = 8.7 Hz), 8.01 (1H, dd, J = 8.7, 2.3 Hz), 8.23 (1H, d, J = 2.3z).
参考例１２
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.32(3H,s),7.44-7.56(3H,m),7.77-7.82(2H,m),7.89(1H,d,J=8.3Hz),8.08(1H,dd,J=8.3,2.2Hz),8.21(1H,d,J=2.2Hz).Reference Example 12
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.32 (3H, s), 7.44-7.56 (3H, m), 7.77-7.82 (2H, m), 7.89 (1H, d , J = 8.3Hz), 8.08 (1H, dd, J = 8.3,2.2Hz), 8.21 (1H, d, J = 2.2Hz).
参考例１３
1H-NMR(CDCl3)δ値：2.86(3H,s),3.32(3H,s),5.26(2H,s),7.36-7.56(11H,m),7.61(1H,d,J=1.9Hz).Reference Example 13
1 H-NMR (CDCl 3 ) δ value: 2.86 (3H, s), 3.32 (3H, s), 5.26 (2H, s), 7.36-7.56 (11H, m), 7.61 (1H, d, J = 1.9 Hz).
参考例１４
Ｎ−（４−ヨード−５−メトキシ−２−ニトロフェニル）−Ｎ−メチルメタンスルホンアミド
1H-NMR(CDCl3)δ値：3.04(3H,s),3.29(3H,s),3.99(3H,s),6.93(1H,s),8.48(1H,s).Reference Example 14
N- (4-Iodo-5-methoxy-2-nitrophenyl) -N-methylmethanesulfonamide
1 H-NMR (CDCl 3 ) δ value: 3.04 (3H, s), 3.29 (3H, s), 3.99 (3H, s), 6.93 (1H, s), 8.48 (1H, s).
参考例１５
1H-NMR(CDCl3)δ値：3.07(3H,s),3.34(3H,s),7.40(1H,d,J=10.2Hz),7.44-7.59(5H,m),8.09(1H,d,J=7.6Hz).Reference Example 15
1 H-NMR (CDCl 3 ) δ value: 3.07 (3H, s), 3.34 (3H, s), 7.40 (1H, d, J = 10.2 Hz), 7.44-7.59 (5H, m), 8.09 (1H, d, J = 7.6Hz).
参考例１６
1H-NMR(CDCl3)δ値：3.02(3H,s),3.32(3H,s),7.08(1H,d,J=16.4Hz),7.20(1H,d,J=16.4Hz),7.30-7.36(1H,m),7.37-7.43(2H,m),7.51-7.57(3H,m),7.73(1H,dd,J=8.3,2.1Hz),8.01(1H,d,J=2.1Hz).Reference Example 16
1 H-NMR (CDCl 3 ) δ value: 3.02 (3H, s), 3.32 (3H, s), 7.08 (1H, d, J = 16.4Hz), 7.20 (1H, d, J = 16.4Hz), 7.30 -7.36 (1H, m), 7.37-7.43 (2H, m), 7.51-7.57 (3H, m), 7.73 (1H, dd, J = 8.3,2.1Hz), 8.01 (1H, d, J = 2.1Hz ).
参考例１７
1H-NMR(DMSO-d6)δ値：3.16(3H,s),3.35(3H,s),7.49-7.59(3H,m),7.85-7.90(2H,m),8.73(1H,d,J=2.2Hz),9.13(1H,d,J=2.2Hz).Reference Example 17
1 H-NMR (DMSO-d 6 ) δ value: 3.16 (3H, s), 3.35 (3H, s), 7.49-7.59 (3H, m), 7.85-7.90 (2H, m), 8.73 (1H, d , J = 2.2Hz), 9.13 (1H, d, J = 2.2Hz).
参考例１８
1H-NMR(DMSO-d6)δ値：3.07(3H,s),3.29(3H,s),6.34(2H,t,J=2.2Hz),7.56(2H,t,J=2.2Hz),7.88(1H,d,J=8.9Hz),8.01(1H,dd,J=8.9,2.8Hz),8.20(1H,d,J=2.8Hz).Reference Example 18
1 H-NMR (DMSO-d 6 ) δ value: 3.07 (3H, s), 3.29 (3H, s), 6.34 (2H, t, J = 2.2Hz), 7.56 (2H, t, J = 2.2Hz) , 7.88 (1H, d, J = 8.9Hz), 8.01 (1H, dd, J = 8.9,2.8Hz), 8.20 (1H, d, J = 2.8Hz).
参考例１９
1H-NMR(DMSO-d6)δ値：3.01(3H,s),3.22(3H,s),7.02(1H,t,J=7.1Hz),7.15-7.22(2H,m),7.29(1H,dd,J=8.8,2.7Hz),7.31-7.38(2H,m),7.41(1H,d,J=2.7Hz),7.56(1H,d,J=8.8Hz),8.83(1H,s).Reference Example 19
1 H-NMR (DMSO-d 6 ) δ value: 3.01 (3H, s), 3.22 (3H, s), 7.02 (1H, t, J = 7.1 Hz), 7.15-7.22 (2H, m), 7.29 ( 1H, dd, J = 8.8,2.7Hz), 7.31-7.38 (2H, m), 7.41 (1H, d, J = 2.7Hz), 7.56 (1H, d, J = 8.8Hz), 8.83 (1H, s ).
参考例２０
1H-NMR(CDCl3)δ値：2.98(3H,s),3.25(3H,s),4.24-4.33(2H,broad),7.00(1H,dd,J=8.0,2.0Hz),7.03(1H,d,J=2.0Hz),7.07(1H,dd,J=5.1,3.7Hz),7.13(1H,d,J=8.0Hz),7.25-7.30(2H,m).Reference Example 20
1 H-NMR (CDCl 3 ) δ value: 2.98 (3H, s), 3.25 (3H, s), 4.24–4.33 (2H, broad), 7.00 (1H, dd, J = 8.0, 2.0 Hz), 7.03 ( 1H, d, J = 2.0Hz), 7.07 (1H, dd, J = 5.1,3.7Hz), 7.13 (1H, d, J = 8.0Hz), 7.25-7.30 (2H, m).
参考例２１
Ｎ−（２−アミノ−４−（２−フルオロフェニル）フェニル）−Ｎ−メチルメタンスルホンアミド
1H-NMR(CDCl3)δ値：3.01(3H,s),3.27(3H,s),4.23-4.32(2H,broad),6.93(1H,dt,J=8.2,1.8Hz),6.97-6.99(1H,m),7.10-7.22(3H,m),7.28-7.36(1H,m),7.40(1H,td,J=7.8,1.9Hz).Reference Example 21
N- (2-amino-4- (2-fluorophenyl) phenyl) -N-methylmethanesulfonamide
1 H-NMR (CDCl 3 ) δ value: 3.01 (3H, s), 3.27 (3H, s), 4.23-4.32 (2H, broad), 6.93 (1H, dt, J = 8.2, 1.8 Hz), 6.97- 6.99 (1H, m), 7.10-7.22 (3H, m), 7.28-7.36 (1H, m), 7.40 (1H, td, J = 7.8,1.9Hz).
参考例２２
得られたＮ−（５−メトキシ−２−ニトロ−４−フェニルフェニル）−Ｎ−メチルメタンスルホンアミドの酢酸エチル4.0mLおよびメタノール2.0mL混液に10％パラジウム−炭素42mgを加え、水素雰囲気下、室温で1時間攪拌した。反応混合物に10％パラジウム−炭素85mgを加え、水素雰囲気下、室温で1時間攪拌した。反応混合物に10％パラジウム−炭素85mgを加え、水素雰囲気下、室温で2時間攪拌した。反応混合物の不溶物をろ去後、減圧下で溶媒を留去した。得られた残留物をシリカゲルカラムクロマトグラフィー［溶離液；100-50％ヘキサン／酢酸エチル］で精製し、黄色固体のＮ−（２−アミノ−５−メトキシ−４−フェニルフェニル）−Ｎ−メチルメタンスルホンアミド0.11gを得た。
1H-NMR(CDCl3)δ値：3.03(3H,s),3.28(3H,s),3.69(3H,s),3.92-4.00(2H,broad),6.77(1H,s),6.80(1H,s),7.30-7.36(1H,m),7.37-7.43(2H,m),7.45-7.50(2H,m).Reference Example 22
To a mixture of the obtained N- (5-methoxy-2-nitro-4-phenylphenyl) -N-methylmethanesulfonamide in 4.0 mL of ethyl acetate and 2.0 mL of methanol was added 42 mg of 10% palladium-carbon, and under a hydrogen atmosphere, Stir at room temperature for 1 hour. To the reaction mixture, 10% palladium-carbon (85 mg) was added, and the mixture was stirred at room temperature for 1 hour in a hydrogen atmosphere. To the reaction mixture, 10% palladium-carbon (85 mg) was added, and the mixture was stirred at room temperature for 2 hours under a hydrogen atmosphere. The insoluble material in the reaction mixture was removed by filtration, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 100-50% hexane / ethyl acetate] to give N- (2-amino-5-methoxy-4-phenylphenyl) -N-methyl as a yellow solid. 0.11 g of methanesulfonamide was obtained.
1 H-NMR (CDCl 3 ) δ value: 3.03 (3H, s), 3.28 (3H, s), 3.69 (3H, s), 3.92-4.00 (2H, broad), 6.77 (1H, s), 6.80 ( 1H, s), 7.30-7.36 (1H, m), 7.37-7.43 (2H, m), 7.45-7.50 (2H, m).
参考例２３
1H-NMR(DMSO-d6)δ値：3.04(3H,s),3.05(3H,s),5.40-5.46(2H,broad),6.68(1H,dd,J=8.3,2.1Hz),6.92(1H,d,J=2.1Hz),7.13(1H,d,J=8.3Hz).Reference Example 23
1 H-NMR (DMSO-d 6 ) δ value: 3.04 (3H, s), 3.05 (3H, s), 5.40-5.46 (2H, broad), 6.68 (1H, dd, J = 8.3, 2.1 Hz), 6.92 (1H, d, J = 2.1Hz), 7.13 (1H, d, J = 8.3Hz).
参考例２４
1H-NMR(DMSO-d6)δ値：3.08(3H,s),3.11(3H,s),5.19-5.26(2H,broad),6.84(1H,dd,J=8.0,2.0Hz),7.02(1H,d,J=2.0Hz),7.28(1H,d,J=8.0Hz),7.33-7.38(1H,m),7.42-7.58(4H,m).Reference Example 24
1 H-NMR (DMSO-d 6 ) δ value: 3.08 (3H, s), 3.11 (3H, s), 5.19-5.26 (2H, broad), 6.84 (1H, dd, J = 8.0, 2.0 Hz), 7.02 (1H, d, J = 2.0Hz), 7.28 (1H, d, J = 8.0Hz), 7.33-7.38 (1H, m), 7.42-7.58 (4H, m).
参考例２５
1H-NMR(CDCl3)δ値：3.09(3H,s),3.28(3H,s),4.20-4.28(2H,broad),5.87(1H,s),6.50(1H,d,J=1.8Hz),6.57(1H,d,J=1.8Hz),7.32-7.44(3H,m),7.47-7.53(2H,m).Reference Example 25
1 H-NMR (CDCl 3 ) δ value: 3.09 (3H, s), 3.28 (3H, s), 4.20-4.28 (2H, broad), 5.87 (1H, s), 6.50 (1H, d, J = 1.8 Hz), 6.57 (1H, d, J = 1.8Hz), 7.32-7.44 (3H, m), 7.47-7.53 (2H, m).
参考例２６
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.12(3H,s),5.06-5.12(2H,broad),6.86(1H,d,J=8.0Hz),7.26(1H,d,J=11.5Hz),7.37-7.42(1H,m),7.44-7.50(4H,m).Reference Example 26
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.12 (3H, s), 5.06-5.12 (2H, broad), 6.86 (1H, d, J = 8.0 Hz), 7.26 ( 1H, d, J = 11.5Hz), 7.37-7.42 (1H, m), 7.44-7.50 (4H, m).
参考例２７
Ｎ−（２−アミノ−４−（（Ｅ）−２−フェニルビニル）フェニル）−Ｎ−メチルメタンスルホンアミド
1H-NMR(CDCl3)δ値：2.98(3H,s),3.24(3H,s),4.18-4.31(2H,broad),6.90-7.14(5H,m),7.23-7.30(1H,m),7.33-7.39(2H,m),7.46-7.52(2H,m).Reference Example 27
N- (2-amino-4-((E) -2-phenylvinyl) phenyl) -N-methylmethanesulfonamide
1 H-NMR (CDCl 3 ) δ value: 2.98 (3H, s), 3.24 (3H, s), 4.18-4.31 (2H, broad), 6.90-7.14 (5H, m), 7.23-7.30 (1H, m ), 7.33-7.39 (2H, m), 7.46-7.52 (2H, m).
参考例２８
Ｎ−（（３−アミノ−５−フェニル）ピリジン−２−イル）−Ｎ−メチルメタンスルホンアミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.18(3H,s),5.40-5.45(2H,broad),7.37(1H,d,J=2.3Hz),7.38-7.44(1H,m),7.46-7.52(2H,m),7.59-7.64(2H,m),7.96(1H,d,J=2.3Hz).Reference Example 28
N-((3-amino-5-phenyl) pyridin-2-yl) -N-methylmethanesulfonamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.18 (3H, s), 5.40-5.45 (2H, broad), 7.37 (1H, d, J = 2.3 Hz), 7.38- 7.44 (1H, m), 7.46-7.52 (2H, m), 7.59-7.64 (2H, m), 7.96 (1H, d, J = 2.3Hz).
参考例２９
1H-NMR(CDCl3)δ値：2.79-2.92(4H,m),2.95(3H,s),3.22(3H,s),4.13-4.20(2H,broad),6.59(1H,dd,J=8.0,2.0Hz),6.65(1H,d,J=2.0Hz),7.03(1H,d,J=8.0Hz),7.17-7.23(3H,m),7.24-7.32(2H,m).Reference Example 29
1 H-NMR (CDCl 3 ) δ value: 2.79-2.92 (4H, m), 2.95 (3H, s), 3.22 (3H, s), 4.13-4.20 (2H, broad), 6.59 (1H, dd, J = 8.0,2.0Hz), 6.65 (1H, d, J = 2.0Hz), 7.03 (1H, d, J = 8.0Hz), 7.17-7.23 (3H, m), 7.24-7.32 (2H, m).
参考例３０
Ｎ−（２−アミノ−４−（１Ｈ−ピロール−１−イル）フェニル）−Ｎ−メチルメタンスルホンアミド
1H-NMR(DMSO-d6)δ値：3.06(3H,s),3.09(3H,s),5.30-5.36(2H,broad),6.24(2H,t,J=2.0Hz),6.72(1H,dd,J=8.5,2.6Hz),6.87(1H,d,J=2.6Hz),7.19(2H,t,J=2.0Hz),7.26(1H,d,J=8.5Hz).Reference Example 30
N- (2-amino-4- (1H-pyrrol-1-yl) phenyl) -N-methylmethanesulfonamide
1 H-NMR (DMSO-d 6 ) δ value: 3.06 (3H, s), 3.09 (3H, s), 5.30-5.36 (2H, broad), 6.24 (2H, t, J = 2.0 Hz), 6.72 ( 1H, dd, J = 8.5,2.6Hz), 6.87 (1H, d, J = 2.6Hz), 7.19 (2H, t, J = 2.0Hz), 7.26 (1H, d, J = 8.5Hz).
参考例３１
1H-NMR(DMSO-d6)δ値：2.75(3H,d,J=5.1Hz),4.53-4.59(2H,broad),4.72-4.78(1H,m),6.45(1H,d,J=8.1Hz),6.83-6.90(2H,m),7.17-7.22(1H,m),7.32-7.38(2H,m),7.46-7.52(2H,m).Reference Example 31
1 H-NMR (DMSO-d 6 ) δ value: 2.75 (3H, d, J = 5.1 Hz), 4.53-4.59 (2H, broad), 4.72-4.78 (1H, m), 6.45 (1H, d, J = 8.1Hz), 6.83-6.90 (2H, m), 7.17-7.22 (1H, m), 7.32-7.38 (2H, m), 7.46-7.52 (2H, m).
参考例３２
1H-NMR(DMSO-d6)δ値：2.25(3H,s),2.61(3H,s),4.70-5.14(2H,broad),6.69(1H,s),6.79-6.83(1H,m),7.24-7.30(1H,m),7.36-7.43(2H,m),7.47-7.54(2H,m).Reference Example 32
1 H-NMR (DMSO-d 6 ) δ value: 2.25 (3H, s), 2.61 (3H, s), 4.70-5.14 (2H, broad), 6.69 (1H, s), 6.79-6.83 (1H, m ), 7.24-7.30 (1H, m), 7.36-7.43 (2H, m), 7.47-7.54 (2H, m).
参考例３３
1H-NMR(DMSO-d6)δ値：3.08(3H,s),3.20(3H,s),7.48(1H,dd,J=8.5,2.2Hz),7.54-7.67(4H,m),7.86-7.93(2H,m),8.33(1H,d,J=2.2Hz),9.59(1H,s).Reference Example 33
1 H-NMR (DMSO-d 6 ) δ value: 3.08 (3H, s), 3.20 (3H, s), 7.48 (1H, dd, J = 8.5, 2.2 Hz), 7.54-7.67 (4H, m), 7.86-7.93 (2H, m), 8.33 (1H, d, J = 2.2Hz), 9.59 (1H, s).
参考例３４
1H-NMR(DMSO-d6)δ値：7.50(1H,dd,J=8.9,2.3Hz),7.56-7.70(3H,m),7.94-7.98(2H,m),8.01(1H,d,J=2.3Hz),8.09(1H,d,J=8.9Hz),10.85(1H,s).Reference Example 34
1 H-NMR (DMSO-d 6 ) δ value: 7.50 (1H, dd, J = 8.9, 2.3 Hz), 7.56-7.70 (3H, m), 7.94-7.98 (2H, m), 8.01 (1H, d , J = 2.3Hz), 8.09 (1H, d, J = 8.9Hz), 10.85 (1H, s).
参考例３５
1H-NMR(DMSO-d6)δ値：2.41(3H,s),7.55-7.68(3H,m),7.92-7.99(3H,m),8.10(1H,s),10.75(1H,s).Reference Example 35
1 H-NMR (DMSO-d 6 ) δ value: 2.41 (3H, s), 7.55-7.68 (3H, m), 7.92-7.99 (3H, m), 8.10 (1H, s), 10.75 (1H, s ).
参考例３６
1H-NMR(CDCl3)δ値：3.89(3H,s),7.50-7.66(4H,m),7.70(1H,d,J=9.0Hz),7.93-7.98(2H,m),8.56(1H,s).Reference Example 36
1 H-NMR (CDCl 3 ) δ value: 3.89 (3H, s), 7.50-7.66 (4H, m), 7.70 (1H, d, J = 9.0 Hz), 7.93-7.98 (2H, m), 8.56 ( 1H, s).
参考例３７
1H-NMR(DMSO-d6)δ値：2.77(3H,d,J=5.1Hz),5.32-5.39(1H,m),6.73(1H,d,J=8.6Hz),7.21-7.27(1H,m),7.36-7.62(9H,m),8.00-8.06(2H,m),9.68(1H,s).Reference Example 37
1 H-NMR (DMSO-d 6 ) δ value: 2.77 (3H, d, J = 5.1 Hz), 5.32-5.39 (1H, m), 6.73 (1H, d, J = 8.6 Hz), 7.21-7.27 ( 1H, m), 7.36-7.62 (9H, m), 8.00-8.06 (2H, m), 9.68 (1H, s).
参考例３８
Ｎ−（３−メチル−２−（メチルアミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.32(3H,s),2.74(3H,d,J=5.8Hz),4.36(1H,q,J=5.8Hz),7.26-7.34(2H,m),7.38-7.44(2H,m),7.52-7.63(6H,m),7.97-8.03(2H,m),9.81(1H,s).Reference Example 38
N- (3-Methyl-2- (methylamino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.32 (3H, s), 2.74 (3H, d, J = 5.8 Hz), 4.36 (1H, q, J = 5.8 Hz), 7.26-7.34 (2H, m), 7.38-7.44 (2H, m), 7.52-7.63 (6H, m), 7.97-8.03 (2H, m), 9.81 (1H, s).
参考例３９
1H-NMR(DMSO-d6)δ値：7.46-7.69(6H,m),7.73(1H,dd,J=8.6,2.0Hz),7.74-7.80(2H,m),7.96-8.02(2H,m),8.14(1H,d,J=8.6Hz),8.18(1H,d,J=2.0Hz),10.86(1H,s).Reference Example 39
1 H-NMR (DMSO-d 6 ) δ value: 7.46-7.69 (6H, m), 7.73 (1H, dd, J = 8.6,2.0 Hz), 7.74-7.80 (2H, m), 7.96-8.02 (2H , m), 8.14 (1H, d, J = 8.6Hz), 8.18 (1H, d, J = 2.0Hz), 10.86 (1H, s).
参考例４０
1H-NMR(DMSO-d6)δ値：2.31(3H,s),7.42-7.68(8H,m),7.70(1H,s),7.94-7.97(2H,m),8.01(1H,s),10.72(1H,s).Reference Example 40
1 H-NMR (DMSO-d 6 ) δ value: 2.31 (3H, s), 7.42-7.68 (8H, m), 7.70 (1H, s), 7.94-7.97 (2H, m), 8.01 (1H, s ), 10.72 (1H, s).
参考例４１
1H-NMR(CDCl3)δ値：3.41(3H,s),7.34(1H,d,J=8.6Hz),7.40-7.64(8H,m),7.85(1H,d,J=8.6Hz),7.96-8.01(2H,m),8.67(1H,s).Reference Example 41
1 H-NMR (CDCl 3 ) δ value: 3.41 (3H, s), 7.34 (1H, d, J = 8.6Hz), 7.40-7.64 (8H, m), 7.85 (1H, d, J = 8.6Hz) , 7.96-8.01 (2H, m), 8.67 (1H, s).
参考例４２
1H-NMR(DMSO-d6)δ値：5.07-5.14(2H,broad),6.88(1H,d,J=8.3Hz),7.22-7.28(1H,m),7.34(1H,dd,J=8.3,2.2Hz),7.30-7.43(2H,m),7.50-7.63(6H,m),7.98-8.06(2H,m),9.75(1H,s).Reference Example 42
1 H-NMR (DMSO-d 6 ) δ value: 5.07-5.14 (2H, broad), 6.88 (1H, d, J = 8.3 Hz), 7.22-7.28 (1H, m), 7.34 (1H, dd, J = 8.3,2.2Hz), 7.30-7.43 (2H, m), 7.50-7.63 (6H, m), 7.98-8.06 (2H, m), 9.75 (1H, s).
参考例４３
1H-NMR(DMSO-d6)δ値：2.16(3H,s),4.92-4.98(2H,broad),6.71(1H,s),7.07(1H,s),7.26-7.33(3H,m),7.36-7.43(2H,m),7.48-7.60(3H,m),7.94-8.02(2H,m),9.67(1H,s).Reference Example 43
1 H-NMR (DMSO-d 6 ) δ value: 2.16 (3H, s), 4.92-4.98 (2H, broad), 6.71 (1H, s), 7.07 (1H, s), 7.26-7.33 (3H, m ), 7.36-7.43 (2H, m), 7.48-7.60 (3H, m), 7.94-8.02 (2H, m), 9.67 (1H, s).
参考例４４
1H-NMR(CDCl3)δ値：3.39(3H,s),4.37(2H,s),6.69(1H,d,J=8.4Hz),7.12(1H,d,J=8.4Hz),7.27-7.33(1H,m),7.37-7.43(2H,m),7.49-7.62(5H,m),7.94-8.00(2H,m),8.21(1H,s).Reference Example 44
1 H-NMR (CDCl 3 ) δ value: 3.39 (3H, s), 4.37 (2H, s), 6.69 (1H, d, J = 8.4 Hz), 7.12 (1H, d, J = 8.4 Hz), 7.27 -7.33 (1H, m), 7.37-7.43 (2H, m), 7.49-7.62 (5H, m), 7.94-8.00 (2H, m), 8.21 (1H, s).
参考例４５
1H-NMR(DMSO-d6)δ値：7.42-7.47(1H,m),7.49-7.55(2H,m),7.70(1H,dd,J=11.1,8.8Hz),7.74-7.78(2H,m),8.13(1H,ddd,J=8.8,4.4,2.4Hz),8.36(1H,dd,J=7.1,2.4Hz).Reference Example 45
1 H-NMR (DMSO-d 6 ) δ value: 7.42-7.47 (1H, m), 7.49-7.55 (2H, m), 7.70 (1H, dd, J = 11.1, 8.8Hz), 7.74-7.78 (2H , m), 8.13 (1H, ddd, J = 8.8, 4.4, 2.4Hz), 8.36 (1H, dd, J = 7.1, 2.4Hz).
参考例４６
1H-NMR(DMSO-d6)δ値：1.30(6H,d,J=6.4Hz),3.96-4.06(1H,m),7.21(1H,d,J=9.5Hz),7.31-7.36(1H,m),7.43-7.48(2H,m),7.64-7.68(2H,m),7.89-7.97(2H,m),8.32(1H,d,J=2.4Hz).Reference Example 46
1 H-NMR (DMSO-d 6 ) δ value: 1.30 (6H, d, J = 6.4 Hz), 3.96-4.06 (1H, m), 7.21 (1H, d, J = 9.5 Hz), 7.31-7.36 ( 1H, m), 7.43-7.48 (2H, m), 7.64-7.68 (2H, m), 7.89-7.97 (2H, m), 8.32 (1H, d, J = 2.4Hz).
参考例４７
1H-NMR(CDCl3)δ値：0.67-0.73(2H,m),0.91-0.98(2H,m),2.60-2.68(1H,m),7.30-7.37(1H,m),7.39-7.47(3H,m),7.54-7.60(2H,m),7.76(1H,dd,J=8.9,2.3Hz),8.08-8.15(1H,broad),8.42(1H,d,J=2.3Hz).Reference Example 47
1 H-NMR (CDCl 3 ) δ value: 0.67-0.73 (2H, m), 0.91-0.98 (2H, m), 2.60-2.68 (1H, m), 7.30-7.37 (1H, m), 7.39-7.47 (3H, m), 7.54-7.60 (2H, m), 7.76 (1H, dd, J = 8.9,2.3Hz), 8.08-8.15 (1H, broad), 8.42 (1H, d, J = 2.3Hz).
参考例４８
1H-NMR(CDCl3)δ値：1.41(3H,t,J=7.2Hz),3.41(2H,qd,J=7.2,5.1Hz),6.95(1H,d,J=9.0Hz),7.30-7.36(1H,m),7.40-7.46(2H,m),7.54-7.59(2H,m),7.73(1H,dd,J=9.0,2.3Hz),7.99-8.06(1H,broad),8.45(1H,d,J=2.3Hz).Reference Example 48
1 H-NMR (CDCl 3 ) δ value: 1.41 (3H, t, J = 7.2 Hz), 3.41 (2H, qd, J = 7.2, 5.1 Hz), 6.95 (1H, d, J = 9.0 Hz), 7.30 -7.36 (1H, m), 7.40-7.46 (2H, m), 7.54-7.59 (2H, m), 7.73 (1H, dd, J = 9.0,2.3Hz), 7.99-8.06 (1H, broad), 8.45 (1H, d, J = 2.3Hz).
参考例４９
1H-NMR(DMSO-d6)δ値：1.18(6H,d,J=6.4Hz),3.63-3.73(1H,m),4.79(1H,d,J=7.6Hz),6.82(1H,d,J=8.6Hz),7.21-7.27(1H,m),7.36-7.47(3H,m),7.50-7.62(6H,m),7.97-8.05(2H,m),9.70(1H,s).Reference Example 49
1 H-NMR (DMSO-d 6 ) δ value: 1.18 (6H, d, J = 6.4 Hz), 3.63-3.73 (1H, m), 4.79 (1H, d, J = 7.6 Hz), 6.82 (1H, d, J = 8.6Hz), 7.21-7.27 (1H, m), 7.36-7.47 (3H, m), 7.50-7.62 (6H, m), 7.97-8.05 (2H, m), 9.70 (1H, s) .
参考例５０
Ｎ−（２−シクロプロピルアミノ−５−フェニルフェニル）ベンズアミド
1H-NMR(CDCl3)δ値：0.51-0.58(2H,m),0.75-0.82(2H,m),2.51-2.59(1H,m),4.78(1H,s),7.24-7.33(2H,m),(7.36-7.43(2H,m),7.46-7.68(8H,m),7.89-7.97(2H,m).Reference Example 50
N- (2-cyclopropylamino-5-phenylphenyl) benzamide
1 H-NMR (CDCl 3 ) δ value: 0.51-0.58 (2H, m), 0.75-0.82 (2H, m), 2.51-2.59 (1H, m), 4.78 (1H, s), 7.24-7.33 (2H , m), (7.36-7.43 (2H, m), 7.46-7.68 (8H, m), 7.89-7.97 (2H, m).
参考例５１
Ｎ−（２−エチルアミノ−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：1.20(3H,t,J=7.1Hz),3.12-3.21(2H,m),5.14(1H,t,J=5.4Hz),6.79(1H,d,J=8.5Hz),7.24(1H,t,J=7.3Hz),7.36-7.43(2H,m),7.45(1H,dd,J=8.5,2.1Hz),7.50-7.62(6H,m),7.99-8.05(2H,m),9.70(1H,s).Reference Example 51
N- (2-ethylamino-5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 1.20 (3H, t, J = 7.1 Hz), 3.12-3.21 (2H, m), 5.14 (1H, t, J = 5.4 Hz), 6.79 (1H, d, J = 8.5Hz), 7.24 (1H, t, J = 7.3Hz), 7.36-7.43 (2H, m), 7.45 (1H, dd, J = 8.5,2.1Hz), 7.50-7.62 (6H, m ), 7.99-8.05 (2H, m), 9.70 (1H, s).
参考例５２
1H-NMR(DMSO-d6)δ値：3.18(2H,t,J=8.4Hz),3.81(2H,t,J=8.4Hz),7.28-7.34(1H,m),7.40-7.47(2H,m),7.59-7.68(3H,m),7.87-7.90(1H,m),8.07(1H,s).Reference Example 52
1 H-NMR (DMSO-d 6 ) δ value: 3.18 (2H, t, J = 8.4 Hz), 3.81 (2H, t, J = 8.4 Hz), 7.28-7.34 (1H, m), 7.40-7.47 ( 2H, m), 7.59-7.68 (3H, m), 7.87-7.90 (1H, m), 8.07 (1H, s).
参考例５３
1H-NMR(DMSO-d6)δ値：3.17(3H,s),3.24(2H,t,J=7.8Hz),4.22(2H,t,J=7.8Hz),7.40-7.45(1H,m),7.47-7.54(2H,m),7.72-7.76(2H,m),7.96-8.03(2H,m).Reference Example 53
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 3.24 (2H, t, J = 7.8 Hz), 4.22 (2H, t, J = 7.8 Hz), 7.40-7.45 (1H, m), 7.47-7.54 (2H, m), 7.72-7.76 (2H, m), 7.96-8.03 (2H, m).
参考例５４
１−（エチルスルホニル）−７−ニトロ−５−フェニルインドリン
1H-NMR(DMSO-d6)δ値：1.28(3H,t,J=7.3Hz),3.24(2H,t,J=7.8Hz),3.38(2H,q,J=7.3Hz),4.22(2H,t,J=7.8Hz),7.40-7.45(1H,m),7.47-7.53(2H,m),7.72-7.76(2H,m),7.96-8.02(2H,m).Reference Example 54
1- (Ethylsulfonyl) -7-nitro-5-phenylindoline
1 H-NMR (DMSO-d 6 ) δ value: 1.28 (3H, t, J = 7.3Hz), 3.24 (2H, t, J = 7.8Hz), 3.38 (2H, q, J = 7.3Hz), 4.22 (2H, t, J = 7.8Hz), 7.40-7.45 (1H, m), 7.47-7.53 (2H, m), 7.72-7.76 (2H, m), 7.96-8.02 (2H, m).
参考例５５
1H-NMR(DMSO-d6)δ値：2.99(3H,s),3.04(2H,t,J=7.6Hz),4.00(2H,t,J=7.6Hz),5.34-5.39(2H,broad),6.84-6.90(2H,m),7.30-7.36(1H,m),7.40-7.46(2H,m),7.54-7.58(2H,m).Reference Example 55
1 H-NMR (DMSO-d 6 ) δ value: 2.99 (3H, s), 3.04 (2H, t, J = 7.6 Hz), 4.00 (2H, t, J = 7.6 Hz), 5.34-5.39 (2H, broad), 6.84-6.90 (2H, m), 7.30-7.36 (1H, m), 7.40-7.46 (2H, m), 7.54-7.58 (2H, m).
参考例５６
1H-NMR(DMSO-d6)δ値：1.21(3H,t,J=7.3Hz),3.03(2H,t,J=7.5Hz),3.18(2H,q,J=7.3Hz),3.99(2H,t,J=7.5Hz),5.33-5.40(2H,broad),6.84-6.90(2H,m),7.29-7.36(1H,m),7.39-7.46(2H,m),7.52-7.58(2H,m).Reference Example 56
1 H-NMR (DMSO-d 6 ) δ value: 1.21 (3H, t, J = 7.3 Hz), 3.03 (2H, t, J = 7.5 Hz), 3.18 (2H, q, J = 7.3 Hz), 3.99 (2H, t, J = 7.5Hz), 5.33-5.40 (2H, broad), 6.84-6.90 (2H, m), 7.29-7.36 (1H, m), 7.39-7.46 (2H, m), 7.52-7.58 (2H, m).
参考例５７
1H-NMR(DMSO-d6)δ値：1.85-2.00(2H,m),2.86-2.90(2H,m),3.19(3H,s),3.70-3.74(2H,m),7.76(1H,s),8.19(1H,s).Reference Example 57
1 H-NMR (DMSO-d 6 ) δ value: 1.85-2.00 (2H, m), 2.86-2.90 (2H, m), 3.19 (3H, s), 3.70-3.74 (2H, m), 7.76 (1H , s), 8.19 (1H, s).
参考例５８
1H-NMR(DMSO-d6)δ値：1.94-2.01(2H,m),2.88-2.94(2H,m),3.21(3H,s),3.74-3.79(2H,m),7.29-7.34(2H,m),7.38(1H,s),7.39-7.48(3H,m),8.16(1H,s).Reference Example 58
1 H-NMR (DMSO-d 6 ) δ value: 1.94-2.01 (2H, m), 2.88-2.94 (2H, m), 3.21 (3H, s), 3.74-3.79 (2H, m), 7.29-7.34 (2H, m), 7.38 (1H, s), 7.39-7.48 (3H, m), 8.16 (1H, s).
参考例５９
1H-NMR(DMSO-d6)δ値：1.41(9H,s),7.46(1H,d,J=8.4Hz),8.41(1H,d,J=8.4Hz),10.71(1H,s).Reference Example 59
1 H-NMR (DMSO-d 6 ) δ value: 1.41 (9H, s), 7.46 (1H, d, J = 8.4Hz), 8.41 (1H, d, J = 8.4Hz), 10.71 (1H, s) .
参考例６０
1H-NMR(DMSO-d6)δ値：1.44(9H,s),7.52-7.59(3H,m),7.94(1H,d,J=8.5Hz),8.13-8.20(2H,m),8.44(1H,d,J=8.5Hz),10.43(1H,s).Reference Example 60
1 H-NMR (DMSO-d 6 ) δ value: 1.44 (9H, s), 7.52-7.59 (3H, m), 7.94 (1H, d, J = 8.5 Hz), 8.13-8.20 (2H, m), 8.44 (1H, d, J = 8.5Hz), 10.43 (1H, s).
参考例６１
1H-NMR(DMSO-d6)δ値：1.47(9H,s),5.06-5.12(2H,broad),7.16(1H,d,J=8.3Hz),7.25-7.31(1H,m),7.37-7.43(2H,m),7.56(1H,d,J=8.3Hz),7.89-7.94(2H,m),8.95(1H,s).Reference Example 61
1 H-NMR (DMSO-d 6 ) δ value: 1.47 (9H, s), 5.06-5.12 (2H, broad), 7.16 (1H, d, J = 8.3 Hz), 7.25-7.31 (1H, m), 7.37-7.43 (2H, m), 7.56 (1H, d, J = 8.3Hz), 7.89-7.94 (2H, m), 8.95 (1H, s).
参考例６２
1H-NMR(CDCl3)δ値：1.56(9H,s),2.97(3H,s),7.41-7.51(3H,m),7.62(1H,d,J=8.3Hz),7.90-7.95(2H,m),8.00(1H,d,J=8.3Hz).Reference Example 62
1 H-NMR (CDCl 3 ) δ value: 1.56 (9H, s), 2.97 (3H, s), 7.41-7.51 (3H, m), 7.62 (1H, d, J = 8.3 Hz), 7.90-7.95 ( 2H, m), 8.00 (1H, d, J = 8.3Hz).
参考例６３
得られたｔｅｒｔ−ブチル＝（（３−（メチル（メチルスルホニル）アミノ）−６−フェニル）ピリジン−２−イル）カルバマート0.18gのトリフルオロ酢酸3.6mL溶液を、室温で20分間攪拌した。減圧下で溶媒を留去し、飽和炭酸水素ナトリウム水溶液および酢酸エチルを加えた。有機層を分取し、飽和塩化ナトリウム水溶液で洗浄後、無水硫酸マグネシウムで乾燥させ、減圧下で溶媒を留去した。得られた残留物にジイソプロピルエーテルを加え、固形物をろ取し、白色固体のＮ−（（２−アミノ−６−フェニル）ピリジン−３−イル）−Ｎ−メチルメタンスルホンアミド0.10gを得た。
1H-NMR(CDCl3)δ値：3.00(3H,s),3.26(3H,s),5.00-5.13(2H,broad),7.13(1H,d,J=8.1Hz),7.37-7.53(4H,m),7.90-7.95(2H,m).Reference Example 63
The obtained tert-butyl = ((3- (methyl (methylsulfonyl) amino) -6-phenyl) pyridin-2-yl) carbamate 0.18 g in trifluoroacetic acid 3.6 mL solution was stirred at room temperature for 20 minutes. The solvent was distilled off under reduced pressure, and a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate were added. The organic layer was separated, washed with a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Diisopropyl ether was added to the obtained residue, and the solid was collected by filtration to obtain 0.10 g of N-((2-amino-6-phenyl) pyridin-3-yl) -N-methylmethanesulfonamide as a white solid. It was.
1 H-NMR (CDCl 3 ) δ value: 3.00 (3H, s), 3.26 (3H, s), 5.00-5.13 (2H, broad), 7.13 (1H, d, J = 8.1 Hz), 7.37-7.53 ( 4H, m), 7.90-7.95 (2H, m).
参考例６４
1H-NMR(DMSO-d6)δ値：3.08(3H,s),3.31(3H,s),7.32-7.40(2H,m),7.82-7.89(2H,m),7.89(1H,d,J=8.5Hz),8.06(1H,dd,J=8.5,2.4Hz),8.21(1H,d,J=2.4Hz).Reference Example 64
1 H-NMR (DMSO-d 6 ) δ value: 3.08 (3H, s), 3.31 (3H, s), 7.32-7.40 (2H, m), 7.82-7.89 (2H, m), 7.89 (1H, d , J = 8.5Hz), 8.06 (1H, dd, J = 8.5,2.4Hz), 8.21 (1H, d, J = 2.4Hz).
参考例６５〜６７
参考例６４と同様にして、表８に示す化合物を得た。Reference Examples 65-67
In the same manner as in Reference Example 64, the compounds shown in Table 8 were obtained.
Ｎ−（４−（２，４−ジフルオロフェニル）−２−ニトロフェニル）−Ｎ−メチルメタンスルホンアミド
1H-NMR(CDCl3)δ値：3.05(3H,s),3.35(3H,s),6.94-7.06(2H,m),7.44(1H,ddd,J=8.7,8.7,6.3Hz),7.65(1H,d,J=8.6Hz),7.78(1H,ddd,J=8.3,1.8,1.8Hz),8.03-8.06(1H,m).N- (4- (2,4-difluorophenyl) -2-nitrophenyl) -N-methylmethanesulfonamide
1 H-NMR (CDCl 3 ) δ value: 3.05 (3H, s), 3.35 (3H, s), 6.94-7.06 (2H, m), 7.44 (1H, ddd, J = 8.7, 8.7, 6.3 Hz), 7.65 (1H, d, J = 8.6Hz), 7.78 (1H, ddd, J = 8.3,1.8,1.8Hz), 8.03-8.06 (1H, m).
Ｎ−メチル−Ｎ−（４−（４−メチルフェニル）−２−ニトロフェニル）メタンスルホンアミド
1H-NMR(CDCl3)δ値：2.42(3H,s),3.04(3H,s),3.34(3H,s),7.30(2H,d,J=8.1Hz),7.49(2H,d,J=8.1Hz),7.61(1H，d，J=8.5Hz),7.82(1H,dd,J=8.5,2.3Hz),8.08(1H,d,J=2.3Hz).N-methyl-N- (4- (4-methylphenyl) -2-nitrophenyl) methanesulfonamide
1 H-NMR (CDCl 3 ) δ value: 2.42 (3H, s), 3.04 (3H, s), 3.34 (3H, s), 7.30 (2H, d, J = 8.1 Hz), 7.49 (2H, d, J = 8.1Hz), 7.61 (1H, d, J = 8.5Hz), 7.82 (1H, dd, J = 8.5, 2.3Hz), 8.08 (1H, d, J = 2.3Hz).
Ｎ−メチル−Ｎ−（２−ニトロ−４−（ピリジン−３−イル）フェニル）メタンスルホンアミド
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.33(3H,s),7.55(1H,dd,J=7.9,4.5Hz),7.95(1H,d,J=8.3Hz),8.17(1H,dd,J=8.3,1.9Hz),8.22(1H,d,J=7.9Hz),8.32(1H,d,J=2.1Hz),8.66(1H,d,J=4.5Hz),9.01(1H,d,J=2.1Hz).N-methyl-N- (2-nitro-4- (pyridin-3-yl) phenyl) methanesulfonamide
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.33 (3H, s), 7.55 (1H, dd, J = 7.9, 4.5 Hz), 7.95 (1H, d, J = 8.3 Hz), 8.17 (1H, dd, J = 8.3,1.9Hz), 8.22 (1H, d, J = 7.9Hz), 8.32 (1H, d, J = 2.1Hz), 8.66 (1H, d, J = 4.5 Hz), 9.01 (1H, d, J = 2.1Hz).
参考例６８
1H-NMR(DMSO-d6)δ値：3.08(3H,s),3.30(3H,s),3.82(3H,s),7.05-7.10(2H,m),7.73-7.78(2H,m),7.84(1H,d,J=8.4Hz),8.03(1H,dd,J=8.4,2.4Hz),8.16(1H,d,J=2.4Hz).Reference Example 68
1 H-NMR (DMSO-d 6 ) δ value: 3.08 (3H, s), 3.30 (3H, s), 3.82 (3H, s), 7.05-7.10 (2H, m), 7.73-7.78 (2H, m ), 7.84 (1H, d, J = 8.4Hz), 8.03 (1H, dd, J = 8.4, 2.4Hz), 8.16 (1H, d, J = 2.4Hz).
参考例６９
1H-NMR(DMSO-d6)δ値：1.42(9H,s),3.09(3H,s),3.24(3H,s),3.31(3H,s),7.41-7.46(2H,m),7.74-7.80(2H,m),7.88(1H,d,J=8.6Hz),8.07(1H,dd,J=8.6,2.2Hz),8.21(1H,d,J=2.2Hz).Reference Example 69
1 H-NMR (DMSO-d 6 ) δ value: 1.42 (9H, s), 3.09 (3H, s), 3.24 (3H, s), 3.31 (3H, s), 7.41-7.46 (2H, m), 7.74-7.80 (2H, m), 7.88 (1H, d, J = 8.6Hz), 8.07 (1H, dd, J = 8.6,2.2Hz), 8.21 (1H, d, J = 2.2Hz).
参考例７０
Ｎ−（４−（２−フルオロ−４−メチルフェニル）−２−ニトロフェニル）−Ｎ−メチルメタンスルホンアミド
1H-NMR(CDCl3)δ値：2.42(3H,s),3.04(3H,s),3.35(3H,s),7.00-7.10(2H,m),7.33(1H,dd,J=8.1,8.1Hz),7.62(1H,d,J=8.5Hz),7.80(1H,ddd,J=8.3,1.8,1.8Hz),8.06-8.09(1H,m).Reference Example 70
N- (4- (2-Fluoro-4-methylphenyl) -2-nitrophenyl) -N-methylmethanesulfonamide
1 H-NMR (CDCl 3 ) δ value: 2.42 (3H, s), 3.04 (3H, s), 3.35 (3H, s), 7.00-7.10 (2H, m), 7.33 (1H, dd, J = 8.1 8.1Hz), 7.62 (1H, d, J = 8.5Hz), 7.80 (1H, ddd, J = 8.3,1.8,1.8Hz), 8.06-8.09 (1H, m).
参考例７１
Ｎ−（４−（２−ヒドロキシフェニル）−２−ニトロフェニル）−Ｎ−メチルメタンスルホンアミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.32(3H,s),6.93(1H,dd,J=7.4,7.4Hz),7.00(1H,d,J=8.3Hz),7.22-7.30(1H,m),7.39(1H,dd,J=7.7,1.3Hz),7.82(1H,d,J=8.3Hz),7.94(1H,dd,J=8.3,2.2Hz),8.12(1H,d,J=2.2Hz),9.96(1H,s).Reference Example 71
N- (4- (2-hydroxyphenyl) -2-nitrophenyl) -N-methylmethanesulfonamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.32 (3H, s), 6.93 (1H, dd, J = 7.4, 7.4 Hz), 7.00 (1H, d, J = 8.3 Hz), 7.22-7.30 (1H, m), 7.39 (1H, dd, J = 7.7,1.3Hz), 7.82 (1H, d, J = 8.3Hz), 7.94 (1H, dd, J = 8.3,2.2Hz) ), 8.12 (1H, d, J = 2.2Hz), 9.96 (1H, s).
参考例７２
1H-NMR(CDCl3)δ値：2.18(3H,s),3.05(3H,s),3.34(3H,s),7.18-7.23(1H,m),7.34-7.52(3H,m),7.62(1H,d,J=8.3Hz),7.70(1H,dd,J=8.3,2.0Hz),8.01(1H,d,J=2.0Hz).Reference Example 72
1 H-NMR (CDCl 3 ) δ value: 2.18 (3H, s), 3.05 (3H, s), 3.34 (3H, s), 7.18-7.23 (1H, m), 7.34-7.52 (3H, m), 7.62 (1H, d, J = 8.3Hz), 7.70 (1H, dd, J = 8.3,2.0Hz), 8.01 (1H, d, J = 2.0Hz).
参考例７３
1H-NMR(DMSO-d6)δ値：1.41(9H,s),3.07(3H,s),3.11(3H,s),3.22(3H,s),5.20-5.26(2H,broad),6.83(1H,dd,J=8.2,2.0Hz),7.02(1H,d,J=2.0Hz),7.27(1H,d,J=8.2Hz),7.32-7.38(2H,m),7.50-7.55(2H,m).Reference Example 73
1 H-NMR (DMSO-d 6 ) δ value: 1.41 (9H, s), 3.07 (3H, s), 3.11 (3H, s), 3.22 (3H, s), 5.20-5.26 (2H, broad), 6.83 (1H, dd, J = 8.2,2.0Hz), 7.02 (1H, d, J = 2.0Hz), 7.27 (1H, d, J = 8.2Hz), 7.32-7.38 (2H, m), 7.50-7.55 (2H, m).
参考例７４〜７８
参考例７３と同様にして、表９に示す化合物を得た。Reference examples 74-78
In the same manner as in Reference Example 73, the compounds shown in Table 9 were obtained.
Ｎ−（２−アミノ−４−（４−フルオロフェニル）フェニル）−Ｎ−メチルメタンスルホンアミド
1H-NMR(DMSO-d6)δ値：3.07(3H,s),3.11(3H,s),5.20-5.28(2H,broad),6.81(1H,dd,J=8.1,2.1Hz),6.99(1H,d,J=2.1Hz),7.24-7.31(3H,m),7.56-7.63(2H,m).N- (2-amino-4- (4-fluorophenyl) phenyl) -N-methylmethanesulfonamide
1 H-NMR (DMSO-d 6 ) δ value: 3.07 (3H, s), 3.11 (3H, s), 5.20-5.28 (2H, broad), 6.81 (1H, dd, J = 8.1, 2.1 Hz), 6.99 (1H, d, J = 2.1Hz), 7.24-7.31 (3H, m), 7.56-7.63 (2H, m).
Ｎ−（２−アミノ−４−（２，４−ジフルオロフェニル）フェニル）−Ｎ−メチルメタンスルホンアミド
1H-NMR(DMSO-d6)δ値：3.08(3H,s),3.11(3H,s),5.24-5.31(2H,broad),6.66-6.73(1H,m),6.88-6.93(1H,m),7.14-7.21(1H,m),7.29(1H,d,J=8.0Hz),7.30-7.38(1H,m),7.48-7.56(1H,m).N- (2-amino-4- (2,4-difluorophenyl) phenyl) -N-methylmethanesulfonamide
1 H-NMR (DMSO-d 6 ) δ value: 3.08 (3H, s), 3.11 (3H, s), 5.24-5.31 (2H, broad), 6.66-6.73 (1H, m), 6.88-6.93 (1H , m), 7.14-7.21 (1H, m), 7.29 (1H, d, J = 8.0Hz), 7.30-7.38 (1H, m), 7.48-7.56 (1H, m).
Ｎ−（２−アミノ−４−（２−フルオロ−４−メチルフェニル）フェニル）−Ｎ−メチルメタンスルホンアミド
1H-NMR(DMSO-d6)δ値：2.35(3H,s),3.08(3H,s),3.11(3H,s),5.20-5.27(2H,broad),6.70(1H,ddd,J=8.1,8.1,1.8Hz),6.91(1H,dd,J=1.7,1.7Hz),7.06-7.15(2H,m),7.27(1H,d,J=8.3Hz),7.34(1H,dd,J=8.2,8.2Hz).N- (2-amino-4- (2-fluoro-4-methylphenyl) phenyl) -N-methylmethanesulfonamide
1 H-NMR (DMSO-d 6 ) δ value: 2.35 (3H, s), 3.08 (3H, s), 3.11 (3H, s), 5.20-5.27 (2H, broad), 6.70 (1H, ddd, J = 8.1, 8.1, 1.8Hz), 6.91 (1H, dd, J = 1.7,1.7Hz), 7.06-7.15 (2H, m), 7.27 (1H, d, J = 8.3Hz), 7.34 (1H, dd, J = 8.2,8.2Hz).
Ｎ−（２−アミノ−４−（ピリジン−３−イル）フェニル）−Ｎ−メチルメタンスルホンアミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.13(3H,s),5.27-5.35(2H,broad),6.90(1H,dd,J=8.3,2.2Hz),7.07(1H,d,J=2.2Hz),7.33(1H,d,J=8.3Hz),7.47(1H,dd,J=7.9,4.8Hz),7.96(1H,ddd,J=8.0,8.0,1.9Hz),8.57(1H,dd,J=4.9,1.5Hz),8.80(1H,d,J=2.0Hz).N- (2-amino-4- (pyridin-3-yl) phenyl) -N-methylmethanesulfonamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.13 (3H, s), 5.27-5.35 (2H, broad), 6.90 (1H, dd, J = 8.3, 2.2 Hz), 7.07 (1H, d, J = 2.2Hz), 7.33 (1H, d, J = 8.3Hz), 7.47 (1H, dd, J = 7.9,4.8Hz), 7.96 (1H, ddd, J = 8.0,8.0, 1.9Hz), 8.57 (1H, dd, J = 4.9,1.5Hz), 8.80 (1H, d, J = 2.0Hz).
Ｎ−（２−アミノ−４−（４−メトキシフェニル）フェニル）−Ｎ−メチルメタンスルホンアミド
1H-NMR(DMSO-d6)δ値：3.07(3H,s),3.10(3H,s),3.79(3H,s),5.15-5.23(2H,broad),6.79(1H,dd,J=8.3,2.1Hz),6.96-7.04(3H,m),7.24(1H,d,J=8.3Hz),7.47-7.54(2H,m).N- (2-amino-4- (4-methoxyphenyl) phenyl) -N-methylmethanesulfonamide
1 H-NMR (DMSO-d 6 ) δ value: 3.07 (3H, s), 3.10 (3H, s), 3.79 (3H, s), 5.15-5.23 (2H, broad), 6.79 (1H, dd, J = 8.3, 2.1Hz), 6.96-7.04 (3H, m), 7.24 (1H, d, J = 8.3Hz), 7.47-7.54 (2H, m).
参考例７９
1H-NMR(CDCl3)δ値：2.39(3H,s),3.00(3H,s),3.27(3H,s),6.95(1H,dd,J=8.1,2.0Hz),6.99(1H,d,J=2.0Hz),7.17(1H,d,J=8.1Hz),7.23(2H,d,J=8.2Hz),7.43(2H,d,J=8.2Hz).Reference Example 79
1 H-NMR (CDCl 3 ) δ value: 2.39 (3H, s), 3.00 (3H, s), 3.27 (3H, s), 6.95 (1H, dd, J = 8.1, 2.0 Hz), 6.99 (1H, d, J = 2.0 Hz), 7.17 (1 H, d, J = 8.1 Hz), 7.23 (2 H, d, J = 8.2 Hz), 7.43 (2 H, d, J = 8.2 Hz).
参考例８０
1H-NMR(DMSO-d6)δ値：2.13(3H,s),3.07(3H,s),3.11(3H,s),5.22-5.29(2H,broad),6.58(1H,dd,J=8.1,2.1Hz),6.80(1H,d,J=2.1Hz),7.16-7.21(1H,m),7.25(1H,d,J=8.1Hz),7.31-7.44(3H,m).
参考例８１
Ｎ−（５−ブロモ−２−（メチル（メチルスルホニル）アミノ）フェニル）−２−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.15(3H,s),3.25(3H,s),4.09(3H,s),7.14-7.20(1H,m),7.29(1H,d,J=7.8Hz),7.41(1H,dd,J=8.5,2.4Hz),7.60-7.66(2H,m),8.12(1H,dd,J=7.9,1.8Hz),8.82(1H,d,J=2.4Hz),10.84(1H,s).Reference Example 80
1 H-NMR (DMSO-d 6 ) δ value: 2.13 (3H, s), 3.07 (3H, s), 3.11 (3H, s), 5.22-5.29 (2H, broad), 6.58 (1H, dd, J = 8.1, 2.1Hz), 6.80 (1H, d, J = 2.1Hz), 7.16-7.21 (1H, m), 7.25 (1H, d, J = 8.1Hz), 7.31-7.44 (3H, m).
Reference Example 81
N- (5-bromo-2- (methyl (methylsulfonyl) amino) phenyl) -2-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.15 (3H, s), 3.25 (3H, s), 4.09 (3H, s), 7.14-7.20 (1H, m), 7.29 (1H, d, J = 7.8Hz), 7.41 (1H, dd, J = 8.5,2.4Hz), 7.60-7.66 (2H, m), 8.12 (1H, dd, J = 7.9,1.8Hz), 8.82 (1H, d, J = 2.4Hz), 10.84 (1H, s).
参考例８２
1H-NMR(DMSO-d6)δ値：1.32(12H,s),3.07(3H,s),3.22(3H,s),7.54-7.67(5H,m),7.88-7.93(2H,m),8.34-8.38(1H,m),9.56(1H,s).Reference Example 82
1 H-NMR (DMSO-d 6 ) δ value: 1.32 (12H, s), 3.07 (3H, s), 3.22 (3H, s), 7.54-7.67 (5H, m), 7.88-7.93 (2H, m ), 8.34-8.38 (1H, m), 9.56 (1H, s).
参考例８３
２−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：1.32(12H,s),3.14(3H,s),3.25(3H,s),4.09(3H,s),7.16(1H,dd,J=7.6,7.6Hz),7.28(1H,d,J=8.3Hz),7.49(1H,dd,J=7.9,1.4Hz),7.58-7.65(1H,m),7.66(1H,d,J=7.8Hz),8.12(1H,dd,J=7.8,1.7Hz),8.89(1H,d,J=1.2Hz),10.75(1H,s).Reference Example 83
2-Methoxy-N- (2- (methyl (methylsulfonyl) amino) -5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 1.32 (12H, s), 3.14 (3H, s), 3.25 (3H, s), 4.09 (3H, s), 7.16 (1H, dd, J = 7.6 , 7.6Hz), 7.28 (1H, d, J = 8.3Hz), 7.49 (1H, dd, J = 7.9,1.4Hz), 7.58-7.65 (1H, m), 7.66 (1H, d, J = 7.8Hz ), 8.12 (1H, dd, J = 7.8,1.7Hz), 8.89 (1H, d, J = 1.2Hz), 10.75 (1H, s).
参考例８４
1H-NMR(CDCl3)δ値：5.16(2H,s),6.15(1H,s),6.17-6.25(2H,broad),7.34-7.48(5H,m),8.58(1H,s).Reference Example 84
1 H-NMR (CDCl 3 ) δ value: 5.16 (2H, s), 6.15 (1H, s), 6.17-6.25 (2H, broad), 7.34-7.48 (5H, m), 8.58 (1H, s).
参考例８５
1H-NMR(DMSO-d6)δ値：1.48(9H,s),5.28(2H,s),7.34-7.40(1H,m),7.40-7.46(2H,m),7.51-7.56(2H,m),7.71(1H,s),8.43(1H,s),9.77(1H,s).Reference Example 85
1 H-NMR (DMSO-d 6 ) δ value: 1.48 (9H, s), 5.28 (2H, s), 7.34-7.40 (1H, m), 7.40-7.46 (2H, m), 7.51-7.56 (2H , m), 7.71 (1H, s), 8.43 (1H, s), 9.77 (1H, s).
参考例８６
1H-NMR(DMSO-d6)δ値：1.50(9H,s),5.25(2H,s),7.30-7.46(8H,m),7.54-7.60(2H,m),7.87(1H,s),8.01(1H,s),9.83(1H,s).Reference Example 86
1 H-NMR (DMSO-d 6 ) δ value: 1.50 (9H, s), 5.25 (2H, s), 7.30-7.46 (8H, m), 7.54-7.60 (2H, m), 7.87 (1H, s ), 8.01 (1H, s), 9.83 (1H, s).
参考例８７
1H-NMR(DMSO-d6)δ値：1.48(9H,s),4.58-4.64(2H,broad),4.88(2H,s),6.72(1H,s),7.22-7.40(9H,m),7.45-7.49(2H,m),8.37-8.41(1H,broad).Reference Example 87
1 H-NMR (DMSO-d 6 ) δ value: 1.48 (9H, s), 4.58-4.64 (2H, broad), 4.88 (2H, s), 6.72 (1H, s), 7.22-7.40 (9H, m ), 7.45-7.49 (2H, m), 8.37-8.41 (1H, broad).
参考例８８
1H-NMR(DMSO-d6)δ値：1.47(9H,s),5.11(2H,s),7.28-7.64(15H,m),7.96(1H,s),7.97(1H,s),8.75(1H,s),9.81(1H,s).Reference Example 88
1 H-NMR (DMSO-d 6 ) δ value: 1.47 (9H, s), 5.11 (2H, s), 7.28-7.64 (15H, m), 7.96 (1H, s), 7.97 (1H, s), 8.75 (1H, s), 9.81 (1H, s).
参考例８９
1H-NMR(DMSO-d6)δ値：5.06(2H,s),5.07-5.12(2H,broad),6.63(1H,s),7.14(1H,s),7.19-7.24(1H,m),7.28-7.42(7H,m),7.47-7.60(5H,m),7.96-8.02(2H,m),9.62(1H,s).Reference Example 89
1 H-NMR (DMSO-d 6 ) δ value: 5.06 (2H, s), 5.07-5.12 (2H, broad), 6.63 (1H, s), 7.14 (1H, s), 7.19-7.24 (1H, m ), 7.28-7.42 (7H, m), 7.47-7.60 (5H, m), 7.96-8.02 (2H, m), 9.62 (1H, s).
参考例９０
1H-NMR(CDCl3)δ値：1.13(3H,t,J=7.1Hz),1.43(9H,s),3.65(2H,q,J=7.1Hz),7.04-7.10(2H,m),7.42-7.47(2H,m).Reference Example 90
1 H-NMR (CDCl 3 ) δ value: 1.13 (3H, t, J = 7.1 Hz), 1.43 (9H, s), 3.65 (2H, q, J = 7.1 Hz), 7.04-7.10 (2H, m) , 7.42-7.47 (2H, m).
参考例９１
1H-NMR(DMSO-d6)δ値：1.05(3H,t,J=7.1Hz),1.29(12H,s),1.38(9H,s),3.62(2H,q,J=7.1Hz),7.24(2H,d,J=8.3Hz),7.64(2H,d,J=8.3Hz).Reference Example 91
1 H-NMR (DMSO-d 6 ) δ value: 1.05 (3H, t, J = 7.1 Hz), 1.29 (12H, s), 1.38 (9H, s), 3.62 (2H, q, J = 7.1 Hz) , 7.24 (2H, d, J = 8.3Hz), 7.64 (2H, d, J = 8.3Hz).
実施例１
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.26(3H,s),7.40-7.45(1H,m),7.49-7.76(9H,m),7.91-7.96(2H,m),8.37(1H,d,J=2.0Hz),9.60(1H,s).Example 1
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.26 (3H, s), 7.40-7.45 (1H, m), 7.49-7.76 (9H, m), 7.91-7.96 (2H) , m), 8.37 (1H, d, J = 2.0Hz), 9.60 (1H, s).
実施例２
Ｎ−（２−（メチル（チオフェン−２−スルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.22(3H,s),6.83(1H,d,J=8.5Hz),7.30(1H,dd,J=5.0,3.8Hz),7.38-7.46(2H,m),7.47-7.53(2H,m),7.56-7.70(6H,m),7.94-7.99(2H,m),8.10(1H,dd,J=5.0,1.3Hz),8.34(1H,d,J=2.2Hz),9.74(1H,s).Example 2
N- (2- (methyl (thiophen-2-sulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.22 (3H, s), 6.83 (1H, d, J = 8.5 Hz), 7.30 (1H, dd, J = 5.0, 3.8 Hz), 7.38-7.46 ( 2H, m), 7.47-7.53 (2H, m), 7.56-7.70 (6H, m), 7.94-7.99 (2H, m), 8.10 (1H, dd, J = 5.0,1.3Hz), 8.34 (1H, d, J = 2.2Hz), 9.74 (1H, s).
実施例３
1H-NMR(DMSO-d6)δ値：2.43(3H,s),3.16(3H,s),3.17(3H,s),7.38-7.43(1H,m),7.46-7.72(8H,m),7.86(1H,d,J=2.0Hz),7.97-8.03(2H,m),9.66(1H,s).Example 3
1 H-NMR (DMSO-d 6 ) δ value: 2.43 (3H, s), 3.16 (3H, s), 3.17 (3H, s), 7.38-7.43 (1H, m), 7.46-7.72 (8H, m ), 7.86 (1H, d, J = 2.0Hz), 7.97-8.03 (2H, m), 9.66 (1H, s).
実施例４
1H-NMR(DMSO-d6)δ値：3.50(3H,s),7.40-7.74(10H,m),7.84-7.88(1H,m),7.92-7.98(2H,m),10.25(1H,s).Example 4
1 H-NMR (DMSO-d 6 ) δ value: 3.50 (3H, s), 7.40-7.74 (10H, m), 7.84-7.88 (1H, m), 7.92-7.98 (2H, m), 10.25 (1H , s).
実施例５
1H-NMR(DMSO-d6)δ値：1.01(3H,t,J=7.1Hz),3.16(3H,s),3.60-3.80(2H,m),7.40-7.46(1H,m),7.49-7.55(2H,m),7.57-7.69(4H,m),7.69-7.74(3H,m),7.88-7.93(2H,m),8.54(1H,d,J=2.0Hz),9.30(1H,s).Example 5
1 H-NMR (DMSO-d 6 ) δ value: 1.01 (3H, t, J = 7.1 Hz), 3.16 (3H, s), 3.60-3.80 (2H, m), 7.40-7.46 (1H, m), 7.49-7.55 (2H, m), 7.57-7.69 (4H, m), 7.69-7.74 (3H, m), 7.88-7.93 (2H, m), 8.54 (1H, d, J = 2.0Hz), 9.30 ( 1H, s).
実施例６
1H-NMR(CDCl3)δ値：0.37-0.47(1H,m),0.60-0.70(1H,m),0.97-1.18(2H,m),3.00-3.05(1H,m),3.11(3H,s),7.35-7.60(8H,m),7.63-7.70(2H,m),7.93-7.99(2H,m),8.67-8.70(1H,m),9.04(1H,s).Example 6
1 H-NMR (CDCl 3 ) δ value: 0.37-0.47 (1H, m), 0.60-0.70 (1H, m), 0.97-1.18 (2H, m), 3.00-3.05 (1H, m), 3.11 (3H , s), 7.35-7.60 (8H, m), 7.63-7.70 (2H, m), 7.93-7.99 (2H, m), 8.67-8.70 (1H, m), 9.04 (1H, s).
実施例７
1H-NMR(DMSO-d6)δ値：1.20(3H,t,J=7.3Hz),3.11(2H,q,J=7.3Hz),7.36-7.42(1H,m),7.46-7.70(9H,m),7.97-8.06(3H,m),9.22(1H,s),9.93(1H,s).Example 7
1 H-NMR (DMSO-d 6 ) δ value: 1.20 (3H, t, J = 7.3 Hz), 3.11 (2H, q, J = 7.3 Hz), 7.36-7.42 (1H, m), 7.46-7.70 ( 9H, m), 7.97-8.06 (3H, m), 9.22 (1H, s), 9.93 (1H, s).
実施例８〜１２
実施例７と同様にして、表１０に示す化合物を得た。Examples 8-12
In the same manner as in Example 7, the compounds shown in Table 10 were obtained.
Ｎ−（２−（（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.03(3H,s),7.36-7.42(1H,m),7.46-7.71(9H,m),7.97-8.02(2H,m),8.06-8.11(1H,m),9.23(1H,s),9.88(1H,s).N- (2-((methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.03 (3H, s), 7.36-7.42 (1H, m), 7.46-7.71 (9H, m), 7.97-8.02 (2H, m), 8.06-8.11 (1H, m), 9.23 (1H, s), 9.88 (1H, s).
Ｎ−（２−（（シクロプロピルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：0.83-0.94(4H,m),2.56-2.64(1H,m),7.37-7.42(1H,m),7.47-7.71(9H,m),7.98-8.03(2H,m),8.14(1H,d,J=2.0Hz),9.25(1H,s),9.90(1H,s).N- (2-((cyclopropylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 0.83-0.94 (4H, m), 2.56-2.64 (1H, m), 7.37-7.42 (1H, m), 7.47-7.71 (9H, m), 7.98 -8.03 (2H, m), 8.14 (1H, d, J = 2.0Hz), 9.25 (1H, s), 9.90 (1H, s).
Ｎ−（２−（（イソプロピルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：1.23(6H,d,J=6.8Hz),3.20-3.34(1H,m),7.36-7.42(1H,m),7.45-7.52(2H,m),7.54-7.70(7H,m),7.98-8.04(3H,m),9.16(1H,s),9.98(1H,s).N- (2-((isopropylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 1.23 (6H, d, J = 6.8 Hz), 3.20-3.34 (1H, m), 7.36-7.42 (1H, m), 7.45-7.52 (2H, m ), 7.54-7.70 (7H, m), 7.98-8.04 (3H, m), 9.16 (1H, s), 9.98 (1H, s).
Ｎ−（２−（（フェニルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：7.19(1H,d,J=8.3Hz),7.34-7.41(1H,m),7.42-7.50(5H,m),7.55-7.70(8H,m),7.83-7.88(2H,m),8.06(1H,d,J=2.0Hz),9.64(1H,s),9.79(1H,s).N- (2-((phenylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 7.19 (1H, d, J = 8.3 Hz), 7.34-7.41 (1H, m), 7.42-7.50 (5H, m), 7.55-7.70 (8H, m ), 7.83-7.88 (2H, m), 8.06 (1H, d, J = 2.0Hz), 9.64 (1H, s), 9.79 (1H, s).
Ｎ−（２−（（ベンジルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：4.52(2H,s),7.28-7.42(6H,m),7.46-7.52(2H,m),7.53-7.71(7H,m),7.94-8.00(2H,m),8.06(1H,s),9.25(1H,s),9.85(1H,s).N- (2-((benzylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 4.52 (2H, s), 7.28-7.42 (6H, m), 7.46-7.52 (2H, m), 7.53-7.71 (7H, m), 7.94-8.00 (2H, m), 8.06 (1H, s), 9.25 (1H, s), 9.85 (1H, s).
実施例１３
Ｎ−（４−メチル−２−（（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.25(3H,s),3.03(3H,s),7.35-7.50(6H,m),7.54-7.65(4H,m),7.93-7.98(2H,m),9.15(1H,s),9.81(1H,s).Example 13
N- (4-Methyl-2-((methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.25 (3H, s), 3.03 (3H, s), 7.35-7.50 (6H, m), 7.54-7.65 (4H, m), 7.93-7.98 (2H , m), 9.15 (1H, s), 9.81 (1H, s).
実施例１４
Ｎ−（２−メトキシ−６−（（メチルスルホニル）アミノ）−３−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.00(3H,s),3.34(3H,s),7.31-7.40(3H,m),7.42-7.49(2H,m),7.51-7.64(5H,m),8.01-8.07(2H,m),8.99(1H,s),9.61(1H,s).Example 14
N- (2-methoxy-6-((methylsulfonyl) amino) -3-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.00 (3H, s), 3.34 (3H, s), 7.31-7.40 (3H, m), 7.42-7.49 (2H, m), 7.51-7.64 (5H , m), 8.01-8.07 (2H, m), 8.99 (1H, s), 9.61 (1H, s).
実施例１５
1H-NMR(DMSO-d6)δ値：7.34-7.53(5H,m),7.55-7.69(5H,m),7.93-7.99(2H,m),8.14-8.23(1H,m),9.94(1H,s).Example 15
1 H-NMR (DMSO-d 6 ) δ value: 7.34 to 7.53 (5H, m), 7.55 to 7.69 (5H, m), 7.93 to 7.99 (2H, m), 8.14 to 8.23 (1H, m), 9.94 (1H, s).
実施例１６
1H-NMR(CDCl3)δ値：1.50(3H,t,J=7.5Hz),3.21(2H,q,J=7.5Hz),3.34(3H,s),7.35-7.69(10H,m),7.98-8.05(2H,m),8.70(1H,d,J=2.0Hz),9.36(1H,s).Example 16
1 H-NMR (CDCl 3 ) δ value: 1.50 (3H, t, J = 7.5 Hz), 3.21 (2H, q, J = 7.5 Hz), 3.34 (3H, s), 7.35-7.69 (10H, m) 7.98-8.05 (2H, m), 8.70 (1H, d, J = 2.0Hz), 9.36 (1H, s).
実施例１７
Ｎ−（２−（（シクロプロピルスルホニル）（メチル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：0.85-1.10(4H,m),2.83-2.92(1H,m),3.29(3H,s),7.39-7.45(1H,m),7.49-7.66(6H,m),7.67-7.73(2H,m),7.77(1H,d,J=8.3Hz),7.90-7.96(2H,m),8.38(1H,d,J=2.0Hz),9.57(1H,s).Example 17
N- (2-((cyclopropylsulfonyl) (methyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 0.85-1.10 (4H, m), 2.83-2.92 (1H, m), 3.29 (3H, s), 7.39-7.45 (1H, m), 7.49-7.66 (6H, m), 7.67-7.73 (2H, m), 7.77 (1H, d, J = 8.3Hz), 7.90-7.96 (2H, m), 8.38 (1H, d, J = 2.0Hz), 9.57 ( 1H, s).
実施例１８
Ｎ−（４−メチル−２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.26(3H,s),3.12(3H,s),3.25(3H,s),7.37-7.44(3H,m),7.46-7.52(2H,m),7.53-7.64(4H,m),7.87-7.94(3H,m),9.50(1H,s).Example 18
N- (4-Methyl-2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.26 (3H, s), 3.12 (3H, s), 3.25 (3H, s), 7.37-7.44 (3H, m), 7.46-7.52 (2H, m ), 7.53-7.64 (4H, m), 7.87-7.94 (3H, m), 9.50 (1H, s).
実施例１９
Ｎ−（２−メトキシ−６−（メチル（メチルスルホニル）アミノ）−３−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.04(3H,s),3.16(3H,s),3.35(3H,s),7.38-7.43(3H,m),7.45-7.63(7H,m),7.97-8.02(2H,m),9.77(1H,s).Example 19
N- (2-methoxy-6- (methyl (methylsulfonyl) amino) -3-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.04 (3H, s), 3.16 (3H, s), 3.35 (3H, s), 7.38-7.43 (3H, m), 7.45-7.63 (7H, m ), 7.97-8.02 (2H, m), 9.77 (1H, s).
実施例２０
1H-NMR(DMSO-d6)δ値：1.30(6H,d,J=6.8Hz),3.29(3H,s),3.52-3.63(1H,m),7.39-7.46(1H,m),7.48-7.74(9H,m),7.94-8.00(2H,m),8.23-8.26(1H,m),9.62(1H,s).Example 20
1 H-NMR (DMSO-d 6 ) δ value: 1.30 (6H, d, J = 6.8 Hz), 3.29 (3H, s), 3.52-3.63 (1H, m), 7.39-7.46 (1H, m), 7.48-7.74 (9H, m), 7.94-8.00 (2H, m), 8.23-8.26 (1H, m), 9.62 (1H, s).
実施例２１、２２
実施例２０と同様にして、表１１に示す化合物を得た。Examples 21 and 22
In the same manner as in Example 20, the compounds shown in Table 11 were obtained.
Ｎ−（２−（（ベンゼンスルホニル）（メチル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.17(3H,s),6.73(1H,d,J=8.3Hz),7.37-7.44(2H,m),7.47-7.53(2H,m),7.57-7.71(9H,m),7.73-7.79(1H,m),7.95-8.00(2H,m),8.36(1H,d,J=2.0Hz),9.72(1H,s).N- (2-((benzenesulfonyl) (methyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 6.73 (1H, d, J = 8.3 Hz), 7.37-7.44 (2H, m), 7.47-7.53 (2H, m), 7.57-7.71 (9H, m), 7.73-7.79 (1H, m), 7.95-8.00 (2H, m), 8.36 (1H, d, J = 2.0Hz), 9.72 (1H, s).
Ｎ−（２−（（ベンジルスルホニル）（メチル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.30(3H,s),4.64(2H,s),7.34-7.46(6H,m),7.49-7.64(7H,m),7.67-7.73(2H,m),7.90-7.96(2H,m),8.32(1H,s),9.61(1H,s).N- (2-((benzylsulfonyl) (methyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.30 (3H, s), 4.64 (2H, s), 7.34-7.46 (6H, m), 7.49-7.64 (7H, m), 7.67-7.73 (2H , m), 7.90-7.96 (2H, m), 8.32 (1H, s), 9.61 (1H, s).
実施例２３
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),7.55-7.67(6H,m),7.70-7.76(3H,m),7.90-7.96(2H,m),8.37(1H,d,J=2.2Hz),9.62(1H,s).Example 23
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 7.55-7.67 (6H, m), 7.70-7.76 (3H, m), 7.90-7.96 (2H , m), 8.37 (1H, d, J = 2.2Hz), 9.62 (1H, s).
実施例２４〜４４
実施例２３と同様にして、表１２に示す化合物を得た。Examples 24-44
In the same manner as in Example 23, the compounds shown in Table 12 were obtained.
Ｎ−（５−（２−クロロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.13(3H,s),3.27(3H,s),7.36(1H,dd,J=8.2,2.0Hz),7.42-7.50(3H,m),7.54-7.66(4H,m),7.74(1H,d,J=8.3Hz),7.88-7.94(2H,m),8.20(1H,d,J=2.0Hz),9.59(1H,s).N- (5- (2-chlorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.13 (3H, s), 3.27 (3H, s), 7.36 (1H, dd, J = 8.2, 2.0 Hz), 7.42-7.50 (3H, m), 7.54-7.66 (4H, m), 7.74 (1H, d, J = 8.3Hz), 7.88-7.94 (2H, m), 8.20 (1H, d, J = 2.0Hz), 9.59 (1H, s).
Ｎ−（５−（３−クロロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.26(3H,s),7.46-7.51(1H,m),7.52-7.70(6H,m),7.72-7.77(2H,m),7.91-7.96(2H,m),8.38(1H,d,J=2.2Hz),9.62(1H,s).N- (5- (3-chlorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.26 (3H, s), 7.46-7.51 (1H, m), 7.52-7.70 (6H, m), 7.72-7.77 (2H , m), 7.91-7.96 (2H, m), 8.38 (1H, d, J = 2.2Hz), 9.62 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（チオフェン−３−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.24(3H,s),7.54-7.71(7H,m),7.91-7.96(3H,m),8.34(1H,d,J=2.0Hz),9.59(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (thiophen-3-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.24 (3H, s), 7.54-7.71 (7H, m), 7.91-7.96 (3H, m), 8.34 (1H, d , J = 2.0Hz), 9.59 (1H, s).
Ｎ−（５−（３−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.26(3H,s),7.22-7.30(1H,m),7.51-7.67(7H,m),7.75(1H,d,J=8.6Hz),7.91-7.97(2H,m),8.36-8.41(1H,m),9.63(1H,s).N- (5- (3-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.26 (3H, s), 7.22-7.30 (1H, m), 7.51-7.67 (7H, m), 7.75 (1H, d , J = 8.6Hz), 7.91-7.97 (2H, m), 8.36-8.41 (1H, m), 9.63 (1H, s).
Ｎ−（５−（４−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),7.31-7.38(2H,m),7.54-7.67(4H,m),7.70-7.77(3H,m),7.91-7.96(2H,m),8.35(1H,d,J=2.2Hz),9.61(1H,s).N- (5- (4-Fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 7.31-7.38 (2H, m), 7.54-7.67 (4H, m), 7.70-7.77 (3H , m), 7.91-7.96 (2H, m), 8.35 (1H, d, J = 2.2Hz), 9.61 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（２−メチルフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.31(3H,s),3.13(3H,s),3.27(3H,s),7.24-7.36(5H,m),7.54-7.66(3H.m),7.70(1H,d,J=8.0Hz),7.88-7.94(2H,m),8.09(1H,d,J=1.7Hz),9.57(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (2-methylphenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.31 (3H, s), 3.13 (3H, s), 3.27 (3H, s), 7.24-7.36 (5H, m), 7.54-7.66 (3H.m ), 7.70 (1H, d, J = 8.0Hz), 7.88-7.94 (2H, m), 8.09 (1H, d, J = 1.7Hz), 9.57 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（３−メチルフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.40(3H,s),3.11(3H,s),3.26(3H,s),7.23(1H,d,J=7.3Hz),7.39(1H,t,J=7.6Hz),7.45-7.52(2H,m),7.53-7.67(4H,m),7.72(1H,d,J=8.3Hz),7.91-7.96(2H,m),8.35(1H,d,J=2.2Hz),9.59(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (3-methylphenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.40 (3H, s), 3.11 (3H, s), 3.26 (3H, s), 7.23 (1H, d, J = 7.3 Hz), 7.39 (1H, t, J = 7.6Hz), 7.45-7.52 (2H, m), 7.53-7.67 (4H, m), 7.72 (1H, d, J = 8.3Hz), 7.91-7.96 (2H, m), 8.35 (1H , d, J = 2.2 Hz), 9.59 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−メチルフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.36(3H,s),3.11(3H,s),3.25(3H,s),7.29-7.35(2H,m),7.52-7.66(6H,m),7.70(1H,d,J=8.3Hz),7.90-7.96(2H,m),8.35(1H,d,J=2.0Hz),9.58(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (4-methylphenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.36 (3H, s), 3.11 (3H, s), 3.25 (3H, s), 7.29-7.35 (2H, m), 7.52-7.66 (6H, m ), 7.70 (1H, d, J = 8.3Hz), 7.90-7.96 (2H, m), 8.35 (1H, d, J = 2.0Hz), 9.58 (1H, s).
Ｎ−（５−（２，３−ジフルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.13(3H,s),3.27(3H,s),7.31-7.44(2H,m),7.46-7.67(5H,m),7.78(1H,d,J=8.3Hz),7.89-7.96(2H,m),8.30(1H,s),9.64(1H,s).N- (5- (2,3-difluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.13 (3H, s), 3.27 (3H, s), 7.31-7.44 (2H, m), 7.46-7.67 (5H, m), 7.78 (1H, d , J = 8.3Hz), 7.89-7.96 (2H, m), 8.30 (1H, s), 9.64 (1H, s).
Ｎ−（５−（２，４−ジフルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.26(3H,s),7.24(1H,td,J=8.5,2.4Hz),7.38-7.47(2H,m),7.54-7.68(4H,m),7.75(1H,d,J=8.3Hz),7.89-7.95(2H,m),8.26(1H,s),9.62(1H,s).N- (5- (2,4-difluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.26 (3H, s), 7.24 (1H, td, J = 8.5, 2.4 Hz), 7.38-7.47 (2H, m), 7.54-7.68 (4H, m), 7.75 (1H, d, J = 8.3Hz), 7.89-7.95 (2H, m), 8.26 (1H, s), 9.62 (1H, s).
Ｎ−（５−（２−メトキシフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),3.80(3H,s),7.06(1H,t,J=7.5Hz),7.15(1H,d,J=8.3Hz),7.31-7.42(3H,m),7.54-7.67(4H,m),7.89-7.94(2H,m),8.19(1H,d,J=2.0Hz),9.54(1H,s).N- (5- (2-methoxyphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 3.80 (3H, s), 7.06 (1H, t, J = 7.5 Hz), 7.15 (1H, d, J = 8.3Hz), 7.31-7.42 (3H, m), 7.54-7.67 (4H, m), 7.89-7.94 (2H, m), 8.19 (1H, d, J = 2.0Hz), 9.54 (1H , s).
Ｎ−（５−（３−メトキシフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),3.84(3H,s),6.99(1H,dd,J=8.1,2.6Hz),7.18-7.22(1H,m),7.23-7.27(1H,m),7.43(1H,t,J=7.9Hz),7.55-7.66(4H,m),7.72(1H,d,J=8.3Hz),7.91-7.96(2H,m),8.34(1H,d,J=2.0Hz),9.60(1H,s).N- (5- (3-methoxyphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 3.84 (3H, s), 6.99 (1H, dd, J = 8.1, 2.6 Hz), 7.18- 7.22 (1H, m), 7.23-7.27 (1H, m), 7.43 (1H, t, J = 7.9Hz), 7.55-7.66 (4H, m), 7.72 (1H, d, J = 8.3Hz), 7.91 -7.96 (2H, m), 8.34 (1H, d, J = 2.0Hz), 9.60 (1H, s).
Ｎ−（５−（４−メトキシフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.25(3H,s),3.82(3H,s),7.04-7.10(2H,m),7.52(1H,dd,J=8.3,2.1Hz),7.55-7.70(6H,m),7.90-7.96(2H,m),8.32(1H,d,J=2.1Hz),9.57(1H,s).N- (5- (4-methoxyphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.25 (3H, s), 3.82 (3H, s), 7.04-7.10 (2H, m), 7.52 (1H, dd, J = 8.3, 2.1Hz), 7.55-7.70 (6H, m), 7.90-7.96 (2H, m), 8.32 (1H, d, J = 2.1Hz), 9.57 (1H, s).
Ｎ−（５−（フラン−２−イル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.23(3H,s),6.64(1H,dd,J=3.4,2.0Hz),7.03(1H,d,J=3.4Hz),7.55-7.70(5H,m),7.80-7.83(1H,m),7.90-7.95(2H,m),8.41(1H,d,J=1.9Hz),9.58(1H,s).N- (5- (furan-2-yl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.23 (3H, s), 6.64 (1H, dd, J = 3.4, 2.0 Hz), 7.03 (1H, d, J = 3.4 Hz), 7.55-7.70 (5H, m), 7.80-7.83 (1H, m), 7.90-7.95 (2H, m), 8.41 (1H, d, J = 1.9Hz), 9.58 (1H, s).
Ｎ−（５−（フラン−３−イル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.08(3H,s),3.22(3H,s),6.95-6.98(1H,m),7.51-7.66(5H,m),7.77-7.80(1H,m),7.90-7.95(2H,m),8.20(1H,d,J=2.0Hz),8.23-8.26(1H,m),9.59(1H,s).N- (5- (furan-3-yl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.08 (3H, s), 3.22 (3H, s), 6.95-6.98 (1H, m), 7.51-7.66 (5H, m), 7.77-7.80 (1H , m), 7.90-7.95 (2H, m), 8.20 (1H, d, J = 2.0Hz), 8.23-8.26 (1H, m), 9.59 (1H, s).
Ｎ−（５−（４−（ヒドロキシメチル）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.26(3H,s),4.56(2H,d,J=5.7Hz),5.25(1H,t,J=5.7Hz),7.42-7.48(2H,m),7.55-7.69(6H,m),7.71(1H,d,J=8.3Hz),7.91-7.96(2H,m),8.37(1H,d,J=2.2Hz),9.60(1H,s).N- (5- (4- (hydroxymethyl) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.26 (3H, s), 4.56 (2H, d, J = 5.7 Hz), 5.25 (1H, t, J = 5.7 Hz) , 7.42-7.48 (2H, m), 7.55-7.69 (6H, m), 7.71 (1H, d, J = 8.3Hz), 7.91-7.96 (2H, m), 8.37 (1H, d, J = 2.2Hz ), 9.60 (1H, s).
Ｎ−（５−（ベンゾ［１，３］ジオキソール−５−イル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.24(3H,s),6.09(2H,s),7.04(1H,d,J=8.1Hz),7.18(1H,dd,J=8.1,1.7Hz),7.27(1H,d,J=1.7Hz),7.51(1H,dd,J=8.3,2.1Hz),7.54-7.70(4H,m),7.89-7.96(2H,m),8.29(1H,d,J=2.1Hz),9.57(1H,s).N- (5- (Benzo [1,3] dioxol-5-yl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.24 (3H, s), 6.09 (2H, s), 7.04 (1H, d, J = 8.1 Hz), 7.18 (1H, dd, J = 8.1,1.7Hz), 7.27 (1H, d, J = 1.7Hz), 7.51 (1H, dd, J = 8.3,2.1Hz), 7.54-7.70 (4H, m), 7.89-7.96 (2H , m), 8.29 (1H, d, J = 2.1Hz), 9.57 (1H, s).
Ｎ−（５−（２，３−ジヒドロベンゾ［１，４］ジオキシン−６−イル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.24(3H,s),4.30(4H,s),6.98(1H,d,J=8.0Hz),7.13-7.20(2H,m),7.50(1H,dd,J=8.4,2.1Hz),7.54-7.69(4H,m),7.89-7.96(2H,m),8.30(1H,d,J=2.1Hz),9.56(1H,s).N- (5- (2,3-dihydrobenzo [1,4] dioxin-6-yl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.24 (3H, s), 4.30 (4H, s), 6.98 (1H, d, J = 8.0 Hz), 7.13-7.20 ( 2H, m), 7.50 (1H, dd, J = 8.4,2.1Hz), 7.54-7.69 (4H, m), 7.89-7.96 (2H, m), 8.30 (1H, d, J = 2.1Hz), 9.56 (1H, s).
Ｎ−（５−（ベンゾフラン−２−イル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.26(3H,s),7.27-7.33(1H,m),7.33-7.40(1H,m),7.53-7.73(6H,m),7.77(1H,d,J=8.5Hz),7.85(1H,dd,J=8.5,2.0Hz),7.93-7.98(2H,m),8.63(1H,d,J=2.1Hz),9.66(1H,s).N- (5- (benzofuran-2-yl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.26 (3H, s), 7.27-7.33 (1H, m), 7.33-7.40 (1H, m), 7.53-7.73 (6H , m), 7.77 (1H, d, J = 8.5Hz), 7.85 (1H, dd, J = 8.5,2.0Hz), 7.93-7.98 (2H, m), 8.63 (1H, d, J = 2.1Hz) , 9.66 (1H, s).
Ｎ−（５−（ベンゾチオフェン−２−イル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.13(3H,s),3.26(3H,s),7.36-7.46(2H,m),7.56-7.68(3H,m),7.69-7.78(2H,m),7.88-7.98(4H,m),8.02(1H,d,J=7.6Hz),8.52-8.56(1H,m),9.64(1H,s).N- (5- (benzothiophen-2-yl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.13 (3H, s), 3.26 (3H, s), 7.36-7.46 (2H, m), 7.56-7.68 (3H, m), 7.69-7.78 (2H , m), 7.88-7.98 (4H, m), 8.02 (1H, d, J = 7.6Hz), 8.52-8.56 (1H, m), 9.64 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（ピリジン−３−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.26(3H,s),7.51-7.68(5H,m),7.78(1H,d,J=8.3Hz),7.91-7.96(2H,m),8.08-8.13(1H,m),8.39(1H,d,J=2.2Hz),8.60-8.65(1H,m),8.92(1H,d,J=2.4Hz),9.65(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (pyridin-3-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.26 (3H, s), 7.51-7.68 (5H, m), 7.78 (1H, d, J = 8.3 Hz), 7.91 7.96 (2H, m), 8.08-8.13 (1H, m), 8.39 (1H, d, J = 2.2Hz), 8.60-8.65 (1H, m), 8.92 (1H, d, J = 2.4Hz), 9.65 (1H, s).
実施例４５
1H-NMR(DMSO-d6)δ値：2.63(3H,s),3.12(3H,s),3.27(3H,s),7.55-7.69(4H,m),7.77(1H,d,J=8.3Hz),7.83-7.89(2H,m),7.91-7.97(2H,m),8.06-8.12(2H,m),8.44(1H,d,J=2.0Hz),9.65(1H,s).Example 45
1 H-NMR (DMSO-d 6 ) δ value: 2.63 (3H, s), 3.12 (3H, s), 3.27 (3H, s), 7.55-7.69 (4H, m), 7.77 (1H, d, J = 8.3Hz), 7.83-7.89 (2H, m), 7.91-7.97 (2H, m), 8.06-8.12 (2H, m), 8.44 (1H, d, J = 2.0Hz), 9.65 (1H, s) .
実施例４６〜５３
実施例４５と同様にして、表１３に示す化合物を得た。Examples 46-53
In the same manner as in Example 45, the compounds shown in Table 13 were obtained.
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（３−ニトロフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.27(3H,s),7.55-7.67(3H,m),7.72(1H,dd,J=8.3,2.2Hz),7.77-7.85(2H,m),7.92-7.97(2H,m),8.16-8.21(1H,m),8.25-8.30(1H,m),8.44-8.49(2H,m),9.68(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (3-nitrophenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.27 (3H, s), 7.55-7.67 (3H, m), 7.72 (1H, dd, J = 8.3, 2.2 Hz), 7.77-7.85 (2H, m), 7.92-7.97 (2H, m), 8.16-8.21 (1H, m), 8.25-8.30 (1H, m), 8.44-8.49 (2H, m), 9.68 (1H, s ).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−ニトロフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.27(3H,s),7.55-7.67(3H,m),7.71(1H,dd,J=8.3,2.1Hz),7.81(1H,d,J=8.3Hz),7.92-7.97(2H,m),7.97-8.03(2H,m),8.33-8.39(2H,m),8.48(1H,d,J=2.1Hz),9.68(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (4-nitrophenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.27 (3H, s), 7.55-7.67 (3H, m), 7.71 (1H, dd, J = 8.3, 2.1 Hz), 7.81 (1H, d, J = 8.3Hz), 7.92-7.97 (2H, m), 7.97-8.03 (2H, m), 8.33-8.39 (2H, m), 8.48 (1H, d, J = 2.1Hz) , 9.68 (1H, s).
Ｎ−（５−（４−（ジメチルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.96(6H,s),3.09(3H,s),3.24(3H,s),6.80-6.86(2H,m),7.49(1H,dd,J=8.3,2.0Hz),7.52-7.66(6H,m),7.90-7.96(2H,m),8.30(1H,d,J=2.0Hz),9.54(1H,s).N- (5- (4- (dimethylamino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.96 (6H, s), 3.09 (3H, s), 3.24 (3H, s), 6.80-6.86 (2H, m), 7.49 (1H, dd, J = 8.3,2.0Hz), 7.52-7.66 (6H, m), 7.90-7.96 (2H, m), 8.30 (1H, d, J = 2.0Hz), 9.54 (1H, s).
Ｎ−（５−（１Ｈ−インドール−５−イル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.26(3H,s),6.51-6.55(1H,m),7.39-7.46(2H,m),7.52(1H,d,J=8.6Hz),7.55-7.71(5H,m),7.85-7.88(1H,m),7.91-7.97(2H,m),8.41(1H,d,J=2.2Hz),9.56(1H,s),11.21(1H,s).N- (5- (1H-Indol-5-yl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.26 (3H, s), 6.51-6.55 (1H, m), 7.39-7.46 (2H, m), 7.52 (1H, d , J = 8.6Hz), 7.55-7.71 (5H, m), 7.85-7.88 (1H, m), 7.91-7.97 (2H, m), 8.41 (1H, d, J = 2.2Hz), 9.56 (1H, s), 11.21 (1H, s).
Ｎ−（５−（１−メチル−１Ｈ−インドール−５−イル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.26(3H,s),3.83(3H,s),6.53(1H,d,J=3.2Hz),7.39(1H,d,J=3.2Hz),7.50(1H,dd,J=8.7,1.6Hz),7.54-7.67(5H,m),7.69(1H,d,J=8.3Hz),7.88(1H,d,J=1.2Hz),7.92-7.97(2H,m),8.42(1H,d,J=2.2Hz),9.58(1H,s).N- (5- (1-Methyl-1H-indol-5-yl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.26 (3H, s), 3.83 (3H, s), 6.53 (1H, d, J = 3.2 Hz), 7.39 (1H, d, J = 3.2Hz), 7.50 (1H, dd, J = 8.7,1.6Hz), 7.54-7.67 (5H, m), 7.69 (1H, d, J = 8.3Hz), 7.88 (1H, d, J = 1.2Hz), 7.92-7.97 (2H, m), 8.42 (1H, d, J = 2.2Hz), 9.58 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（キノリン−６−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.14(3H,s),3.29(3H,s),7.56-7.68(4H,m),7.76(1H,dd,J=8.3,2.0Hz),7.81(1H,d,J=8.3Hz),7.93-7.99(2H,m),8.10-8.18(2H,m),8.32-8.36(1H,m),8.47-8.52(1H,m),8.54(1H,d,J=2.0Hz),8.94(1H,dd,J=4.1,1.5Hz),9.68(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (quinolin-6-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.14 (3H, s), 3.29 (3H, s), 7.56-7.68 (4H, m), 7.76 (1H, dd, J = 8.3, 2.0 Hz), 7.81 (1H, d, J = 8.3Hz), 7.93-7.99 (2H, m), 8.10-8.18 (2H, m), 8.32-8.36 (1H, m), 8.47-8.52 (1H, m), 8.54 ( 1H, d, J = 2.0Hz), 8.94 (1H, dd, J = 4.1,1.5Hz), 9.68 (1H, s).
Ｎ−（５−（２−（（ｔｅｒｔ−ブトキシカルボニル）アミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(CDCl3)δ値：1.49(9H,s),3.05(3H,s),3.35(3H,s),6.59(1H,s),7.12(1H,td,J=7.6,1.0Hz),7.22-7.29(2H,m),7.33-7.42(2H,m),7.49-7.61(3H,m),7.95-8.00(2H,m),8.03-8.10(1H,m),8.48(1H,d,J=2.0Hz),9.29(1H,s).N- (5- (2-((tert-butoxycarbonyl) amino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (CDCl 3 ) δ value: 1.49 (9H, s), 3.05 (3H, s), 3.35 (3H, s), 6.59 (1H, s), 7.12 (1H, td, J = 7.6, 1.0 Hz), 7.22-7.29 (2H, m), 7.33-7.42 (2H, m), 7.49-7.61 (3H, m), 7.95-8.00 (2H, m), 8.03-8.10 (1H, m), 8.48 ( 1H, d, J = 2.0Hz), 9.29 (1H, s).
Ｎ−（５−（４−（（ｔｅｒｔ−ブトキシカルボニル）（メチル）アミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(CDCl3)δ値：1.48(9H,s),3.03(3H,s),3.31(3H,s),3.32(3H,s),7.30-7.37(3H,m),7.40(1H,dd,J=8.3,2.1Hz),7.50-7.63(5H,m),7.97-8.02(2H,m),8.73(1H,d,J=2.1Hz),9.28(1H,s).N- (5- (4-((tert-butoxycarbonyl) (methyl) amino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (CDCl 3 ) δ value: 1.48 (9H, s), 3.03 (3H, s), 3.31 (3H, s), 3.32 (3H, s), 7.30-7.37 (3H, m), 7.40 ( 1H, dd, J = 8.3,2.1Hz), 7.50-7.63 (5H, m), 7.97-8.02 (2H, m), 8.73 (1H, d, J = 2.1Hz), 9.28 (1H, s).
実施例５４
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.26(3H,s),7.55-7.67(3H,m),7.69-7.75(3H,m),7.80(1H,d,J=8.5Hz),7.91-7.97(2H,m),8.47(1H,d,J=2.2Hz),8.67-8.72(2H,m),9.67(1H,s).Example 54
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.26 (3H, s), 7.55-7.67 (3H, m), 7.69-7.75 (3H, m), 7.80 (1H, d , J = 8.5Hz), 7.91-7.97 (2H, m), 8.47 (1H, d, J = 2.2Hz), 8.67-8.72 (2H, m), 9.67 (1H, s).
実施例５５
Ｎ−（５−（２，６−ジフルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.13(3H,s),3.27(3H,s),7.23-7.32(2H,m),7.39(1H,d,J=8.3Hz),7.49-7.66(4H,m),7.77(1H,d,J=8.3Hz),7.89-7.95(2H,m),8.18(1H,s),9.63(1H,s).Example 55
N- (5- (2,6-difluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.13 (3H, s), 3.27 (3H, s), 7.23-7.32 (2H, m), 7.39 (1H, d, J = 8.3 Hz), 7.49- 7.66 (4H, m), 7.77 (1H, d, J = 8.3Hz), 7.89-7.95 (2H, m), 8.18 (1H, s), 9.63 (1H, s).
実施例５６
得られたＮ−（５−（４−（ｔｅｒｔ−ブトキシカルボニル）オキシフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミドにトリフルオロ酢酸5.0mLを加え、室温で2時間30分間攪拌した。減圧下で溶媒を留去し、得られた残留物にジイソプロピルエーテルを加え、固形物をろ取し、白色固体のＮ−（５−（４−ヒドロキシフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド9.0mgを得た。
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.24(3H,s),6.86-6.91(2H,m),7.45-7.67(7H,m),7.90-7.94(2H,m),8.28(1H,d,J=2.0Hz),9.54(1H,s),9.65(1H,s).Example 56
To the obtained N- (5- (4- (tert-butoxycarbonyl) oxyphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide was added 5.0 mL of trifluoroacetic acid, and the mixture was stirred at room temperature for 2 hours and 30 minutes. did. The solvent was distilled off under reduced pressure, diisopropyl ether was added to the resulting residue, the solid was collected by filtration, and white solid N- (5- (4-hydroxyphenyl) -2- (methyl (methylsulfonyl) 9.0 mg of amino) phenyl) benzamide were obtained.
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.24 (3H, s), 6.86-6.91 (2H, m), 7.45-7.67 (7H, m), 7.90-7.94 (2H , m), 8.28 (1H, d, J = 2.0Hz), 9.54 (1H, s), 9.65 (1H, s).
実施例５７、５８
実施例５６と同様にして、表１４に示す化合物を得た。Examples 57, 58
In the same manner as in Example 56, the compounds shown in Table 14 were obtained.
Ｎ−（５−（２−ヒドロキシフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),6.91(1H,td,J=7.4,1.0Hz),6.95-6.99(1H,m),7.17-7.23(1H,m),7.30(1H,dd,J=7.6,1.7Hz),7.45(1H,dd,J=8.3,2.1Hz),7.54-7.66(4H,m),7.89-7.94(2H,m),8.25(1H,d,J=2.1Hz),9.55(1H,s),9.68(1H,s).N- (5- (2-hydroxyphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 6.91 (1H, td, J = 7.4, 1.0 Hz), 6.95-6.99 (1H, m), 7.17-7.23 (1H, m), 7.30 (1H, dd, J = 7.6,1.7Hz), 7.45 (1H, dd, J = 8.3,2.1Hz), 7.54-7.66 (4H, m), 7.89-7.94 ( 2H, m), 8.25 (1H, d, J = 2.1Hz), 9.55 (1H, s), 9.68 (1H, s).
Ｎ−（５−（３−ヒドロキシフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),6.78-6.84(1H,m),7.05-7.13(2H,m),7.30(1H,t,J=7.8Hz),7.51(1H,dd,J=8.4,2.0Hz),7.55-7.67(3H,m),7.70(1H,d,J=8.4Hz),7.90-7.96(2H,m),8.34(1H,d,J=2.0Hz),9.58(1H,s),9.62(1H,s).N- (5- (3-hydroxyphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 6.78-6.84 (1H, m), 7.05-7.13 (2H, m), 7.30 (1H, t , J = 7.8Hz), 7.51 (1H, dd, J = 8.4,2.0Hz), 7.55-7.67 (3H, m), 7.70 (1H, d, J = 8.4Hz), 7.90-7.96 (2H, m) , 8.34 (1H, d, J = 2.0Hz), 9.58 (1H, s), 9.62 (1H, s).
実施例５９
得られたＮ−（５−（１−（ｔｅｒｔ−ブトキシカルボニル）−１Ｈ−ピロール−２−イル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミドにテトラヒドロフラン1.3mLおよび20％ナトリウムエトキシドエタノール溶液0.27mLを加え、室温で1時間30分間攪拌した。反応混合物に水およびジエチルエーテルを加えた。有機層を分取し、飽和塩化ナトリウム水溶液で洗浄後、無水硫酸マグネシウムで乾燥させ、減圧下で溶媒を留去した。得られた残留物をシリカゲルカラムクロマトグラフィー［富士シリシア化学株式会社、Ｐｕｒｉｆ−Ｐａｃｋ ＳＩ（60μm）、溶離液；80-70％ヘキサン／酢酸エチル］で精製し、白色固体のＮ−（２−（メチル（メチルスルホニル）アミノ）−５−（１Ｈ−ピロール−２−イル）フェニル）ベンズアミド15mgを得た。
1H-NMR(DMSO-d6)δ値：3.07(3H,s),3.21(3H,s),6.15(1H,dd,J=5.6,2.5Hz),6.52-6.56(1H,m),6.89(1H,dd,J=4.0,2.5Hz),7.50-7.66(5H,m),7.91-7.95(2H,m),8.20(1H,d,J=2.0Hz),9.55(1H,s),11.41(1H,s).Example 59
The resulting N- (5- (1- (tert-butoxycarbonyl) -1H-pyrrol-2-yl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide was added with 1.3 mL of tetrahydrofuran and 20% sodium ethoxide. Ethanol solution 0.27mL was added and it stirred at room temperature for 1 hour and 30 minutes. Water and diethyl ether were added to the reaction mixture. The organic layer was separated, washed with a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [Fuji Silysia Chemical Ltd., Purif-Pack SI (60 μm), eluent: 80-70% hexane / ethyl acetate], and white solid N- (2- (2- ( 15 mg of methyl (methylsulfonyl) amino) -5- (1H-pyrrol-2-yl) phenyl) benzamide were obtained.
1 H-NMR (DMSO-d 6 ) δ value: 3.07 (3H, s), 3.21 (3H, s), 6.15 (1H, dd, J = 5.6, 2.5 Hz), 6.52-6.56 (1H, m), 6.89 (1H, dd, J = 4.0,2.5Hz), 7.50-7.66 (5H, m), 7.91-7.95 (2H, m), 8.20 (1H, d, J = 2.0Hz), 9.55 (1H, s) 11.41 (1H, s).
実施例６０
得られたＮ−（５−（１−（ｔｅｒｔ−ブトキシカルボニル）インドリン−５−イル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミドに塩化メチレン2.7mLおよびトリフルオロ酢酸0.30mLを加え、室温で3時間攪拌した。減圧下で溶媒を留去し、飽和炭酸水素ナトリウム水溶液および酢酸エチルを加えた。有機層を分取し、飽和塩化ナトリウム水溶液で洗浄後、無水硫酸マグネシウムで乾燥させ、減圧下で溶媒を留去した。得られた残留物にジイソプロピルエーテルを加え、固形物をろ取し、淡赤色固体のＮ−（５−（インドリン−５−イル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド81mgを得た。
1H-NMR(DMSO-d6)δ値：2.99(2H,t,J=8.5Hz),3.09(3H,s),3.23(3H,s),3.48(2H,t,J=8.5Hz),5.74(1H,s),6.58(1H,d,J=8.1Hz),7.27(1H,dd,J=8.1,1.7Hz),7.37(1H,s),7.44(1H,dd,J=8.3,2.2Hz),7.54-7.66(4H,m),7.90-7.95(2H,m),8.27(1H,d,J=2.2Hz),9.50(1H,s).Example 60
To the obtained N- (5- (1- (tert-butoxycarbonyl) indoline-5-yl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide, 2.7 mL of methylene chloride and 0.30 mL of trifluoroacetic acid were added. And stirred at room temperature for 3 hours. The solvent was distilled off under reduced pressure, and a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate were added. The organic layer was separated, washed with a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Diisopropyl ether was added to the obtained residue, and the solid substance was collected by filtration to obtain 81 mg of N- (5- (indoline-5-yl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide as a pale red solid. Obtained.
1 H-NMR (DMSO-d 6 ) δ value: 2.99 (2H, t, J = 8.5Hz), 3.09 (3H, s), 3.23 (3H, s), 3.48 (2H, t, J = 8.5Hz) , 5.74 (1H, s), 6.58 (1H, d, J = 8.1Hz), 7.27 (1H, dd, J = 8.1,1.7Hz), 7.37 (1H, s), 7.44 (1H, dd, J = 8.3 2.2Hz), 7.54-7.66 (4H, m), 7.90-7.95 (2H, m), 8.27 (1H, d, J = 2.2Hz), 9.50 (1H, s).
実施例６１
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.26(3H,s),7.56-7.67(3H,m),7.77(1H,d,J=8.3Hz),7.83-7.88(2H,m),7.91-7.96(2H,m),7.99(1H,d,J=3.2Hz),8.73(1H,d,J=2.2Hz),9.66(1H,s).Example 61
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.26 (3H, s), 7.56-7.67 (3H, m), 7.77 (1H, d, J = 8.3 Hz), 7.83 7.88 (2H, m), 7.91-7.96 (2H, m), 7.99 (1H, d, J = 3.2Hz), 8.73 (1H, d, J = 2.2Hz), 9.66 (1H, s).
実施例６２
1H-NMR(DMSO-d6)δ値：1.94-2.04(2H,m),2.64-2.72(2H,m),3.06(3H,s),3.20(3H,s),6.32-6.36(1H,m),7.39(1H,dd,J=8.3,2.0Hz),7.52-7.66(5H,m),7.87-7.94(3H,m),8.11(1H,d,J=2.0Hz),9.52(1H,s).Example 62
1 H-NMR (DMSO-d 6 ) δ value: 1.94.2.44 (2H, m), 2.64-2.72 (2H, m), 3.06 (3H, s), 3.20 (3H, s), 6.32-6.36 (1H , m), 7.39 (1H, dd, J = 8.3, 2.0Hz), 7.52-7.66 (5H, m), 7.87-7.94 (3H, m), 8.11 (1H, d, J = 2.0Hz), 9.52 ( 1H, s).
実施例６３
1H-NMR(DMSO-d6)δ値：1.50-1.85(6H,m),2.00-2.10(2H,m),2.96-3.07(1H,m),3.06(3H,s),3.19(3H,s),7.17(1H,dd,J=8.3,2.0Hz),7.50-7.65(4H,m),7.87-7.92(2H,m),7.98(1H,d,J=2.0Hz),9.45(1H,s).Example 63
1 H-NMR (DMSO-d 6 ) δ value: 1.50-1.85 (6H, m), 2.00-2.10 (2H, m), 2.96-3.07 (1H, m), 3.06 (3H, s), 3.19 (3H , s), 7.17 (1H, dd, J = 8.3, 2.0Hz), 7.50-7.65 (4H, m), 7.87-7.92 (2H, m), 7.98 (1H, d, J = 2.0Hz), 9.45 ( 1H, s).
実施例６４
1H-NMR(DMSO-d6)δ値：3.08(3H,s),3.12(2H,t,J=8.4Hz),3.22(3H,s),3.98(2H,t,J=8.4Hz),6.78(1H,t,J=7.3Hz),7.03(1H,dd,J=8.8,2.7Hz),7.11(1H,t,J=7.4Hz),7.22(1H,d,J=7.1Hz),7.29(1H,d,J=8.0Hz),7.54-7.66(4H,m),7.89-7.94(2H,m),8.14(1H,d,J=2.7Hz),9.45(1H,s).Example 64
1 H-NMR (DMSO-d 6 ) δ value: 3.08 (3H, s), 3.12 (2H, t, J = 8.4 Hz), 3.22 (3H, s), 3.98 (2H, t, J = 8.4 Hz) , 6.78 (1H, t, J = 7.3Hz), 7.03 (1H, dd, J = 8.8, 2.7Hz), 7.11 (1H, t, J = 7.4Hz), 7.22 (1H, d, J = 7.1Hz) , 7.29 (1H, d, J = 8.0Hz), 7.54-7.66 (4H, m), 7.89-7.94 (2H, m), 8.14 (1H, d, J = 2.7Hz), 9.45 (1H, s).
実施例６５〜６７
実施例６４と同様にして、表１５に示す化合物を得た。Examples 65-67
In the same manner as in Example 64, the compounds shown in Table 15 were obtained.
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（ピペジリン−１−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：1.53-1.67(6H,m),3.03(3H,s),3.16(3H,s),3.18-3.23(4H,m),6.80(1H,dd,J=8.8,2.6Hz),7.41(1H,d,J=8.8Hz),7.53-7.65(3H,m),7.72(1H,d,J=2.6Hz),7.86-7.91(2H,m),9.32(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (piperidin-1-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 1.53-1.67 (6H, m), 3.03 (3H, s), 3.16 (3H, s), 3.18-3.23 (4H, m), 6.80 (1H, dd , J = 8.8,2.6Hz), 7.41 (1H, d, J = 8.8Hz), 7.53-7.65 (3H, m), 7.72 (1H, d, J = 2.6Hz), 7.86-7.91 (2H, m) , 9.32 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−メチルピペラジン−１−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.23(3H,s),2.43-2.49(4H,m),3.03(3H,s),3.17(3H,s),3.16-3.22(4H,m),6.82(1H,dd,J=8.9,2.3Hz),7.43(1H,d,J=8.9Hz),7.53-7.65(3H,m),7.72(1H,d,J=2.3Hz),7.85-7.92(2H,m),9.35(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (4-methylpiperazin-1-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.23 (3H, s), 2.43-2.49 (4H, m), 3.03 (3H, s), 3.17 (3H, s), 3.16-3.22 (4H, m ), 6.82 (1H, dd, J = 8.9,2.3Hz), 7.43 (1H, d, J = 8.9Hz), 7.53-7.65 (3H, m), 7.72 (1H, d, J = 2.3Hz), 7.85 -7.92 (2H, m), 9.35 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（１，２，３，４−テトラヒドロイソキノリン−２−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.95(2H,t,J=5.7Hz),3.04(3H,s),3.17(3H,s),3.59(2H,t,J=5.7Hz),4.45(2H,s),6.88(1H,dd,J=8.8,2.4Hz),7.16-7.28(4H,m),7.45(1H,d,J=8.8Hz),7.53-7.65(3H,m),7.76(1H,d,J=2.4Hz),7.87-7.94(2H,m),9.37(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (1,2,3,4-tetrahydroisoquinolin-2-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.95 (2H, t, J = 5.7 Hz), 3.04 (3H, s), 3.17 (3H, s), 3.59 (2H, t, J = 5.7 Hz) , 4.45 (2H, s), 6.88 (1H, dd, J = 8.8,2.4Hz), 7.16-7.28 (4H, m), 7.45 (1H, d, J = 8.8Hz), 7.53-7.65 (3H, m ), 7.76 (1H, d, J = 2.4Hz), 7.87-7.94 (2H, m), 9.37 (1H, s).
実施例６８
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),5.24(2H,s),6.60(1H,dd,J=7.9,1.4Hz),6.80(1H,d,J=7.8Hz),6.88(1H,s),7.13(1H,t,J=7.8Hz),7.46(1H,dd,J=8.3,2.0Hz),7.55-7.70(4H,m),7.90-7.95(2H,m),8.31(1H,d,J=2.0Hz),9.56(1H,s).Example 68
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 5.24 (2H, s), 6.60 (1H, dd, J = 7.9, 1.4 Hz), 6.80 ( 1H, d, J = 7.8Hz), 6.88 (1H, s), 7.13 (1H, t, J = 7.8Hz), 7.46 (1H, dd, J = 8.3,2.0Hz), 7.55-7.70 (4H, m ), 7.90-7.95 (2H, m), 8.31 (1H, d, J = 2.0Hz), 9.56 (1H, s).
実施例６９
Ｎ−（５−（４−アミノフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.23(3H,s),5.33(2H,s),6.64-6.70(2H,m),7.36-7.42(2H,m),7.44(1H,dd,J=8.4,2.0Hz),7.54-7.66(4H,m),7.89-7.96(2H,m),8.25(1H,d,J=2.0Hz),9.51(1H,s).Example 69
N- (5- (4-aminophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.23 (3H, s), 5.33 (2H, s), 6.64-6.70 (2H, m), 7.36-7.42 (2H, m ), 7.44 (1H, dd, J = 8.4,2.0Hz), 7.54-7.66 (4H, m), 7.89-7.96 (2H, m), 8.25 (1H, d, J = 2.0Hz), 9.51 (1H, s).
実施例７０
Ｎ−（５−（４−エチルフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：1.22(3H,t,J=7.6Hz),2.66(2H,q,J=7.6Hz),3.11(3H,s),3.25(3H,s),7.32-7.38(2H,m),7.53-7.67(6H,m),7.71(1H,d,J=8.3Hz),7.90-7.96(2H,m),8.36(1H,d,J=2.2Hz),9.59(1H,s).Example 70
N- (5- (4-Ethylphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 1.22 (3H, t, J = 7.6 Hz), 2.66 (2H, q, J = 7.6 Hz), 3.11 (3H, s), 3.25 (3H, s) , 7.32-7.38 (2H, m), 7.53-7.67 (6H, m), 7.71 (1H, d, J = 8.3Hz), 7.90-7.96 (2H, m), 8.36 (1H, d, J = 2.2Hz ), 9.59 (1H, s).
実施例７１
1H-NMR(DMSO-d6)δ値：2.76(3H,s),2.96(2H,t,J=8.2Hz),3.09(3H,s),3.23(3H,s),3.28-3.36(2H,m),6.60(1H,d,J=8.1Hz),7.34-7.41(2H,m),7.46(1H,dd,J=8.6,2.2Hz),7.54-7.66(4H,m),7.89-7.95(2H,m),8.28(1H,d,J=2.2Hz),9.51(1H,s).Example 71
1 H-NMR (DMSO-d 6 ) δ value: 2.76 (3H, s), 2.96 (2H, t, J = 8.2 Hz), 3.09 (3H, s), 3.23 (3H, s), 3.28-3.36 ( 2H, m), 6.60 (1H, d, J = 8.1Hz), 7.34-7.41 (2H, m), 7.46 (1H, dd, J = 8.6,2.2Hz), 7.54-7.66 (4H, m), 7.89 -7.95 (2H, m), 8.28 (1H, d, J = 2.2Hz), 9.51 (1H, s).
実施例７２
Ｎ−（５−（２−（ジメチルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.53(6H,s),3.10(3H,s),3.25(3H,s),7.04(1H,t,J=7.3Hz),7.10(1H,d,J=8.0Hz),7.22(1H,d,J=7.6Hz),7.27-7.34(1H,m),7.45(1H,dd,J=8.3,1.2Hz),7.53-7.68(4H,m),7.89-7.94(2H,m),8.20-8.25(1H,m),9.54(1H,s).Example 72
N- (5- (2- (dimethylamino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.53 (6H, s), 3.10 (3H, s), 3.25 (3H, s), 7.04 (1H, t, J = 7.3 Hz), 7.10 (1H, d, J = 8.0Hz), 7.22 (1H, d, J = 7.6Hz), 7.27-7.34 (1H, m), 7.45 (1H, dd, J = 8.3,1.2Hz), 7.53-7.68 (4H, m ), 7.89-7.94 (2H, m), 8.20-8.25 (1H, m), 9.54 (1H, s).
実施例７３
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.26(3H,s),4.92(2H,s),6.63-6.70(1H,m),6.79(1H,d,J=8.0Hz),7.03-7.12(2H,m),7.34(1H,dd,J=8.3,2.1Hz),7.54-7.66(3H,m),7.70(1H,d,J=8.3Hz),7.89-7.94(2H,m),8.17(1H,d,J=2.1Hz),9.56(1H,s).Example 73
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.26 (3H, s), 4.92 (2H, s), 6.63 to 6.70 (1H, m), 6.79 (1H, d, J = 8.0Hz), 7.03-7.12 (2H, m), 7.34 (1H, dd, J = 8.3,2.1Hz), 7.54-7.66 (3H, m), 7.70 (1H, d, J = 8.3Hz), 7.89 -7.94 (2H, m), 8.17 (1H, d, J = 2.1Hz), 9.56 (1H, s).
実施例７４
Ｎ−（５−（４−（メチルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.72(3H,d,J=5.1Hz),3.09(3H,s),3.23(3H,s),5.91(1H,q,J=5.1Hz),6.62-6.68(2H,m),7.43-7.49(3H,m),7.54-7.66(4H,m),7.90-7.95(2H,m),8.26(1H,d,J=2.2Hz),9.52(1H,s).Example 74
N- (5- (4- (methylamino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.72 (3H, d, J = 5.1 Hz), 3.09 (3H, s), 3.23 (3H, s), 5.91 (1H, q, J = 5.1 Hz) , 6.62-6.68 (2H, m), 7.43-7.49 (3H, m), 7.54-7.66 (4H, m), 7.90-7.95 (2H, m), 8.26 (1H, d, J = 2.2Hz), 9.52 (1H, s).
実施例７５
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.24(3H,s),6.32(2H,t,J=2.1Hz),7.37(2H,t,J=2.1Hz),7.49(1H,dd,J=8.8,2.7Hz),7.55-7.67(3H,m),7.72(1H,d,J=8.8Hz),7.90-7.96(2H,m),8.27(1H,d,J=2.7Hz),9.62(1H,s).Example 75
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.24 (3H, s), 6.32 (2H, t, J = 2.1 Hz), 7.37 (2H, t, J = 2.1 Hz) , 7.49 (1H, dd, J = 8.8,2.7Hz), 7.55-7.67 (3H, m), 7.72 (1H, d, J = 8.8Hz), 7.90-7.96 (2H, m), 8.27 (1H, d , J = 2.7Hz), 9.62 (1H, s).
実施例７６
３−クロロ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（１Ｈ−ピロール−１イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.07(3H,s),3.23(3H,s),6.31(2H,t,J=2.1Hz),7.38(2H,t,J=2.1Hz),7.52(1H,dd,J=8.6,2.7Hz),7.61(1H,t,J=7.9Hz),7.68-7.75(2H,m),7.87(1H,d,J=7.8Hz),7.93-7.97(1H,m),8.12(1H,d,J=2.7Hz),9.85(1H,s).Example 76
3-Chloro-N- (2- (methyl (methylsulfonyl) amino) -5- (1H-pyrrol-1-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.07 (3H, s), 3.23 (3H, s), 6.31 (2H, t, J = 2.1 Hz), 7.38 (2H, t, J = 2.1 Hz) , 7.52 (1H, dd, J = 8.6,2.7Hz), 7.61 (1H, t, J = 7.9Hz), 7.68-7.75 (2H, m), 7.87 (1H, d, J = 7.8Hz), 7.93- 7.97 (1H, m), 8.12 (1H, d, J = 2.7Hz), 9.85 (1H, s).
実施例７７
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.27(3H,s),7.32-7.40(2H,m),7.44-7.51(2H,m),7.54-7.66(4H,m),7.75(1H,d,J=8.3Hz),7.90-7.95(2H,m),8.28(1H,s),9.62(1H,s).Example 77
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.27 (3H, s), 7.32-7.40 (2H, m), 7.44-7.51 (2H, m), 7.54-7.66 (4H , m), 7.75 (1H, d, J = 8.3Hz), 7.90-7.95 (2H, m), 8.28 (1H, s), 9.62 (1H, s).
実施例７８
３−クロロ−Ｎ−（５−（２−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.25(3H,s),7.32-7.39(2H,m),7.44-7.52(2H,m),7.54-7.64(2H,m),7.67-7.72(1H,m),7.74(1H,d,J=8.3Hz),7.84-7.89(1H,m),7.94(1H,t,J=1.7Hz),8.12(1H,s),9.84(1H,s)Example 78
3-Chloro-N- (5- (2-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.25 (3H, s), 7.32-7.39 (2H, m), 7.44-7.52 (2H, m), 7.54-7.64 (2H , m), 7.67-7.72 (1H, m), 7.74 (1H, d, J = 8.3Hz), 7.84-7.89 (1H, m), 7.94 (1H, t, J = 1.7Hz), 8.12 (1H, s), 9.84 (1H, s)
実施例７９
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.24(3H,s),7.18(1H,dd,J=5.1,3.7Hz),7.55-7.69(7H,m),7.90-7.96(2H,m),8.37(1H,d,J=2.0Hz),9.59(1H,s).Example 79
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.24 (3H, s), 7.18 (1H, dd, J = 5.1, 3.7 Hz), 7.55-7.69 (7H, m), 7.90-7.96 (2H, m), 8.37 (1H, d, J = 2.0Hz), 9.59 (1H, s).
実施例８０
３−クロロ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（チオフェン−２−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.07(3H,s),3.22(3H,s),7.18(1H,dd,J=5.1,3.7Hz),7.57(1H,dd,J=3.7,1.0Hz),7.58-7.72(5H,m),7.85-7.89(1H,m),7.95(1H,t,J=1.8Hz),8.21(1H,d,J=1.9Hz),9.81(1H,s).Example 80
3-Chloro-N- (2- (methyl (methylsulfonyl) amino) -5- (thiophen-2-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.07 (3H, s), 3.22 (3H, s), 7.18 (1H, dd, J = 5.1, 3.7 Hz), 7.57 (1H, dd, J = 3.7 , 1.0Hz), 7.58-7.72 (5H, m), 7.85-7.89 (1H, m), 7.95 (1H, t, J = 1.8Hz), 8.21 (1H, d, J = 1.9Hz), 9.81 (1H , s).
実施例８１
1H-NMR(DMSO-d6)δ値：3.13(3H,s),3.26(3H,s),7.43-7.67(8H,m),7.76(1H,d,J=11.2Hz),7.89-7.95(2H,m),8.12(1H,d,J=8.3Hz),9.64(1H,s).Example 81
1 H-NMR (DMSO-d 6 ) δ value: 3.13 (3H, s), 3.26 (3H, s), 7.43-7.67 (8H, m), 7.76 (1H, d, J = 11.2Hz), 7.89- 7.95 (2H, m), 8.12 (1H, d, J = 8.3Hz), 9.64 (1H, s).
実施例８２〜８４
実施例８１と同様にして、表１６に示す化合物を得た。Examples 82-84
In the same manner as in Example 81, the compounds shown in Table 16 were obtained.
Ｎ−（４−フルオロ−２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.20(3H,s),3.30(3H,s),4.10(3H,s),7.15(1H,t,J=7.6Hz),7.29(1H,d,J=8.5Hz),7.44-7.65(6H,m),7.79(1H,d,J=11.0Hz),8.11(1H,dd,J=7.8,1.7Hz),8.71(1H,d,J=8.6Hz),10.76(1H,s).N- (4-Fluoro-2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.20 (3H, s), 3.30 (3H, s), 4.10 (3H, s), 7.15 (1H, t, J = 7.6 Hz), 7.29 (1H, d, J = 8.5Hz), 7.44-7.65 (6H, m), 7.79 (1H, d, J = 11.0Hz), 8.11 (1H, dd, J = 7.8,1.7Hz), 8.71 (1H, d, J = 8.6Hz), 10.76 (1H, s).
Ｎ−（４−フルオロ−２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−３−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.13(3H,s),3.25(3H,s),3.83(3H,s),7.16-7.22(1H,m),7.43-7.62(8H,m),7.76(1H,d,J=11.2Hz),8.13(1H,d,J=8.3Hz),9.62(1H,s).N- (4-Fluoro-2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -3-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.13 (3H, s), 3.25 (3H, s), 3.83 (3H, s), 7.16-7.22 (1H, m), 7.43-7.62 (8H, m ), 7.76 (1H, d, J = 11.2Hz), 8.13 (1H, d, J = 8.3Hz), 9.62 (1H, s).
Ｎ−（４−フルオロ−２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−４−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.13(3H,s),3.25(3H,s),3.85(3H,s),7.10(2H,d,J=8.8Hz),7.43-7.62(5H,m),7.74(1H,d,J=11.2Hz),7.89(2H,d,J=8.8Hz),8.14(1H,d,J=8.3Hz),9.47(1H,s).N- (4-Fluoro-2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -4-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.13 (3H, s), 3.25 (3H, s), 3.85 (3H, s), 7.10 (2H, d, J = 8.8 Hz), 7.43-7.62 ( 5H, m), 7.74 (1H, d, J = 11.2Hz), 7.89 (2H, d, J = 8.8Hz), 8.14 (1H, d, J = 8.3Hz), 9.47 (1H, s).
実施例８５
1H-NMR(DMSO-d6)δ値：2.78(6H,s),3.18(3H,s),3.30(3H,s),7.25-7.31(1H,m),7.44-7.50(2H,m),7.51-7.62(5H,m),7.77(1H,d,J=11.2Hz),8.07(1H,dd,J=7.9,1.6Hz),8.79(1H,d,J=8.6Hz),12.62(1H,s).Example 85
1 H-NMR (DMSO-d 6 ) δ value: 2.78 (6H, s), 3.18 (3H, s), 3.30 (3H, s), 7.25 to 7.31 (1H, m), 7.44 to 7.50 (2H, m ), 7.51-7.62 (5H, m), 7.77 (1H, d, J = 11.2Hz), 8.07 (1H, dd, J = 7.9,1.6Hz), 8.79 (1H, d, J = 8.6Hz), 12.62 (1H, s).
実施例８６
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.24(3H,s),7.01(1H,d,J=2.0Hz),7.38-7.44(1H,m),7.47-7.54(2H,m),7.55-7.67(5H,m),7.89-7.94(3H,m),9.38(1H,s),10.59(1H,s).Example 86
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.24 (3H, s), 7.01 (1H, d, J = 2.0 Hz), 7.38-7.44 (1H, m), 7.47- 7.54 (2H, m), 7.55-7.67 (5H, m), 7.89-7.94 (3H, m), 9.38 (1H, s), 10.59 (1H, s).
実施例８７
1H-NMR(DMSO-d6)δ値：3.07(3H,s),3.20(3H,s),4.00(3H,s),7.20(1H,d,J=2.0Hz),7.40-7.46(1H,m),7.48-7.67(5H,m),7.69-7.75(2H,m),7.89-7.95(2H,m),8.01(1H,d,J=2.0Hz),9.45(1H,s).Example 87
1 H-NMR (DMSO-d 6 ) δ value: 3.07 (3H, s), 3.20 (3H, s), 4.00 (3H, s), 7.20 (1H, d, J = 2.0 Hz), 7.40-7.46 ( 1H, m), 7.48-7.67 (5H, m), 7.69-7.75 (2H, m), 7.89-7.95 (2H, m), 8.01 (1H, d, J = 2.0Hz), 9.45 (1H, s) .
実施例８８
1H-NMR(DMSO-d6)δ値：3.15(3H,s),3.28(3H,s),3.84(3H,s),7.31(1H,s),7.33-7.40(1H,m),7.41-7.64(7H,m),7.86(1H,s),7.87-7.93(2H,m),9.49(1H,s).Example 88
1 H-NMR (DMSO-d 6 ) δ value: 3.15 (3H, s), 3.28 (3H, s), 3.84 (3H, s), 7.31 (1H, s), 7.33-7.40 (1H, m), 7.41-7.64 (7H, m), 7.86 (1H, s), 7.87-7.93 (2H, m), 9.49 (1H, s).
実施例８９
1H-NMR(DMSO-d6)δ値：3.04(3H,s),3.23(3H,s),7.43-7.65(6H,m),7.94-8.02(3H,m),8.05-8.11(2H,m),8.14(1H,d,J=8.3Hz),10.48(1H,s).Example 89
1 H-NMR (DMSO-d 6 ) δ value: 3.04 (3H, s), 3.23 (3H, s), 7.43-7.65 (6H, m), 7.94-8.02 (3H, m), 8.05-8.11 (2H , m), 8.14 (1H, d, J = 8.3Hz), 10.48 (1H, s).
実施例９０
1H-NMR(DMSO-d6)δ値：3.06(3H,s),3.18(3H,s),6.87-6.93(2H,m),7.13-7.18(2H,m),7.25-7.32(2H,m),7.44(1H,d,J=8.8Hz),7.54-7.65(3H,m),7.86-7.92(2H,m),7.93(1H,d,J=2.7Hz),8.48(1H,s),9.33(1H,s).Example 90
1 H-NMR (DMSO-d 6 ) δ value: 3.06 (3H, s), 3.18 (3H, s), 6.87-6.93 (2H, m), 7.13-7.18 (2H, m), 7.25-7.32 (2H , m), 7.44 (1H, d, J = 8.8Hz), 7.54-7.65 (3H, m), 7.86-7.92 (2H, m), 7.93 (1H, d, J = 2.7Hz), 8.48 (1H, s), 9.33 (1H, s).
実施例９１
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.23(3H,s),7.26-7.34(3H,m),7.37-7.44(2H,m),7.53-7.69(7H,m),7.91-7.96(2H,m),8.25(1H,d,J=1.2Hz),9.57(1H,s).Example 91
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.23 (3H, s), 7.26-7.34 (3H, m), 7.37-7.44 (2H, m), 7.53-7.69 (7H , m), 7.91-7.96 (2H, m), 8.25 (1H, d, J = 1.2Hz), 9.57 (1H, s).
実施例９２
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェネチルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.92(4H,s),3.05(3H,s),3.20(3H,s),7.15-7.23(2H,m),7.28-7.31(4H,m),7.51-7.65(4H,m),7.88-7.93(2H,m),8.00(1H,d,J=1.9Hz),9.48(1H,s).Example 92
N- (2- (methyl (methylsulfonyl) amino) -5-phenethylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.92 (4H, s), 3.05 (3H, s), 3.20 (3H, s), 7.15-7.23 (2H, m), 7.28-7.31 (4H, m ), 7.51-7.65 (4H, m), 7.88-7.93 (2H, m), 8.00 (1H, d, J = 1.9Hz), 9.48 (1H, s).
実施例９３
1H-NMR(DMSO-d6)δ値：3.15(3H,s),3.19(3H,s),4.76(2H,s),7.02(1H,t,J=7.2Hz),7.07-7.12(2H,m),7.32-7.45(3H,m),7.48-7.55(3H,m),7.63-7.68(2H,m),7.72(1H,d,J=8.3Hz),8.52(1H,d,J=2.0Hz),9.60(1H,s).Example 93
1 H-NMR (DMSO-d 6 ) δ value: 3.15 (3H, s), 3.19 (3H, s), 4.76 (2H, s), 7.02 (1H, t, J = 7.2 Hz), 7.07-7.12 ( 2H, m), 7.32-7.45 (3H, m), 7.48-7.55 (3H, m), 7.63-7.68 (2H, m), 7.72 (1H, d, J = 8.3Hz), 8.52 (1H, d, J = 2.0Hz), 9.60 (1H, s).
実施例９４〜１１０
実施例９３と同様にして、表１７に示す化合物を得た。Examples 94-110
In the same manner as in Example 93, the compounds shown in Table 17 were obtained.
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２−フェニルアセトアミド
1H-NMR(DMSO-d6)δ値：3.05(3H,s),3.13(3H,s),3.79(2H,s),7.23-7.53(9H,m),7.57-7.68(3H,m),8.29(1H,s),9.20(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2-phenylacetamide
1 H-NMR (DMSO-d 6 ) δ value: 3.05 (3H, s), 3.13 (3H, s), 3.79 (2H, s), 7.23-7.53 (9H, m), 7.57-7.68 (3H, m ), 8.29 (1H, s), 9.20 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）シンナムアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.24(3H,s),7.21(1H,d,J=15.6Hz),7.39-7.54(7H,m),7.60(1H,d,J=15.6Hz),7.64-7.71(5H,m),8.51-8.56(1H,m),9.35(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) cinnamamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.24 (3H, s), 7.21 (1H, d, J = 15.6 Hz), 7.39-7.54 (7H, m), 7.60 ( 1H, d, J = 15.6Hz), 7.64-7.71 (5H, m), 8.51-8.56 (1H, m), 9.35 (1H, s).
２−クロロ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.21(3H,s),7.40-7.61(7H,m),7.65-7.73(4H,m),8.30(1H,s),9.82(1H,s).2-Chloro-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.21 (3H, s), 7.40-7.61 (7H, m), 7.65-7.73 (4H, m), 8.30 (1H, s ), 9.82 (1H, s).
３−クロロ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.25(3H,s),7.42(1H,t,J=7.3Hz),7.48-7.55(2H,m),7.58-7.64(2H,m),7.67-7.74(4H,m),7.85-7.91(1H,m),7.96(1H,t,J=1.7Hz),8.22(1H,d,J=2.2Hz),9.82(1H,s).3-Chloro-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.25 (3H, s), 7.42 (1H, t, J = 7.3 Hz), 7.48-7.55 (2H, m), 7.58- 7.64 (2H, m), 7.67-7.74 (4H, m), 7.85-7.91 (1H, m), 7.96 (1H, t, J = 1.7Hz), 8.22 (1H, d, J = 2.2Hz), 9.82 (1H, s).
４−クロロ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.24(3H,s),7.39-7.45(1H,m),7.48-7.55(2H,m),7.57-7.75(6H,m),7.92-7.98(2H,m),8.24-8.28(1H,m),9.72(1H,s).4-Chloro-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.24 (3H, s), 7.39-7.45 (1H, m), 7.48-7.55 (2H, m), 7.57-7.75 (6H , m), 7.92-7.98 (2H, m), 8.24-8.28 (1H, m), 9.72 (1H, s).
２−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.45(3H,s),3.09(3H,s),3.22(3H,s),7.28-7.36(2H,m),7.38-7.45(2H,m),7.49-7.59(4H,m),7.66-7.73(3H,m),8.34(1H,s),9.46(1H,s).2-Methyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.45 (3H, s), 3.09 (3H, s), 3.22 (3H, s), 7.28-7.36 (2H, m), 7.38-7.45 (2H, m ), 7.49-7.59 (4H, m), 7.66-7.73 (3H, m), 8.34 (1H, s), 9.46 (1H, s).
３−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.41(3H,s),3.12(3H,s),3.26(3H,s),7.39-7.54(5H,m),7.57(1H,dd,J=8.3,2.2Hz),7.67-7.77(5H,m),8.36(1H,d,J=2.2Hz),9.56(1H,s).3-Methyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.41 (3H, s), 3.12 (3H, s), 3.26 (3H, s), 7.39-7.54 (5H, m), 7.57 (1H, dd, J = 8.3, 2.2Hz), 7.67-7.77 (5H, m), 8.36 (1H, d, J = 2.2Hz), 9.56 (1H, s).
４−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.40(3H,s),3.11(3H,s),3.26(3H,s),7.36-7.45(3H,m),7.48-7.54(2H,m),7.56(1H,dd,J=8.3,2.1Hz),7.66-7.74(3H,m),7.81-7.86(2H,m),8.39(1H,d,J=2.1Hz),9.50(1H,s).4-Methyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.40 (3H, s), 3.11 (3H, s), 3.26 (3H, s), 7.36-7.45 (3H, m), 7.48-7.54 (2H, m ), 7.56 (1H, dd, J = 8.3,2.1Hz), 7.66-7.74 (3H, m), 7.81-7.86 (2H, m), 8.39 (1H, d, J = 2.1Hz), 9.50 (1H, s).
４−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.26(3H,s),3.85(3H,s),7.09-7.14(2H,m),7.39-7.44(1H,m),7.48-7.57(3H,m),7.66-7.74(3H,m),7.87-7.93(2H,m),8.40(1H,d,J=2.0Hz),9.44(1H,s).4-Methoxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.26 (3H, s), 3.85 (3H, s), 7.09-7.14 (2H, m), 7.39-7.44 (1H, m ), 7.48-7.57 (3H, m), 7.66-7.74 (3H, m), 7.87-7.93 (2H, m), 8.40 (1H, d, J = 2.0Hz), 9.44 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ピリジン−２−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.20(3H,s),3.29(3H,s),7.40-7.46(1H,m),7.50-7.56(3H,m),7.67-7.77(4H,m),8.12(1H,td,J=7.7,1.7Hz),8.20-8.25(1H,m),8.73-8.77(1H,d),8.82(1H,d,J=2.2Hz),10.86(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) pyridine-2-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.20 (3H, s), 3.29 (3H, s), 7.40-7.46 (1H, m), 7.50-7.56 (3H, m), 7.67-7.77 (4H , m), 8.12 (1H, td, J = 7.7, 1.7Hz), 8.20-8.25 (1H, m), 8.73-8.77 (1H, d), 8.82 (1H, d, J = 2.2Hz), 10.86 ( 1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ピリジン−３−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.25(3H,s),7.39-7.45(1H,m),7.48-7.54(2H,m),7.58-7.64(2H,m),7.67-7.75(3H,m),8.23-8.29(2H,m),8.80(1H,dd,J=4.9,1.7Hz),9.10(1H,d,J=2.2Hz),9.93(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) pyridine-3-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.25 (3H, s), 7.39-7.45 (1H, m), 7.48-7.54 (2H, m), 7.58-7.64 (2H , m), 7.67-7.75 (3H, m), 8.23-8.29 (2H, m), 8.80 (1H, dd, J = 4.9, 1.7Hz), 9.10 (1H, d, J = 2.2Hz), 9.93 ( 1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ピリジン−４−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.25(3H,s),7.39-7.45(1H,m),7.48-7.55(2H,m),7.62(1H,dd,J=8.3,2.2Hz),7.67-7.75(3H,m),7.80-7.85(2H,m),8.21(1H,d,J=1.7Hz),8.80-8.85(2H,m),9.97(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) pyridine-4-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.25 (3H, s), 7.39-7.45 (1H, m), 7.48-7.55 (2H, m), 7.62 (1H, dd , J = 8.3,2.2Hz), 7.67-7.75 (3H, m), 7.80-7.85 (2H, m), 8.21 (1H, d, J = 1.7Hz), 8.80-8.85 (2H, m), 9.97 ( 1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）フラン−２−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.14(3H,s),3.27(3H,s),6.76(1H,dd,J=3.4,1.7Hz),7.28-7.32(1H,m),7.39-7.45(1H,m),7.48-7.55(2H,m),7.56(1H,dd,J=8.3,2.1Hz),7.65-7.71(2H,m),7.74(1H,d,J=8.3Hz),8.01(1H,dd,J=1.7,0.7Hz),8.45(1H,d,J=2.1Hz),9.37(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) furan-2-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.14 (3H, s), 3.27 (3H, s), 6.76 (1H, dd, J = 3.4, 1.7 Hz), 7.28-7.32 (1H, m), 7.39-7.45 (1H, m), 7.48-7.55 (2H, m), 7.56 (1H, dd, J = 8.3,2.1Hz), 7.65-7.71 (2H, m), 7.74 (1H, d, J = 8.3 Hz), 8.01 (1H, dd, J = 1.7,0.7Hz), 8.45 (1H, d, J = 2.1Hz), 9.37 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）チオフェン−２−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.26(3H,m),7.27(1H,dd,J=4.9,3.8Hz),7.39-7.45(1H,m),7.48-7.54(2H,m),7.58(1H,dd,J=8.3,2.1Hz),7.66-7.74(3H,m),7.81-7.86(1H,m),7.91(1H,dd,J=4.9,1.0Hz),8.25(1H,d,J=2.1Hz),9.57(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) thiophene-2-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.26 (3H, m), 7.27 (1H, dd, J = 4.9, 3.8 Hz), 7.39-7.45 (1H, m), 7.48-7.54 (2H, m), 7.58 (1H, dd, J = 8.3,2.1Hz), 7.66-7.74 (3H, m), 7.81-7.86 (1H, m), 7.91 (1H, dd, J = 4.9 , 1.0Hz), 8.25 (1H, d, J = 2.1Hz), 9.57 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）シクロヘキサンカルボキサミド
1H-NMR(DMSO-d6)δ値：1.12-1.46(5H,m),1.61-1.69(1H,m),1.70-1.79(2H,m),1.83-1.91(2H,m),2.44-2.52(1H,m),3.08(3H,s),3.19(3H,s),7.37-7.43(1H,m),7.44-7.52(3H,m),7.60-7.66(3H,m),8.30(1H,d,J=1.7Hz),8.95(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) cyclohexanecarboxamide
1 H-NMR (DMSO-d 6 ) δ value: 1.12-1.46 (5H, m), 1.61-1.69 (1H, m), 1.70-1.79 (2H, m), 1.83-1.91 (2H, m), 2.44 -2.52 (1H, m), 3.08 (3H, s), 3.19 (3H, s), 7.37-7.43 (1H, m), 7.44-7.52 (3H, m), 7.60-7.66 (3H, m), 8.30 (1H, d, J = 1.7Hz), 8.95 (1H, s).
２−（４−メトキシフェニル）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）アセトアミド
1H-NMR(DMSO-d6)δ値：3.04(3H,s),3.12(3H,s),3.71(2H,s),3.74(3H,s),6.90(2H,d,J=8.6Hz),7.28(2H,d,J=8.6Hz),7.37-7.51(4H,m),7.58-7.65(3H,m),8.28-8.34(1H,m),9.08(1H,s).2- (4-Methoxyphenyl) -N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) acetamide
1 H-NMR (DMSO-d 6 ) δ value: 3.04 (3H, s), 3.12 (3H, s), 3.71 (2H, s), 3.74 (3H, s), 6.90 (2H, d, J = 8.6 Hz), 7.28 (2H, d, J = 8.6Hz), 7.37-7.51 (4H, m), 7.58-7.65 (3H, m), 8.28-8.34 (1H, m), 9.08 (1H, s).
トランス−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２−フェニルシクロプロパン−１−カルボキサミド
1H-NMR(DMSO-d6)δ値：1.34-1.42(1H,m),1.45-1.53(1H,m),2.37-2.53(2H,m),3.08(3H,s),3.19(3H,s),7.17-7.24(3H,m),7.27-7.33(2H,m),7.37-7.53(4H,m),7.59-7.67(3H,m),8.35-8.44(1H,broad),9.51(1H,s).Trans-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2-phenylcyclopropane-1-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 1.34-1.42 (1H, m), 1.45-1.53 (1H, m), 2.37-2.53 (2H, m), 3.08 (3H, s), 3.19 (3H , s), 7.17-7.24 (3H, m), 7.27-7.33 (2H, m), 7.37-7.53 (4H, m), 7.59-7.67 (3H, m), 8.35-8.44 (1H, broad), 9.51 (1H, s).
実施例１１１
1H-NMR(DMSO-d6)δ値：3.14(3H,s),3.25(3H,s),7.38-7.56(5H,m),7.56(1H,dd,J=8.3,2.2Hz),7.62-7.72(3H,m),7.74(1H,d,J=8.3Hz),7.98(1H,td,J=7.7,1.7Hz),8.56-8.61(1H,m),9.73(1H,d,J=10.2Hz).Example 111
1 H-NMR (DMSO-d 6 ) δ value: 3.14 (3H, s), 3.25 (3H, s), 7.38-7.56 (5H, m), 7.56 (1H, dd, J = 8.3, 2.2 Hz), 7.62-7.72 (3H, m), 7.74 (1H, d, J = 8.3Hz), 7.98 (1H, td, J = 7.7,1.7Hz), 8.56-8.61 (1H, m), 9.73 (1H, d, J = 10.2Hz).
実施例１１２〜１２４
実施例１１１と同様にして、表１８に示す化合物を得た。Examples 112-124
In the same manner as in Example 111, the compounds shown in Table 18 were obtained.
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−３−フェニルプロパンアミド
1H-NMR(DMSO-d6)δ値：2.75(2H,t,J=7.7Hz),2.93(2H,t,J=7.7Hz),3.07(3H,s),3.15(3H,s),7.16-7.23(1H,m),7.25-7.33(4H,m),7.37-7.53(4H,m),7.58-7.65(3H,m),8.25(1H,s),9.15(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -3-phenylpropanamide
1 H-NMR (DMSO-d 6 ) δ value: 2.75 (2H, t, J = 7.7 Hz), 2.93 (2H, t, J = 7.7 Hz), 3.07 (3H, s), 3.15 (3H, s) , 7.16-7.23 (1H, m), 7.25-7.33 (4H, m), 7.37-7.53 (4H, m), 7.58-7.65 (3H, m), 8.25 (1H, s), 9.15 (1H, s) .
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンゾフラン−５−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.27(3H,s),7.12-7.16(1H,m),7.39-7.46(1H,m),7.48-7.56(2H,m),7.58(1H,dd,J=8.4,2.1Hz),7.68-7.82(4H,m),7.90(1H,dd,J=8.7,1.8Hz),8.15(1H,d,J=2.2Hz),8.27(1H,d,J=1.4Hz),8.34-8.40(1H,m),9.64(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzofuran-5-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.27 (3H, s), 7.12-7.16 (1H, m), 7.39-7.46 (1H, m), 7.48-7.56 (2H , m), 7.58 (1H, dd, J = 8.4, 2.1Hz), 7.68-7.82 (4H, m), 7.90 (1H, dd, J = 8.7, 1.8Hz), 8.15 (1H, d, J = 2.2) Hz), 8.27 (1H, d, J = 1.4Hz), 8.34-8.40 (1H, m), 9.64 (1H, s).
３−フルオロ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.25(3H,s),7.39-7.55(4H,m),7.58-7.80(7H,m),8.25(1H,d,J=2.2Hz),9.76(1H,s).3-Fluoro-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.25 (3H, s), 7.39-7.55 (4H, m), 7.58-7.80 (7H, m), 8.25 (1H, d , J = 2.2Hz), 9.76 (1H, s).
４−フルオロ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.25(3H,s),7.38-7.46(3H,m),7.48-7.55(2H,m),7.58(1H,dd,J=8.3,2.2Hz),7.66-7.75(3H,m),7.95-8.03(2H,m),8.28(1H,d,J=2.2Hz),9.66(1H,s).4-Fluoro-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.25 (3H, s), 7.38-7.46 (3H, m), 7.48-7.55 (2H, m), 7.58 (1H, dd , J = 8.3, 2.2 Hz), 7.66-7.75 (3 H, m), 7.95-8.03 (2 H, m), 8.28 (1 H, d, J = 2.2 Hz), 9.66 (1 H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２−（トリフルオロメチル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.20(3H,s),7.39-7.46(1H,m),7.49-7.56(2H,m),7.58(1H,dd,J=8.3,1.8Hz),7.63-7.90(7H,m),8.18(1H,d,J=1.8Hz),9.97(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2- (trifluoromethyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.20 (3H, s), 7.39-7.46 (1H, m), 7.49-7.56 (2H, m), 7.58 (1H, dd , J = 8.3, 1.8Hz), 7.63-7.90 (7H, m), 8.18 (1H, d, J = 1.8Hz), 9.97 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−３−（トリフルオロメチル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.24(3H,s),7.39-7.46(1H,m),7.48-7.55(2H,m),7.62(1H,dd,J=8.3,2.2Hz),7.67-7.75(3H,m),7.80-7.86(1H,m),7.97-8.03(1H,m),8.17-8.27(3H,m),9.99(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -3- (trifluoromethyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.24 (3H, s), 7.39-7.46 (1H, m), 7.48-7.55 (2H, m), 7.62 (1H, dd , J = 8.3,2.2Hz), 7.67-7.75 (3H, m), 7.80-7.86 (1H, m), 7.97-8.03 (1H, m), 8.17-8.27 (3H, m), 9.99 (1H, s ).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−４−（トリフルオロメチル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.24(3H,s),7.39-7.46(1H,m),7.48-7.55(2H,m),7.61(1H,dd,J=8.3,2.1Hz),7.67-7.76(3H,m),7.96(2H,d,J=8.2Hz),8.12(2H,d,J=8.2Hz),8.23(1H,d,J=2.1Hz),9.92(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -4- (trifluoromethyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.24 (3H, s), 7.39-7.46 (1H, m), 7.48-7.55 (2H, m), 7.61 (1H, dd , J = 8.3,2.1Hz), 7.67-7.76 (3H, m), 7.96 (2H, d, J = 8.2Hz), 8.12 (2H, d, J = 8.2Hz), 8.23 (1H, d, J = 2.1Hz), 9.92 (1H, s).
２，４−ジメトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.17(3H,s),3.29(3H,s),3.87(3H,s),4.11(3H,s),6.74(1H,dd,J=8.7,2.3Hz),6.77(1H,d,J=2.3Hz),7.39-7.46(1H,m),7.47(1H,dd,J=8.3,2.2Hz),7.48-7.55(2H,m),7.65-7.71(2H,m),7.72(1H,d,J=8.3Hz),8.09(1H,d,J=8.7Hz),8.90(1H,d,J=2.2Hz),10.71(1H,s).2,4-Dimethoxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 3.29 (3H, s), 3.87 (3H, s), 4.11 (3H, s), 6.74 (1H, dd, J = 8.7 , 2.3Hz), 6.77 (1H, d, J = 2.3Hz), 7.39-7.46 (1H, m), 7.47 (1H, dd, J = 8.3, 2.2Hz), 7.48-7.55 (2H, m), 7.65 -7.71 (2H, m), 7.72 (1H, d, J = 8.3Hz), 8.09 (1H, d, J = 8.7Hz), 8.90 (1H, d, J = 2.2Hz), 10.71 (1H, s) .
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−ベンゾ［１，３］ジオキソール−５−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.25(3H,s),6.15(2H,s),7.10(1H,d,J=8.1Hz),7.38-7.45(2H,m),7.47-7.54(3H,m),7.56(1H,dd,J=8.3,2.2Hz),7.66-7.74(3H,m),8.33(1H,d,J=2.2Hz),9.44(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -benzo [1,3] dioxole-5-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.25 (3H, s), 6.15 (2H, s), 7.10 (1H, d, J = 8.1 Hz), 7.38-7.45 ( 2H, m), 7.47-7.54 (3H, m), 7.56 (1H, dd, J = 8.3,2.2Hz), 7.66-7.74 (3H, m), 8.33 (1H, d, J = 2.2Hz), 9.44 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２，３−ジヒドロベンゾ［１，４］ジオキシン−６−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),4.28-4.36(4H,m),7.00-7.06(1H,m),7.39-7.46(3H,m),7.48-7.58(3H,m),7.65-7.74(3H,m),8.37(1H,d,J=2.0Hz),9.41(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2,3-dihydrobenzo [1,4] dioxin-6-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 4.28-4.36 (4H, m), 7.00-7.06 (1H, m), 7.39-7.46 (3H , m), 7.48-7.58 (3H, m), 7.65-7.74 (3H, m), 8.37 (1H, d, J = 2.0Hz), 9.41 (1H, s).
２−エトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：1.42(3H,t,J=6.8Hz),3.14(3H,s),3.29(3H,s),4.54(2H,q,J=6.8Hz),7.09-7.17(1H,m),7.30(1H,d,J=8.3Hz),7.39-7.46(1H,m),7.47-7.62(4H,m),7.65-7.72(2H,m),7.75(1H,d,J=8.3Hz),8.09-8.15(1H,m),8.85(1H,d,J=2.0Hz),10.67(1H,s).2-Ethoxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 1.42 (3H, t, J = 6.8 Hz), 3.14 (3H, s), 3.29 (3H, s), 4.54 (2H, q, J = 6.8 Hz) , 7.09-7.17 (1H, m), 7.30 (1H, d, J = 8.3Hz), 7.39-7.46 (1H, m), 7.47-7.62 (4H, m), 7.65-7.72 (2H, m), 7.75 (1H, d, J = 8.3Hz), 8.09-8.15 (1H, m), 8.85 (1H, d, J = 2.0Hz), 10.67 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２−（トリフルオロメトキシ）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.21(3H,s),7.40-7.46(1H,m),7.49-7.61(5H,m),7.64-7.71(3H,m),7.73(1H,d,J=8.3Hz),7.85(1H,dd,J=7.4,1.4Hz),8.30-8.38(1H,m),9.76(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2- (trifluoromethoxy) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.21 (3H, s), 7.40-7.46 (1H, m), 7.49-7.61 (5H, m), 7.64-7.71 (3H , m), 7.73 (1H, d, J = 8.3Hz), 7.85 (1H, dd, J = 7.4, 1.4Hz), 8.30-8.38 (1H, m), 9.76 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）チオフェン−３−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),7.38-7.45(1H,m),7.47-7.59(4H,m),7.66-7.75(4H,m),8.27(1H,dd,J=2.9,1.5Hz),8.29(1H,d,J=2.2Hz),9.41(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) thiophene-3-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 7.38-7.45 (1H, m), 7.47-7.59 (4H, m), 7.66-7.75 (4H , m), 8.27 (1H, dd, J = 2.9, 1.5Hz), 8.29 (1H, d, J = 2.2Hz), 9.41 (1H, s).
実施例１２５
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.24(3H,s),6.86-6.90(1H,m),7.38-7.44(1H,m),7.47-7.54(2H,m),7.57(1H,dd,J=8.3,2.2Hz),7.65-7.72(3H,m),7.83-7.87(1H,m),8.20(1H,d,J=2.2Hz),8.35(1H,s),9.29(1H,s).Example 125
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.24 (3H, s), 6.86-6.90 (1H, m), 7.38-7.44 (1H, m), 7.47-7.54 (2H , m), 7.57 (1H, dd, J = 8.3,2.2Hz), 7.65-7.72 (3H, m), 7.83-7.87 (1H, m), 8.20 (1H, d, J = 2.2Hz), 8.35 ( 1H, s), 9.29 (1H, s).
実施例１２６〜１５４
実施例１２５と同様にして、表１９に示す化合物を得た。Examples 126-154
In the same manner as in Example 125, the compounds shown in Table 19 were obtained.
２−（２−メトキシフェニル）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）アセトアミド
1H-NMR(DMSO-d6)δ値：3.04(3H,s),3.11(3H,s),3.71(2H,s),3.74(3H,s),6.86-6.93(2H,m),7.25-7.32(2H,m),7.36-7.52(4H,m),7.58-7.65(3H,m),8.31(1H,s),9.08(1H,s).2- (2-Methoxyphenyl) -N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) acetamide
1 H-NMR (DMSO-d 6 ) δ value: 3.04 (3H, s), 3.11 (3H, s), 3.71 (2H, s), 3.74 (3H, s), 6.86-6.93 (2H, m), 7.25-7.32 (2H, m), 7.36-7.52 (4H, m), 7.58-7.65 (3H, m), 8.31 (1H, s), 9.08 (1H, s).
２−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.18(3H,s),3.30(3H,s),4.11(3H,s),7.16(1H,t,J=7.6Hz),7.29(1H,d,J=8.5Hz),7.39-7.55(4H,m),7.59-7.65(1H,m),7.66-7.71(2H,m),7.74(1H,d,J=8.3Hz),8.15(1H,dd,J=7.8,1.7Hz),8.90(1H,d,J=2.2Hz),10.83(1H,s).2-methoxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.18 (3H, s), 3.30 (3H, s), 4.11 (3H, s), 7.16 (1H, t, J = 7.6 Hz), 7.29 (1H, d, J = 8.5Hz), 7.39-7.55 (4H, m), 7.59-7.65 (1H, m), 7.66-7.71 (2H, m), 7.74 (1H, d, J = 8.3Hz), 8.15 (1H , dd, J = 7.8,1.7Hz), 8.90 (1H, d, J = 2.2Hz), 10.83 (1H, s).
３−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.26(3H,s),3.84(3H,s),7.17-7.23(1H,m),7.39-7.45(1H,m),7.46-7.54(5H,m),7.57(1H,dd,J=8.3,2.2Hz),7.66-7.75(3H,m),8.39(1H,d,J=2.2Hz),9.58(1H,s).3-methoxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.26 (3H, s), 3.84 (3H, s), 7.17-7.23 (1H, m), 7.39-7.45 (1H, m ), 7.46-7.54 (5H, m), 7.57 (1H, dd, J = 8.3,2.2Hz), 7.66-7.75 (3H, m), 8.39 (1H, d, J = 2.2Hz), 9.58 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−１Ｈ−ピロール−２−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.13(3H,s),3.26(3H,s),6.20-6.24(1H,m),6.76-6.82(1H,m),7.01-7.05(1H,m),7.38-7.45(1H,m),7.47-7.54(3H,m),7.64-7.72(3H,m),8.39(1H,d,J=2.2Hz),9.05(1H,s),11.83(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -1H-pyrrole-2-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.13 (3H, s), 3.26 (3H, s), 6.20-6.24 (1H, m), 6.76-6.82 (1H, m), 7.01-7.05 (1H , m), 7.38-7.45 (1H, m), 7.47-7.54 (3H, m), 7.64-7.72 (3H, m), 8.39 (1H, d, J = 2.2Hz), 9.05 (1H, s), 11.83 (1H, s).
１−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−１Ｈ−ピロール−２−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.14(3H,s),3.25(3H,s),3.90(3H,s),6.15(1H,dd,J=3.9,2.6Hz),6.80(1H,dd,J=3.9,1.6Hz),7.05-7.10(1H,m),7.39-7.45(1H,m),7.47-7.54(3H,m),7.64-7.73(3H,m),8.45(1H,d,J=2.2Hz),9.03(1H,s).1-methyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -1H-pyrrole-2-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.14 (3H, s), 3.25 (3H, s), 3.90 (3H, s), 6.15 (1H, dd, J = 3.9, 2.6 Hz), 6.80 ( 1H, dd, J = 3.9,1.6Hz), 7.05-7.10 (1H, m), 7.39-7.45 (1H, m), 7.47-7.54 (3H, m), 7.64-7.73 (3H, m), 8.45 ( 1H, d, J = 2.2Hz), 9.03 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）チアゾール−２−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.17(3H,s),3.28(3H,s),7.40-7.47(1H,m),7.49-7.56(2H,m),7.58(1H,dd,J=8.4,2.1Hz),7.66-7.73(2H,m),7.78(1H,d,J=8.4Hz),8.17(1H,d,J=3.2Hz),8.21(1H,d,J=3.2Hz),8.62(1H,d,J=2.1Hz),10.10(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) thiazole-2-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 3.28 (3H, s), 7.40-7.47 (1H, m), 7.49-7.56 (2H, m), 7.58 (1H, dd , J = 8.4,2.1Hz), 7.66-7.73 (2H, m), 7.78 (1H, d, J = 8.4Hz), 8.17 (1H, d, J = 3.2Hz), 8.21 (1H, d, J = 3.2Hz), 8.62 (1H, d, J = 2.1Hz), 10.10 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）チアゾール−５−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.08(3H,s),3.24(3H,s),7.38-7.45(1H,m),7.47-7.54(2H,m),7.62(1H,dd,J=8.3,2.2Hz),7.66-7.73(3H,m),8.09(1H,d,J=2.2Hz),8.59(1H,s),9.34(1H,s),9.90(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) thiazole-5-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.08 (3H, s), 3.24 (3H, s), 7.38-7.45 (1H, m), 7.47-7.54 (2H, m), 7.62 (1H, dd , J = 8.3,2.2Hz), 7.66-7.73 (3H, m), 8.09 (1H, d, J = 2.2Hz), 8.59 (1H, s), 9.34 (1H, s), 9.90 (1H, s) .
（Ｅ）−３−（２−メトキシフェニル）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）アクリルアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.23(3H,s),3.88(3H,s),7.03(1H,t,J=7.4Hz),7.08-7.18(2H,m),7.38-7.45(2H,m),7.47-7.54(3H,m),7.62-7.72(4H,m),7.89(1H,d,J=15.8Hz),8.49-8.54(1H,m),9.34(1H,s).(E) -3- (2-methoxyphenyl) -N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) acrylamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.23 (3H, s), 3.88 (3H, s), 7.03 (1H, t, J = 7.4 Hz), 7.08-7.18 ( 2H, m), 7.38-7.45 (2H, m), 7.47-7.54 (3H, m), 7.62-7.72 (4H, m), 7.89 (1H, d, J = 15.8Hz), 8.49-8.54 (1H, m), 9.34 (1H, s).
（Ｅ）−３−フェニル−２−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）アクリルアミド
1H-NMR(DMSO-d6)δ値：2.15-2.19(3H,m),3.14(3H,s),3.26(3H,s),7.34-7.56(10H,m),7.66-7.74(3H,m),8.43(1H,d,J=2.0Hz),9.19(1H,s).(E) -3-Phenyl-2-methyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) acrylamide
1 H-NMR (DMSO-d 6 ) δ value: 2.15-2.19 (3H, m), 3.14 (3H, s), 3.26 (3H, s), 7.34-7.56 (10H, m), 7.66-7.74 (3H , m), 8.43 (1H, d, J = 2.0Hz), 9.19 (1H, s).
２−（Ｎ−エチル−Ｎ−メチル）アミノ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：0.89(3H,t,J=7.1Hz),2.79(3H,s),3.12-3.21(2H,m),3.14(3H,s),3.28(3H,s),7.29-7.36(1H,m),7.39-7.63(6H,m),7.66-7.71(2H,m),7.73(1H,d,J=8.3Hz),8.16(1H,dd,J=7.9,1.6Hz),8.94(1H,d,J=2.2Hz),12.91(1H,s).2- (N-ethyl-N-methyl) amino-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 0.89 (3H, t, J = 7.1 Hz), 2.79 (3H, s), 3.12-3.21 (2H, m), 3.14 (3H, s), 3.28 ( 3H, s), 7.29-7.36 (1H, m), 7.39-7.63 (6H, m), 7.66-7.71 (2H, m), 7.73 (1H, d, J = 8.3Hz), 8.16 (1H, dd, J = 7.9,1.6Hz), 8.94 (1H, d, J = 2.2Hz), 12.91 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２−フェニルプロパンアミド
1H-NMR(DMSO-d6)δ値：1.47(3H,d,J=7.0Hz),3.00(3H,s),3.06(3H,s),4.04(1H,q,J=7.0Hz),7.23-7.29(1H,m),7.31-7.52(8H,m),7.56-7.65(3H,m),8.26(1H,s),9.05(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2-phenylpropanamide
1 H-NMR (DMSO-d 6 ) δ value: 1.47 (3H, d, J = 7.0 Hz), 3.00 (3H, s), 3.06 (3H, s), 4.04 (1H, q, J = 7.0 Hz) , 7.23-7.29 (1H, m), 7.31-7.52 (8H, m), 7.56-7.65 (3H, m), 8.26 (1H, s), 9.05 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−３−フェニルプロピオルアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.22(3H,s),7.38-7.45(1H,m),7.45-7.62(6H,m),7.62-7.72(5H,m),8.08(1H,s),10.15(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -3-phenylpropioramide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.22 (3H, s), 7.38-7.45 (1H, m), 7.45-7.62 (6H, m), 7.62-7.72 (5H , m), 8.08 (1H, s), 10.15 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２，３−ジヒドロベンゾフラン−７−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.18(3H,s),3.24-3.37(2H,m),3.27(3H,s),4.78-4.87(2H,m),7.04(1H,t,J=7.6Hz),7.40-7.56(5H,m),7.66-7.74(3H,m),7.80(1H,d,J=7.6Hz),8.92(1H,d,J=1.9Hz),10.66(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2,3-dihydrobenzofuran-7-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.18 (3H, s), 3.24 to 3.37 (2H, m), 3.27 (3H, s), 4.78-4.87 (2H, m), 7.04 (1H, t , J = 7.6Hz), 7.40-7.56 (5H, m), 7.66-7.74 (3H, m), 7.80 (1H, d, J = 7.6Hz), 8.92 (1H, d, J = 1.9Hz), 10.66 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−１Ｈ−インドール−７−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.15(3H,s),3.30(3H,s),6.54-6.58(1H,m),7.19(1H,t,J=7.6Hz),7.38-7.46(2H,m),7.49-7.57(2H,m),7.58(1H,dd,J=8.3,2.2Hz),7.66-7.78(4H,m),7.85(1H,d,J=7.8Hz),8.56(1H,d,J=2.2Hz),9.62(1H,s),11.30(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -1H-indole-7-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.15 (3H, s), 3.30 (3H, s), 6.54-6.58 (1H, m), 7.19 (1H, t, J = 7.6 Hz), 7.38- 7.46 (2H, m), 7.49-7.57 (2H, m), 7.58 (1H, dd, J = 8.3,2.2Hz), 7.66-7.78 (4H, m), 7.85 (1H, d, J = 7.8Hz) 8.56 (1H, d, J = 2.2Hz), 9.62 (1H, s), 11.30 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−１Ｈ−インドール−２−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.13(3H,s),3.29(3H,s),7.06-7.13(1H,m),7.17-7.29(2H,m),7.40-7.46(1H,m),7.47-7.56(3H,m),7.57(1H,dd,J=8.3,2.1Hz),7.68-7.76(4H,m),8.35(1H,d,J=2.1Hz),9.54(1H,s),11.88(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -1H-indole-2-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.13 (3H, s), 3.29 (3H, s), 7.06-7.13 (1H, m), 7.17-7.29 (2H, m), 7.40-7.46 (1H , m), 7.47-7.56 (3H, m), 7.57 (1H, dd, J = 8.3,2.1Hz), 7.68-7.76 (4H, m), 8.35 (1H, d, J = 2.1Hz), 9.54 ( 1H, s), 11.88 (1H, s).
２−シクロプロピル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：0.69-0.75(2H,m),0.93-1.00(2H,m),2.30-2.39(1H,m),3.09(3H,s),3.22(3H,s),7.01(1H,d,J=7.6Hz),7.27(1H,t,J=7.5Hz),7.36-7.46(2H,m),7.48-7.58(4H,m),7.65-7.73(3H,m),8.36-8.44(1H,broad),9.51(1H,s).2-Cyclopropyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 0.69-0.75 (2H, m), 0.93-1.00 (2H, m), 2.30-2.39 (1H, m), 3.09 (3H, s), 3.22 (3H , s), 7.01 (1H, d, J = 7.6Hz), 7.27 (1H, t, J = 7.5Hz), 7.36-7.46 (2H, m), 7.48-7.58 (4H, m), 7.65-7.73 ( 3H, m), 8.36-8.44 (1H, broad), 9.51 (1H, s).
２−ブロモ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.21(3H,s),7.40-7.47(2H,m),7.48-7.56(3H,m),7.58(1H,dd,J=8.3,2.0Hz),7.61-7.72(4H,m),7.74(1H,dd,J=8.1,1.0Hz),8.23-8.28(1H,m),9.80(1H,s).2-Bromo-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.21 (3H, s), 7.40-7.47 (2H, m), 7.48-7.56 (3H, m), 7.58 (1H, dd , J = 8.3, 2.0Hz), 7.61-7.72 (4H, m), 7.74 (1H, dd, J = 8.1, 1.0Hz), 8.23-8.28 (1H, m), 9.80 (1H, s).
１−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−１Ｈ−インドール−２−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.14(3H,s),3.28(3H,s),4.05(3H,s),7.13-7.21(2H,m),7.31-7.47(2H,m),7.49-7.62(4H,m),7.68-7.77(4H,m),8.42(1H,d,J=2.2Hz),9.56(1H,s).1-methyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -1H-indole-2-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.14 (3H, s), 3.28 (3H, s), 4.05 (3H, s), 7.13-7.21 (2H, m), 7.31-7.47 (2H, m ), 7.49-7.62 (4H, m), 7.68-7.77 (4H, m), 8.42 (1H, d, J = 2.2Hz), 9.56 (1H, s).
２−（ジフルオロメトキシ）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.24(3H,s),7.30(1H,t,J=73.0Hz),7.36-7.58(6H,m),7.62-7.72(3H,m),7.73(1H,d,J=8.3Hz),7.92(1H,dd,J=7.8,1.5Hz),8.53-8.59(1H,m),9.81(1H,s).2- (Difluoromethoxy) -N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.24 (3H, s), 7.30 (1H, t, J = 73.0 Hz), 7.36-7.58 (6H, m), 7.62 7.72 (3H, m), 7.73 (1H, d, J = 8.3Hz), 7.92 (1H, dd, J = 7.8,1.5Hz), 8.53-8.59 (1H, m), 9.81 (1H, s).
２−イソプロポキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：1.45(6H,d,J=5.8Hz),3.08(3H,s),3.29(3H,s),4.85-4.96(1H,m),7.07-7.14(1H,m),7.28(1H,d,J=8.3Hz),7.39-7.46(1H,m),7.48-7.60(4H,m),7.66-7.71(2H,m),7.75(1H,d,J=8.5Hz),8.03(1H,dd,J=7.9,1.8Hz),8.74(1H,d,J=2.2Hz),10.13(1H,s).2-Isopropoxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 1.45 (6H, d, J = 5.8 Hz), 3.08 (3H, s), 3.29 (3H, s), 4.85-4.96 (1H, m), 7.07- 7.14 (1H, m), 7.28 (1H, d, J = 8.3Hz), 7.39-7.46 (1H, m), 7.48-7.60 (4H, m), 7.66-7.71 (2H, m), 7.75 (1H, d, J = 8.5Hz), 8.03 (1H, dd, J = 7.9,1.8Hz), 8.74 (1H, d, J = 2.2Hz), 10.13 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２−（ピロリジン−１−イル）ベンズアミド
1H-NMR(DMSO-d6)δ値：1.85-1.93(4H,m),3.10(3H,s),3.20-3.28(4H,m),3.22(3H,s),6.80-6.87(1H,m),6.95(1H,d,J=8.3Hz),7.31-7.38(1H,m),7.39-7.61(5H,m),7.64-7.73(3H,m),8.63(1H,d,J=1.9Hz),9.78(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2- (pyrrolidin-1-yl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 1.85-1.93 (4H, m), 3.10 (3H, s), 3.20-3.28 (4H, m), 3.22 (3H, s), 6.80-6.87 (1H , m), 6.95 (1H, d, J = 8.3Hz), 7.31-7.38 (1H, m), 7.39-7.61 (5H, m), 7.64-7.73 (3H, m), 8.63 (1H, d, J = 1.9Hz), 9.78 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−１Ｈ−ピラゾール−４−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.24(3H,s),7.38-7.44(1H,m),7.47-7.56(3H,m),7.65-7.71(3H,m),7.85-8.10(1H,broad),8.20-8.40(1H,broad),8.27(1H,d,J=2.0Hz),9.16(1H,s),13.30-13.45(1H,broad).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -1H-pyrazole-4-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.24 (3H, s), 7.38-7.44 (1H, m), 7.47-7.56 (3H, m), 7.65-7.71 (3H , m), 7.85-8.10 (1H, broad), 8.20-8.40 (1H, broad), 8.27 (1H, d, J = 2.0Hz), 9.16 (1H, s), 13.30-13.45 (1H, broad).
３−（ジメチルアミノ）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.97(6H,s),3.14(3H,s),3.26(3H,s),6.96(1H,dd,J=8.3,2.7Hz),7.16(1H,d,J=7.8Hz),7.19-7.25(1H,m),7.36(1H,t,J=7.9Hz),7.39-7.46(1H,m),7.48-7.58(3H,m),7.66-7.73(2H,m),7.74(1H,d,J=8.3Hz),8.51(1H,d,J=2.2Hz),9.44(1H,s).3- (Dimethylamino) -N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.97 (6H, s), 3.14 (3H, s), 3.26 (3H, s), 6.96 (1H, dd, J = 8.3, 2.7 Hz), 7.16 ( 1H, d, J = 7.8Hz), 7.19-7.25 (1H, m), 7.36 (1H, t, J = 7.9Hz), 7.39-7.46 (1H, m), 7.48-7.58 (3H, m), 7.66 -7.73 (2H, m), 7.74 (1H, d, J = 8.3Hz), 8.51 (1H, d, J = 2.2Hz), 9.44 (1H, s).
４−（ジメチルアミノ）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.02(6H,s),3.14(3H,s),3.26(3H,s),6.81(2H,d,J=8.9Hz),7.38-7.45(1H,m),7.48-7.54(3H,m),7.65-7.73(3H,m),7.77(2H,d,J=8.9Hz),8.51(1H,d,J=2.2Hz),9.21(1H,s).4- (Dimethylamino) -N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.02 (6H, s), 3.14 (3H, s), 3.26 (3H, s), 6.81 (2H, d, J = 8.9 Hz), 7.38-7.45 ( 1H, m), 7.48-7.54 (3H, m), 7.65-7.73 (3H, m), 7.77 (2H, d, J = 8.9Hz), 8.51 (1H, d, J = 2.2Hz), 9.21 (1H , s).
２−（ジエチルアミノ）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：0.85(6H,t,J=6.9Hz),3.12-3.23(4H,m),3.15(3H,s),3.27(3H,s),7.33-7.56(6H,m),7.59-7.65(1H,m),7.66-7.71(2H,m),7.73(1H,d,J=8.0Hz),8.23(1H,dd,J=7.8,1.4Hz),8.93(1H,d,J=2.2Hz),13.16(1H,s).2- (Diethylamino) -N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 0.85 (6H, t, J = 6.9 Hz), 3.12-3.23 (4H, m), 3.15 (3H, s), 3.27 (3H, s), 7.33 7.56 (6H, m), 7.59-7.65 (1H, m), 7.66-7.71 (2H, m), 7.73 (1H, d, J = 8.0Hz), 8.23 (1H, dd, J = 7.8,1.4Hz) , 8.93 (1H, d, J = 2.2Hz), 13.16 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−１−フェニルシクロプロパン−１−カルボキサミド
1H-NMR(DMSO-d6)δ値：1.15-1.24(2H,m),1.50-1.58(2H,m),2.90(6H,s),7.34-7.64(12H,m),8.27(1H,s),8.54(1H,d,J=2.2Hz).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -1-phenylcyclopropane-1-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 1.15-1.24 (2H, m), 1.50-1.58 (2H, m), 2.90 (6H, s), 7.34-7.64 (12H, m), 8.27 (1H , s), 8.54 (1H, d, J = 2.2Hz).
４−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）チオフェン−３−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.17(3H,s),3.27(3H,s),4.04(3H,s),6.91(1H,d,J=3.7Hz),7.39-7.56(4H,m),7.64-7.70(2H,m),7.72(1H,d,J=8.3Hz),8.29(1H,d,J=3.7Hz),8.87(1H,d,J=2.0Hz),10.31(1H,s).4-methoxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) thiophene-3-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 3.27 (3H, s), 4.04 (3H, s), 6.91 (1H, d, J = 3.7 Hz), 7.39-7.56 ( 4H, m), 7.64-7.70 (2H, m), 7.72 (1H, d, J = 8.3Hz), 8.29 (1H, d, J = 3.7Hz), 8.87 (1H, d, J = 2.0Hz), 10.31 (1H, s).
３−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ピリジン−２−カルボキサミド
1H-NMR(DMSO-d6)δ値：2.73(3H,s),3.20(3H,s),3.27(3H,s),7.41-7.46(1H,m),7.49-7.57(3H,m),7.59(1H,dd,J=7.8,4.6Hz),7.68-7.74(3H,m),7.87(1H,d,J=7.8Hz),8.53-8.59(1H,m),8.78(1H,d,J=2.2Hz),11.02(1H,s).3-Methyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) pyridine-2-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 2.73 (3H, s), 3.20 (3H, s), 3.27 (3H, s), 7.41-7.46 (1H, m), 7.49-7.57 (3H, m ), 7.59 (1H, dd, J = 7.8, 4.6Hz), 7.68-7.74 (3H, m), 7.87 (1H, d, J = 7.8Hz), 8.53-8.59 (1H, m), 8.78 (1H, d, J = 2.2Hz), 11.02 (1H, s).
３，４−ジメトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.14(3H,s),3.26(3H,s),3.84(3H,s),3.85(3H,s),7.15(1H,d,J=8.3Hz),7.39-7.45(1H,m),7.48-7.58(5H,m),7.66-7.72(2H,m),7.72(1H,d,J=8.3Hz),8.44(1H,d,J=2.2Hz),9.45(1H,s).3,4-dimethoxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.14 (3H, s), 3.26 (3H, s), 3.84 (3H, s), 3.85 (3H, s), 7.15 (1H, d, J = 8.3 Hz), 7.39-7.45 (1H, m), 7.48-7.58 (5H, m), 7.66-7.72 (2H, m), 7.72 (1H, d, J = 8.3Hz), 8.44 (1H, d, J = 2.2Hz), 9.45 (1H, s).
実施例１５５
1H-NMR(DMSO-d6)δ値：3.17(3H,s),3.29(3H,s),3.79(3H,s),4.06(3H,s),7.20(1H,dd,J=9.1,3.2Hz),7.25(1H,d,J=9.1Hz),7.39-7.46(1H,m),7.47-7.56(3H,m),7.64-7.72(3H,m),7.74(1H,d,J=8.3Hz),8.91(1H,d,J=1.9Hz),10.92(1H,s).Example 155
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 3.29 (3H, s), 3.79 (3H, s), 4.06 (3H, s), 7.20 (1H, dd, J = 9.1 , 3.2Hz), 7.25 (1H, d, J = 9.1Hz), 7.39-7.46 (1H, m), 7.47-7.56 (3H, m), 7.64-7.72 (3H, m), 7.74 (1H, d, J = 8.3Hz), 8.91 (1H, d, J = 1.9Hz), 10.92 (1H, s).
実施例１５６〜１７０
実施例１５５と同様にして、表２０に示す化合物を得た。Examples 156-170
In the same manner as in Example 155, the compounds shown in Table 20 were obtained.
２，３−ジメトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.17(3H,s),3.29(3H,s),3.90(3H,s),3.98(3H,s),7.26(1H,t,J=8.1Hz),7.34(1H,dd,J=8.3,1.7Hz),7.39-7.46(1H,m),7.48-7.56(3H,m),7.64(1H,dd,J=7.9,1.6Hz),7.66-7.71(2H,m),7.74(1H,d,J=8.3Hz),8.88(1H,d,J=2.2Hz),10.89(1H,s).2,3-dimethoxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 3.29 (3H, s), 3.90 (3H, s), 3.98 (3H, s), 7.26 (1H, t, J = 8.1 Hz), 7.34 (1H, dd, J = 8.3,1.7Hz), 7.39-7.46 (1H, m), 7.48-7.56 (3H, m), 7.64 (1H, dd, J = 7.9,1.6Hz), 7.66 -7.71 (2H, m), 7.74 (1H, d, J = 8.3Hz), 8.88 (1H, d, J = 2.2Hz), 10.89 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２−ニトロベンズアミド
1H-NMR(DMSO-d6)δ値：3.08(3H,s),3.20(3H,s),7.40-7.47(1H,m),7.49-7.56(2H,m),7.59(1H,dd,J=8.3,2.2Hz),7.64-7.72(3H,m),7.74-7.81(2H,m),7.87-7.94(1H,m),8.15-8.21(2H,m),10.21(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2-nitrobenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.08 (3H, s), 3.20 (3H, s), 7.40-7.47 (1H, m), 7.49-7.56 (2H, m), 7.59 (1H, dd , J = 8.3, 2.2Hz), 7.64-7.72 (3H, m), 7.74-7.81 (2H, m), 7.87-7.94 (1H, m), 8.15-8.21 (2H, m), 10.21 (1H, s ).
２−メトキシ−４−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(CDCl3)δ値：2.43(3H,s),3.03(3H,s),3.32(3H,s),4.15(3H,s),6.87(1H,s),6.93(1H,d,J=7.8Hz),7.33-7.47(5H,m),7.63-7.69(2H,m),8.21(1H,d,J=7.8Hz),8.97(1H,d,J=2.0Hz),10.75(1H,s).2-Methoxy-4-methyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (CDCl 3 ) δ value: 2.43 (3H, s), 3.03 (3H, s), 3.32 (3H, s), 4.15 (3H, s), 6.87 (1H, s), 6.93 (1H, d, J = 7.8Hz), 7.33-7.47 (5H, m), 7.63-7.69 (2H, m), 8.21 (1H, d, J = 7.8Hz), 8.97 (1H, d, J = 2.0Hz), 10.75 (1H, s).
２−メトキシ−５−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.32(3H,s),3.17(3H,s),3.29(3H,s),4.07(3H,s),7.18(1H,d,J=8.3Hz),7.38-7.56(5H,m),7.65-7.71(2H,m),7.73(1H,d,J=8.3Hz),7.94(1H,d,J=1.9Hz),8.89(1H,d,J=2.0Hz),10.83(1H,s).2-Methoxy-5-methyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.32 (3H, s), 3.17 (3H, s), 3.29 (3H, s), 4.07 (3H, s), 7.18 (1H, d, J = 8.3 Hz), 7.38-7.56 (5H, m), 7.65-7.71 (2H, m), 7.73 (1H, d, J = 8.3Hz), 7.94 (1H, d, J = 1.9Hz), 8.89 (1H, d , J = 2.0Hz), 10.83 (1H, s).
５−クロロ−２−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.17(3H,s),3.29(3H,s),4.12(3H,s),7.35(1H,d,J=8.8Hz),7.40-7.46(1H,m),7.49-7.56(3H,m),7.65-7.71(3H,m),7.75(1H,d,J=8.3Hz),8.07(1H,d,J=2.9Hz),8.84(1H,d,J=1.9Hz),10.78(1H,s).5-Chloro-2-methoxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 3.29 (3H, s), 4.12 (3H, s), 7.35 (1H, d, J = 8.8 Hz), 7.40-7.46 ( 1H, m), 7.49-7.56 (3H, m), 7.65-7.71 (3H, m), 7.75 (1H, d, J = 8.3Hz), 8.07 (1H, d, J = 2.9Hz), 8.84 (1H , d, J = 1.9Hz), 10.78 (1H, s).
４−クロロ−２−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.17(3H,s),3.29(3H,s),4.14(3H,s),7.24(1H,dd,J=8.5,1.8Hz),7.38-7.46(2H,m),7.48-7.55(3H,m),7.65-7.71(2H,m),7.75(1H,d,J=8.3Hz),8.13(1H,d,J=8.5Hz),8.85(1H,d,J=2.2Hz),10.70(1H,s).4-Chloro-2-methoxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 3.29 (3H, s), 4.14 (3H, s), 7.24 (1H, dd, J = 8.5, 1.8 Hz), 7.38- 7.46 (2H, m), 7.48-7.55 (3H, m), 7.65-7.71 (2H, m), 7.75 (1H, d, J = 8.3Hz), 8.13 (1H, d, J = 8.5Hz), 8.85 (1H, d, J = 2.2Hz), 10.70 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンゾ［１，３］ジオキソール−４−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.18(3H,s),3.25(3H,s),6.23(2H,s),7.05(1H,t,J=7.9Hz),7.18-7.24(1H,m),7.40-7.56(5H,m),7.66-7.72(2H,m),7.72(1H,d,J=8.3Hz),8.84(1H,d,J=1.9Hz),10.08(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzo [1,3] dioxole-4-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.18 (3H, s), 3.25 (3H, s), 6.23 (2H, s), 7.05 (1H, t, J = 7.9 Hz), 7.18-7.24 ( 1H, m), 7.40-7.56 (5H, m), 7.66-7.72 (2H, m), 7.72 (1H, d, J = 8.3Hz), 8.84 (1H, d, J = 1.9Hz), 10.08 (1H , s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２，３−ジヒドロベンゾ［１，４］ジオキシン−５−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.18(3H,s),3.28(3H,s),4.33-4.42(2H,m),4.53-4.63(2H,m),7.02(1H,t,J=7.8Hz),7.14(1H,dd,J=8.1,1.7Hz),7.39-7.56(4H,m),7.61-7.71(3H,m),7.73(1H,d,J=8.3Hz),8.86(1H,d,J=2.0Hz),10.70(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2,3-dihydrobenzo [1,4] dioxin-5-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.18 (3H, s), 3.28 (3H, s), 4.33-4.42 (2H, m), 4.53-4.63 (2H, m), 7.02 (1H, t , J = 7.8Hz), 7.14 (1H, dd, J = 8.1,1.7Hz), 7.39-7.56 (4H, m), 7.61-7.71 (3H, m), 7.73 (1H, d, J = 8.3Hz) , 8.86 (1H, d, J = 2.0Hz), 10.70 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ピラジン−２−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.18(3H,s),3.29(3H,s),7.41-7.47(1H,m),7.50-7.56(2H,m),7.58(1H,dd,J=8.3,1.9Hz),7.68-7.73(2H,m),7.77(1H,d,J=8.3Hz),8.75(1H,d,J=1.9Hz),8.84-8.88(1H,m),8.99(1H,d,J=2.4Hz),9.38(1H,d,J=1.5Hz),10.59(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) pyrazine-2-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.18 (3H, s), 3.29 (3H, s), 7.41-7.47 (1H, m), 7.50-7.56 (2H, m), 7.58 (1H, dd , J = 8.3,1.9Hz), 7.68-7.73 (2H, m), 7.77 (1H, d, J = 8.3Hz), 8.75 (1H, d, J = 1.9Hz), 8.84-8.88 (1H, m) , 8.99 (1H, d, J = 2.4Hz), 9.38 (1H, d, J = 1.5Hz), 10.59 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−５−（フェニル）ピリジン−３−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.26(3H,s),7.40-7.60(6H,m),7.62(1H,dd,J=8.0,2.0Hz),7.68-7.77(3H,m),7.81-7.88(2H,m),8.22-8.28(1H,m),8.50-8.55(1H,m),9.06(1H,d,J=2.0Hz),9.12(1H,d,J=2.0Hz),10.09(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -5- (phenyl) pyridine-3-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.26 (3H, s), 7.40-7.60 (6H, m), 7.62 (1H, dd, J = 8.0, 2.0 Hz), 7.68-7.77 (3H, m), 7.81-7.88 (2H, m), 8.22-8.28 (1H, m), 8.50-8.55 (1H, m), 9.06 (1H, d, J = 2.0Hz), 9.12 ( 1H, d, J = 2.0Hz), 10.09 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２−（フェニル）ピリジン−５−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.27(3H,s),7.40-7.46(1H,m),7.48-7.59(5H,m),7.61(1H,dd,J=8.3,2.0Hz),7.68-7.76(3H,m),8.16-8.24(3H,m),8.30(1H,d,J=2.0Hz),8.35(1H,dd,J=8.3,2.2Hz),9.18(1H,d,J=2.2Hz),9.94(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2- (phenyl) pyridine-5-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.27 (3H, s), 7.40-7.46 (1H, m), 7.48-7.59 (5H, m), 7.61 (1H, dd , J = 8.3,2.0Hz), 7.68-7.76 (3H, m), 8.16-8.24 (3H, m), 8.30 (1H, d, J = 2.0Hz), 8.35 (1H, dd, J = 8.3,2.2 Hz), 9.18 (1H, d, J = 2.2Hz), 9.94 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２−（フェニル）ピリジン−４−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.26(3H,s),7.40-7.46(1H,m),7.47-7.58(5H,m),7.64(1H,dd,J=8.3,2.2Hz),7.68-7.79(4H,m),8.15-8.21(2H,m),8.23(1H,d,J=1.7Hz),8.38(1H,s),8.90(1H,d,J=4.9Hz),10.14(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2- (phenyl) pyridine-4-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.26 (3H, s), 7.40-7.46 (1H, m), 7.47-7.58 (5H, m), 7.64 (1H, dd , J = 8.3,2.2Hz), 7.68-7.79 (4H, m), 8.15-8.21 (2H, m), 8.23 (1H, d, J = 1.7Hz), 8.38 (1H, s), 8.90 (1H, d, J = 4.9Hz), 10.14 (1H, s).
２−エチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：1.20(3H,t,J=7.5Hz),2.81(2H,q,J=7.5Hz),3.09(3H,s),3.22(3H,s),7.29-7.38(2H,m),7.39-7.48(2H,m),7.49-7.59(4H,m),7.65-7.73(3H,m),8.29-8.37(1H,broad),9.47(1H,s).2-Ethyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 1.20 (3H, t, J = 7.5 Hz), 2.81 (2H, q, J = 7.5 Hz), 3.09 (3H, s), 3.22 (3H, s) , 7.29-7.38 (2H, m), 7.39-7.48 (2H, m), 7.49-7.59 (4H, m), 7.65-7.73 (3H, m), 8.29-8.37 (1H, broad), 9.47 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２−（メチルチオ）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.46(3H,s),3.10(3H,s),3.23(3H,s),7.26-7.33(1H,m),7.39-7.48(2H,m),7.49-7.59(4H,m),7.64-7.71(3H,m),7.71(1H,d,J=8.3Hz),8.34(1H,s),9.59(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2- (methylthio) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.46 (3H, s), 3.10 (3H, s), 3.23 (3H, s), 7.26-7.33 (1H, m), 7.39-7.48 (2H, m ), 7.49-7.59 (4H, m), 7.64-7.71 (3H, m), 7.71 (1H, d, J = 8.3Hz), 8.34 (1H, s), 9.59 (1H, s).
２−（ジメチルアミノ）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.79(6H,s),3.14(3H,s),3.29(3H,s),7.25-7.32(1H,m),7.39-7.61(6H,m),7.65-7.72(2H,m),7.73(1H,d,J=8.3Hz),8.04-8.12(1H,m),8.95(1H,d,J=1.7Hz),12.60(1H,s).2- (Dimethylamino) -N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.79 (6H, s), 3.14 (3H, s), 3.29 (3H, s), 7.25-7.32 (1H, m), 7.39-7.61 (6H, m ), 7.65-7.72 (2H, m), 7.73 (1H, d, J = 8.3Hz), 8.04-8.12 (1H, m), 8.95 (1H, d, J = 1.7Hz), 12.60 (1H, s) .
実施例１７１
1H-NMR(DMSO-d6)δ値：3.14(3H,s),3.28(3H,s),3.88(3H,s),6.96(1H,d,J=3.0Hz),7.32(1H,t,J=7.8Hz),7.41-7.46(1H,m),7.50-7.57(4H,m),7.62(1H,d,J=7.3Hz),7.69-7.78(4H,m),8.68(1H,d,J=2.2Hz),9.39(1H,s).Example 171
1 H-NMR (DMSO-d 6 ) δ value: 3.14 (3H, s), 3.28 (3H, s), 3.88 (3H, s), 6.96 (1H, d, J = 3.0 Hz), 7.32 (1H, t, J = 7.8Hz), 7.41-7.46 (1H, m), 7.50-7.57 (4H, m), 7.62 (1H, d, J = 7.3Hz), 7.69-7.78 (4H, m), 8.68 (1H , d, J = 2.2 Hz), 9.39 (1H, s).
実施例１７２
1H-NMR(DMSO-d6)δ値：3.14(3H,s),3.28(3H,s),6.96-7.00(1H,m),7.25(1H,t,J=7.8Hz),7.43(1H,t,J=7.3Hz),7.50-7.61(5H,m),7.65-7.78(4H,m),8.69(1H,d,J=2.2Hz),9.38(1H,s),11.52(1H,s).Example 172
1 H-NMR (DMSO-d 6 ) δ value: 3.14 (3H, s), 3.28 (3H, s), 6.96-7.00 (1H, m), 7.25 (1H, t, J = 7.8 Hz), 7.43 ( 1H, t, J = 7.3Hz), 7.50-7.61 (5H, m), 7.65-7.78 (4H, m), 8.69 (1H, d, J = 2.2Hz), 9.38 (1H, s), 11.52 (1H , s).
実施例１７３，１７４
実施例１７２と同様にして、表２１に示す化合物を得た。Examples 173, 174
In the same manner as in Example 172, the compounds shown in Table 21 were obtained.
１−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−１Ｈ−インドール−７−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.23(3H,s),3.81(3H,s),6.55(1H,d,J=3.2Hz),7.12(1H,t,J=7.4Hz),7.37-7.46(3H,m),7.49-7.60(3H,m),7.67-7.76(4H,m),8.39(1H,s),9.76(1H,s).1-methyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -1H-indole-7-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.23 (3H, s), 3.81 (3H, s), 6.55 (1H, d, J = 3.2 Hz), 7.12 (1H, t, J = 7.4Hz), 7.37-7.46 (3H, m), 7.49-7.60 (3H, m), 7.67-7.76 (4H, m), 8.39 (1H, s), 9.76 (1H, s).
２−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ピリジン−３−カルボキサミド
1H-NMR(DMSO-d6)δ値：2.62(3H,s),3.08(3H,s),3.21(3H,s),7.37(1H,dd,J=7.6,4.9Hz),7.40-7.45(1H,s),7.50-7.55(2H,m),7.58(1H,dd,J=8.3,2.2Hz),7.67-7.73(3H,m),7.90(1H,dd,J=7.6,1.6Hz),8.24(1H,s),8.57(1H,dd,J=4.9,1.6Hz),9.85(1H,s).2-Methyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) pyridine-3-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 2.62 (3H, s), 3.08 (3H, s), 3.21 (3H, s), 7.37 (1H, dd, J = 7.6, 4.9 Hz), 7.40- 7.45 (1H, s), 7.50-7.55 (2H, m), 7.58 (1H, dd, J = 8.3,2.2Hz), 7.67-7.73 (3H, m), 7.90 (1H, dd, J = 7.6,1.6 Hz), 8.24 (1H, s), 8.57 (1H, dd, J = 4.9, 1.6Hz), 9.85 (1H, s).
実施例１７５
1H-NMR(DMSO-d6)δ値：3.19(3H,s),3.25(3H,s),7.38-7.55(4H,m),7.64-7.71(3H,m),7.82-7.88(2H,m),8.79(1H,d,J=2.2Hz),9.91(1H,s),12.72(1H,s).Example 175
1 H-NMR (DMSO-d 6 ) δ value: 3.19 (3H, s), 3.25 (3H, s), 7.38-7.55 (4H, m), 7.64-7.71 (3H, m), 7.82-7.88 (2H , m), 8.79 (1H, d, J = 2.2Hz), 9.91 (1H, s), 12.72 (1H, s).
実施例１７６
３−ヒドロキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ピリジン−２−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.18(3H,s),3.29(3H,s),7.41-7.47(1H,m),7.50-7.66(5H,m),7.68-7.74(2H,m),7.77(1H,d,J=8.3Hz),8.24-8.30(1H,m),8.62(1H,s),10.82(1H,s),11.74(1H,s).Example 176
3-hydroxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) pyridine-2-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.18 (3H, s), 3.29 (3H, s), 7.41-7.47 (1H, m), 7.50-7.66 (5H, m), 7.68-7.74 (2H , m), 7.77 (1H, d, J = 8.3Hz), 8.24-8.30 (1H, m), 8.62 (1H, s), 10.82 (1H, s), 11.74 (1H, s).
実施例１７７
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.20(3H,s),7.39-7.46(1H,m),7.48-7.72(9H,m),7.87(1H,d,J=7.3Hz),8.26(1H,s),9.60-9.85(1H,broad),13.00-13.20(1H,broad).Example 177
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.20 (3H, s), 7.39-7.46 (1H, m), 7.48-7.72 (9H, m), 7.87 (1H, d , J = 7.3Hz), 8.26 (1H, s), 9.60-9.85 (1H, broad), 13.00-13.20 (1H, broad).
実施例１７８
得られた２−（アセトキシ）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミドにメタノール0.50mL、ジオキサン1.0mLおよび2.0mol/L水酸化ナトリウム水溶液0.27mLを加え、室温で2時間攪拌した。反応混合物を1.0mol/L塩酸でpH2.0に調整し、酢酸エチルを加えた。有機層を分取し、飽和塩化ナトリウム水溶液で洗浄後、無水硫酸マグネシウムで乾燥させ、減圧下で溶媒を留去した。得られた残留物にジイソプロピルエーテルを加え、固形物をろ取し、白色固体の２−ヒドロキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド41mgを得た。
1H-NMR(DMSO-d6)δ値：3.17(3H,s),3.26(3H,s),6.99(1H,t,J=7.4Hz),7.11(1H,d,J=8.0Hz),7.39-7.55(5H,m),7.65-7.73(3H,m),8.01-8.08(1H,m),8.90(1H,d,J=2.0Hz),11.19(1H,s),11.69(1H,s).Example 178
To the obtained 2- (acetoxy) -N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide, 0.50 mL of methanol, 1.0 mL of dioxane and 0.27 mL of 2.0 mol / L sodium hydroxide aqueous solution were added. And stirred at room temperature for 2 hours. The reaction mixture was adjusted to pH 2.0 with 1.0 mol / L hydrochloric acid, and ethyl acetate was added. The organic layer was separated, washed with a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Diisopropyl ether was added to the obtained residue, and the solid was collected by filtration to obtain 41 mg of 2-hydroxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide as a white solid.
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 3.26 (3H, s), 6.99 (1H, t, J = 7.4 Hz), 7.11 (1H, d, J = 8.0 Hz) , 7.39-7.55 (5H, m), 7.65-7.73 (3H, m), 8.01-8.08 (1H, m), 8.90 (1H, d, J = 2.0Hz), 11.19 (1H, s), 11.69 (1H , s).
実施例１７９
得られた２−（アセトキシ）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミドにメタノール1.0mL、ジオキサン1.0mLおよび2.0mol/L水酸化ナトリウム水溶液0.22mLを加え、室温で1時間30分間攪拌した。反応混合物に1.0mol/L塩酸5.0mLおよび酢酸エチル5.0mLを加えた。有機層を分取し、飽和塩化ナトリウム水溶液で洗浄後、無水硫酸マグネシウムで乾燥させ、減圧下で溶媒を留去した。得られた残留物にジイソプロピルエーテルを加え、固形物をろ取し、白色固体の３−ヒドロキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド28mgを得た。
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.25(3H,s),6.98-7.04(1H,m),7.29-7.45(4H,m),7.48-7.55(2H,m),7.56(1H,dd,J=8.3,2.1Hz),7.66-7.72(2H,m),7.72(1H,d,J=8.3Hz),8.39(1H,d,J=2.1Hz),9.45(1H,s),9.87(1H,s).Example 179
To the obtained 2- (acetoxy) -N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide, 1.0 mL of methanol, 1.0 mL of dioxane and 0.22 mL of 2.0 mol / L sodium hydroxide aqueous solution were added. The mixture was stirred at room temperature for 1 hour and 30 minutes. To the reaction mixture, 1.0 mL / L hydrochloric acid (5.0 mL) and ethyl acetate (5.0 mL) were added. The organic layer was separated, washed with a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Diisopropyl ether was added to the obtained residue, and the solid substance was collected by filtration to obtain 28 mg of 3-hydroxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide as a white solid.
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.25 (3H, s), 6.98-7.04 (1H, m), 7.29-7.45 (4H, m), 7.48-7.55 (2H , m), 7.56 (1H, dd, J = 8.3,2.1Hz), 7.66-7.72 (2H, m), 7.72 (1H, d, J = 8.3Hz), 8.39 (1H, d, J = 2.1Hz) , 9.45 (1H, s), 9.87 (1H, s).
実施例１８０
４−ヒドロキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.25(3H,s),6.87-6.94(2H,m),7.38-7.45(1H,m),7.48-7.56(3H,m),7.65-7.73(3H,m),7.76-7.82(2H,m),8.42(1H,d,J=2.0Hz),9.32(1H,s),10.21(1H,s).Example 180
4-Hydroxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.25 (3H, s), 6.87-6.94 (2H, m), 7.38-7.45 (1H, m), 7.48-7.56 (3H , m), 7.65-7.73 (3H, m), 7.76-7.82 (2H, m), 8.42 (1H, d, J = 2.0Hz), 9.32 (1H, s), 10.21 (1H, s).
実施例１８１
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.25(3H,s),6.36-6.45(2H,broad),6.59-6.66(1H,m),6.80(1H,d,J=8.3Hz),7.20-7.27(1H,m),7.39-7.45(1H,m),7.48-7.60(4H,m),7.66-7.73(3H,m),8.40(1H,d,J=2.0Hz),9.39(1H,s).Example 181
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.25 (3H, s), 6.36-6.45 (2H, broad), 6.59-6.66 (1H, m), 6.80 (1H, d , J = 8.3Hz), 7.20-7.27 (1H, m), 7.39-7.45 (1H, m), 7.48-7.60 (4H, m), 7.66-7.73 (3H, m), 8.40 (1H, d, J = 2.0Hz), 9.39 (1H, s).
実施例１８２
1H-NMR(DMSO-d6)δ値：3.17(3H,s),3.21(3H,s),5.16(2H,s),7.14-7.23(2H,m),7.40-7.60(5H,m),7.66-7.76(3H,m),8.11-8.17(1H,m),8.88(1H,d,J=1.7Hz),10.79(1H,s).Example 182
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 3.21 (3H, s), 5.16 (2H, s), 7.14-7.23 (2H, m), 7.40-7.60 (5H, m ), 7.66-7.76 (3H, m), 8.11-8.17 (1H, m), 8.88 (1H, d, J = 1.7Hz), 10.79 (1H, s).
実施例１８３
得られた２−（２−（メチル（メチルスルホニル）アミノ）−５−（フェニル）フェニルカルバモイル）ベンジル＝ベンゾアートにメタノール0.50mL、ジオキサン0.50mLおよび2.0mol/L水酸化ナトリウム水溶液0.080mLを加え、室温で1時間30分間攪拌した。反応混合物に水を加え、1.0mol/L塩酸でpH7.0に調整後、酢酸エチルを加えた。有機層を分取し、飽和塩化ナトリウム水溶液で洗浄後、無水硫酸マグネシウムで乾燥させ、減圧下で溶媒を留去した。得られた残留物をシリカゲルカラムクロマトグラフィー［溶離液；100-25％ヘキサン／酢酸エチル］で精製し、白色固体の２−（ヒドロキシメチル）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド20mgを得た。
1H-NMR(DMSO-d6)δ値：3.08(3H,s),3.21(3H,s),4.71(2H,d,J=5.4Hz),5.40(1H,t,J=5.4Hz),7.38-7.46(2H,m),7.48-7.62(5H,m),7.63-7.73(4H,m),8.35-8.43(1H,m),9.77(1H,s).Example 183
To the obtained 2- (2- (methyl (methylsulfonyl) amino) -5- (phenyl) phenylcarbamoyl) benzyl benzoate, 0.50 mL of methanol, 0.50 mL of dioxane and 0.080 mL of 2.0 mol / L aqueous sodium hydroxide solution were added. The mixture was stirred at room temperature for 1 hour and 30 minutes. Water was added to the reaction mixture, pH was adjusted to 7.0 with 1.0 mol / L hydrochloric acid, and ethyl acetate was added. The organic layer was separated, washed with a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 100-25% hexane / ethyl acetate] to give 2- (hydroxymethyl) -N- (2- (methyl (methylsulfonyl) amino) as a white solid. 20 mg of -5-phenylphenyl) benzamide was obtained.
1 H-NMR (DMSO-d 6 ) δ value: 3.08 (3H, s), 3.21 (3H, s), 4.71 (2H, d, J = 5.4Hz), 5.40 (1H, t, J = 5.4Hz) 7.38-7.46 (2H, m), 7.48-7.62 (5H, m), 7.63-7.73 (4H, m), 8.35-8.43 (1H, m), 9.77 (1H, s).
実施例１８４
1H-NMR(DMSO-d6)δ値：3.08(3H,s),3.21(3H,s),5.33-5.37(1H,m),5.83-5.88(1H,m),7.12(1H,dd,J=17.4,11.1Hz),7.39-7.46(2H,m),7.48-7.74(7H,m),7.57(1H,dd,J=8.2,2.1Hz),7.76(1H,d,J=7.6Hz),8.32(1H,s),9.60(1H,s).Example 184
1 H-NMR (DMSO-d 6 ) δ value: 3.08 (3H, s), 3.21 (3H, s), 5.33-5.37 (1H, m), 5.83-5.88 (1H, m), 7.12 (1H, dd , J = 17.4,11.1Hz), 7.39-7.46 (2H, m), 7.48-7.74 (7H, m), 7.57 (1H, dd, J = 8.2,2.1Hz), 7.76 (1H, d, J = 7.6 Hz), 8.32 (1H, s), 9.60 (1H, s).
実施例１８５
1H-NMR(DMSO-d6)δ値：3.18(3H,s),3.26(3H,s),3.96(3H,s),7.40-7.46(1H,m),7.47-7.56(3H,m),7.63-7.73(4H,m),7.74-7.80(1H,m),8.29(1H,dd,J=4.5,1.1Hz),8.76(1H,d,J=2.0Hz),10.58(1H,s).Example 185
1 H-NMR (DMSO-d 6 ) δ value: 3.18 (3H, s), 3.26 (3H, s), 3.96 (3H, s), 7.40-7.46 (1H, m), 7.47-7.56 (3H, m ), 7.63-7.73 (4H, m), 7.74-7.80 (1H, m), 8.29 (1H, dd, J = 4.5,1.1Hz), 8.76 (1H, d, J = 2.0Hz), 10.58 (1H, s).
実施例１８６
1H-NMR(DMSO-d6)δ値：2.81(3H,d,J=5.1Hz),3.11(3H,s),3.25(3H,s),6.64-6.71(1H,m),6.74(1H,d,J=8.0Hz),7.33-7.45(3H,m),7.48-7.57(3H,m),7.64(1H,dd,J=8.0,1.3Hz),7.65-7.74(3H,m),8.37(1H,d,J=2.2Hz),9.45(1H,s).Example 186
1 H-NMR (DMSO-d 6 ) δ value: 2.81 (3H, d, J = 5.1 Hz), 3.11 (3H, s), 3.25 (3H, s), 6.64 to 6.71 (1H, m), 6.74 ( 1H, d, J = 8.0Hz), 7.33-7.45 (3H, m), 7.48-7.57 (3H, m), 7.64 (1H, dd, J = 8.0,1.3Hz), 7.65-7.74 (3H, m) 8.37 (1H, d, J = 2.2Hz), 9.45 (1H, s).
実施例１８７
1H-NMR(DMSO-d6)δ値：2.99(2H,t,J=8.7Hz),3.13(3H,s),3.26(3H,s),3.55-3.63(2H,m),6.58-6.65(2H,m),7.21(1H,d,J=7.1Hz),7.35-7.45(2H,m),7.48-7.54(3H,m),7.65-7.73(3H,m),8.55(1H,d,J=2.2Hz),9.39(1H,s).Example 187
1 H-NMR (DMSO-d 6 ) δ value: 2.99 (2H, t, J = 8.7 Hz), 3.13 (3H, s), 3.26 (3H, s), 3.55-3.63 (2H, m), 6.58- 6.65 (2H, m), 7.21 (1H, d, J = 7.1Hz), 7.35-7.45 (2H, m), 7.48-7.54 (3H, m), 7.65-7.73 (3H, m), 8.55 (1H, d, J = 2.2Hz), 9.39 (1H, s).
実施例１８８
得られた１−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−インドリン−７−カルボキサミド10mgの酢酸エチル1.0mL溶液に4.0mol/L塩化水素−ジオキサン溶液5.7μLを加え、室温で10分間攪拌後、固形物をろ取し、白色固体の１−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）インドリン−７−カルボキサミド塩酸塩6.8mgを得た。
1H-NMR(DMSO-d6)δ値：2.81(3H,s),3.04(2H,t,J=8.0Hz),3.11(3H,s),3.24(3H,s),3.49(2H,t,J=8.0Hz),6.88-6.97(1H,m),7.28-7.35(1H,m),7.39-7.56(5H,m),7.64-7.71(2H,m),7.71(1H,d,J=8.3Hz),8.52(1H,s),10.04(1H,s).Example 188
The resulting 1-methyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -indoline-7-carboxamide 10 mg in ethyl acetate 1.0 mL solution in 4.0 mol / L hydrogen chloride-dioxane solution 5.7 μL was added and the mixture was stirred at room temperature for 10 minutes, and then the solid was collected by filtration to give 1-methyl-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) indoline-7-carboxamide hydrochloride as a white solid. 6.8 mg of salt was obtained.
1 H-NMR (DMSO-d 6 ) δ value: 2.81 (3H, s), 3.04 (2H, t, J = 8.0 Hz), 3.11 (3H, s), 3.24 (3H, s), 3.49 (2H, t, J = 8.0Hz), 6.88-6.97 (1H, m), 7.28-7.35 (1H, m), 7.39-7.56 (5H, m), 7.64-7.71 (2H, m), 7.71 (1H, d, J = 8.3Hz), 8.52 (1H, s), 10.04 (1H, s).
実施例１８９
1H-NMR(DMSO-d6)δ値：3.08(3H,s),3.19(2H,t,J=7.3Hz),4.01(3H,s),4.13(2H,t,J=7.3Hz),7.09-7.15(1H,m),7.22-7.27(1H,m),7.37-7.43(1H,m),7.45-7.72(6H,m),8.02(1H,dd,J=7.8,1.7Hz),8.40(1H,d,J=1.7Hz),10.67(1H,s).Example 189
1 H-NMR (DMSO-d 6 ) δ value: 3.08 (3H, s), 3.19 (2H, t, J = 7.3 Hz), 4.01 (3H, s), 4.13 (2H, t, J = 7.3 Hz) , 7.09-7.15 (1H, m), 7.22-7.27 (1H, m), 7.37-7.43 (1H, m), 7.45-7.72 (6H, m), 8.02 (1H, dd, J = 7.8,1.7Hz) , 8.40 (1H, d, J = 1.7Hz), 10.67 (1H, s).
実施例１９０，１９１
実施例１８９と同様にして、表２２示す化合物を得た。Examples 190, 191
In the same manner as in Example 189, compounds shown in Table 22 were obtained.
４−メトキシ−Ｎ−（１−（メチルスルホニル）−５−フェニルインドリン−７−イル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.14(3H,s),3.20(2H,t,J=7.1Hz),3.85(3H,s),4.15(2H,t,J=7.1Hz),7.09-7.15(2H,m),7.37-7.43(1H,m),7.47-7.54(3H,m),7.64-7.70(2H,m),7.85-7.92(2H,m),8.32(1H,s),10.02(1H,s).4-Methoxy-N- (1- (methylsulfonyl) -5-phenylindoline-7-yl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.14 (3H, s), 3.20 (2H, t, J = 7.1 Hz), 3.85 (3H, s), 4.15 (2H, t, J = 7.1 Hz) , 7.09-7.15 (2H, m), 7.37-7.43 (1H, m), 7.47-7.54 (3H, m), 7.64-7.70 (2H, m), 7.85-7.92 (2H, m), 8.32 (1H, s), 10.02 (1H, s).
Ｎ−（１−（メチルスルホニル）−５−フェニルインドリン−７−イル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.14(3H,s),3.21(2H,t,J=7.5Hz),4.15(2H,t,J=7.5Hz),7.38-7.43(1H,m),7.47-7.70(8H,m),7.90-7.95(2H,m),8.32(1H,d,J=1.7Hz),10.12(1H,s).N- (1- (methylsulfonyl) -5-phenylindoline-7-yl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.14 (3H, s), 3.21 (2H, t, J = 7.5 Hz), 4.15 (2H, t, J = 7.5 Hz), 7.38-7.43 (1H, m), 7.47-7.70 (8H, m), 7.90-7.95 (2H, m), 8.32 (1H, d, J = 1.7Hz), 10.12 (1H, s).
実施例１９２
Ｎ−（１−（エチルスルホニル）−５−フェニルインドリン−７−イル）ベンズアミド
1H-NMR(CDCl3)δ値：1.40(3H,t,J=7.4Hz),3.07(2H,q,J=7.4Hz),3.17(2H,t,J=7.6Hz),4.19(2H,t,J=7.6Hz),7.30-7.39(2H,m),7.40-7.58(5H,m),7.62-7.67(2H,m),8.02-8.07(2H,m),8.54(1H,s),10.11(1H,s).Example 192
N- (1- (ethylsulfonyl) -5-phenylindoline-7-yl) benzamide
1 H-NMR (CDCl 3 ) δ value: 1.40 (3H, t, J = 7.4 Hz), 3.07 (2H, q, J = 7.4 Hz), 3.17 (2H, t, J = 7.6 Hz), 4.19 (2H , t, J = 7.6Hz), 7.30-7.39 (2H, m), 7.40-7.58 (5H, m), 7.62-7.67 (2H, m), 8.02-8.07 (2H, m), 8.54 (1H, s ), 10.11 (1H, s).
実施例１９３，１９４
実施例１８９と同様にして、表２３示す化合物を得た。Examples 193, 194
In the same manner as in Example 189, compounds shown in Table 23 were obtained.
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルピリジン−３−イル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.14(3H,s),3.25(3H,s),7.45-7.68(6H,m),7.74-7.80(2H,m),7.92-7.98(2H,m),8.66(1H,d,J=2.4Hz),8.71(1H,d,J=2.4Hz),9.80(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylpyridin-3-yl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.14 (3H, s), 3.25 (3H, s), 7.45-7.68 (6H, m), 7.74-7.80 (2H, m), 7.92-7.98 (2H , m), 8.66 (1H, d, J = 2.4Hz), 8.71 (1H, d, J = 2.4Hz), 9.80 (1H, s).
２−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルピリジン−３−イル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.27(3H,s),3.28(3H,s),4.15(3H,s),7.19(1H,t,J=7.6Hz),7.32(1H,d,J=8.3Hz),7.46-7.52(1H,m),7.53-7.60(2H,m),7.62-7.69(1H,m),7.73-7.79(2H,m),8.15(1H,dd,J=7.8,1.7Hz),8.56-8.60(1H,m),9.23(1H,d,J=2.2Hz),10.96(1H,s).2-methoxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylpyridin-3-yl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.27 (3H, s), 3.28 (3H, s), 4.15 (3H, s), 7.19 (1H, t, J = 7.6 Hz), 7.32 (1H, d, J = 8.3Hz), 7.46-7.52 (1H, m), 7.53-7.60 (2H, m), 7.62-7.69 (1H, m), 7.73-7.79 (2H, m), 8.15 (1H, dd, J = 7.8,1.7Hz), 8.56-8.60 (1H, m), 9.23 (1H, d, J = 2.2Hz), 10.96 (1H, s).
実施例１９５
1H-NMR(DMSO-d6)δ値：2.76(6H,s),3.00(3H,s),3.19(2H,t,J=7.4Hz),4.14(2H,t,J=7.4Hz),7.13-7.20(1H,m),7.30(1H,d,J=7.6Hz),7.37-7.42(1H,m),7.44-7.53(4H,m),7.64-7.70(2H,m),7.89(1H,dd,J=7.8,1.7Hz),8.51(1H,d,J=1.7Hz),11.85(1H,s).Example 195
1 H-NMR (DMSO-d 6 ) δ value: 2.76 (6H, s), 3.00 (3H, s), 3.19 (2H, t, J = 7.4 Hz), 4.14 (2H, t, J = 7.4 Hz) 7.13-7.20 (1H, m), 7.30 (1H, d, J = 7.6Hz), 7.37-7.42 (1H, m), 7.44-7.53 (4H, m), 7.64-7.70 (2H, m), 7.89 (1H, dd, J = 7.8,1.7Hz), 8.51 (1H, d, J = 1.7Hz), 11.85 (1H, s).
実施例１９６
２−（ジメチルアミノ）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルピリジン−３−イル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.82(6H,s),3.26(3H,s),3.28(3H,s),7.31-7.38(1H,m),7.46-7.52(1H,m),7.53-7.66(4H,m),7.73-7.79(2H,m),8.16(1H,dd,J=7.8,1.5Hz),8.56(1H,d,J=2.2Hz),9.32(1H,d,J=2.2Hz),13.30(1H,s).Example 196
2- (Dimethylamino) -N- (2- (methyl (methylsulfonyl) amino) -5-phenylpyridin-3-yl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.82 (6H, s), 3.26 (3H, s), 3.28 (3H, s), 7.31-7.38 (1H, m), 7.46-7.52 (1H, m ), 7.53-7.66 (4H, m), 7.73-7.79 (2H, m), 8.16 (1H, dd, J = 7.8,1.5Hz), 8.56 (1H, d, J = 2.2Hz), 9.32 (1H, d, J = 2.2Hz), 13.30 (1H, s).
実施例１９７
1H-NMR(DMSO-d6)δ値：1.94-2.22(2H,m),2.83-2.91(2H,m),3.12(3H,s),3.72-3.78(2H,m),7.21(1H,s),7.23-7.56(8H,m),7.69(1H,s),7.75-7.81(2H,m),9.88(1H,s).Example 197
1 H-NMR (DMSO-d 6 ) δ value: 1.94-2.22 (2H, m), 2.83-2.91 (2H, m), 3.12 (3H, s), 3.72-3.78 (2H, m), 7.21 (1H , s), 7.23-7.56 (8H, m), 7.69 (1H, s), 7.75-7.81 (2H, m), 9.88 (1H, s).
実施例１９８
1H-NMR(DMSO-d6)δ値：3.21(3H,s),3.30(3H,s),7.33-7.53(4H,m),7.59(1H,ddd,J=7.9,7.9,1.7Hz),7.71(1H,ddd,J=7.6,4.9,1.2Hz),7.77(1H,d,J=8.5Hz),8.11(1H,ddd,J=7.7,7.7,1.7Hz),8.18-8.23(1H,m),8.72-8.78(2H,m),10.86(1H,s).Example 198
1 H-NMR (DMSO-d 6 ) δ value: 3.21 (3H, s), 3.30 (3H, s), 7.33-7.53 (4H, m), 7.59 (1H, ddd, J = 7.9, 7.9, 1.7 Hz ), 7.71 (1H, ddd, J = 7.6, 4.9, 1.2Hz), 7.77 (1H, d, J = 8.5Hz), 8.11 (1H, ddd, J = 7.7, 7.7, 1.7Hz), 8.18-8.23 ( 1H, m), 8.72-8.78 (2H, m), 10.86 (1H, s).
実施例１９９〜２０５
実施例１９８と同様にして、表２４に示す化合物を得た。Examples 199-205
In the same manner as in Example 198, compounds shown in Table 24 were obtained.
Ｎ−（５−（２−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.19(3H,s),3.31(3H,s),4.11(3H,s),7.16(1H,dd,J=7.6,7.6Hz),7.30(1H,d,J=8.3Hz),7.32-7.42(3H,m),7.44-7.52(1H,m),7.54-7.66(2H,m),7.76(1H,d,J=8.3Hz),8.12(1H,dd,J=7.8,1.2Hz),8.81(1H,s),10.84(1H,s).N- (5- (2-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -2-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.19 (3H, s), 3.31 (3H, s), 4.11 (3H, s), 7.16 (1H, dd, J = 7.6, 7.6 Hz), 7.30 ( 1H, d, J = 8.3Hz), 7.32-7.42 (3H, m), 7.44-7.52 (1H, m), 7.54-7.66 (2H, m), 7.76 (1H, d, J = 8.3Hz), 8.12 (1H, dd, J = 7.8,1.2Hz), 8.81 (1H, s), 10.84 (1H, s).
Ｎ−（５−（２−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−３−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.13(3H,s),3.27(3H,s),3.84(3H,s),7.16-7.24(1H,m),7.32-7.41(2H,m),7.44-7.52(5H,m),7.55-7.62(1H,m),7.75(1H,d,J=8.3Hz),8.30(1H,s),9.60(1H,s).N- (5- (2-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -3-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.13 (3H, s), 3.27 (3H, s), 3.84 (3H, s), 7.16-7.24 (1H, m), 7.32-7.41 (2H, m ), 7.44-7.52 (5H, m), 7.55-7.62 (1H, m), 7.75 (1H, d, J = 8.3Hz), 8.30 (1H, s), 9.60 (1H, s).
Ｎ−（５−（２−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−４−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.13(3H,s),3.27(3H,s),3.85(3H,s),7.11(2H,d,J=8.8Hz),7.31-7.40(2H,m),7.41-7.51(2H,m),7.54-7.62(1H,m),7.74(1H,d,J=8.3Hz),7.89(2H,d,J=8.8Hz),8.31(1H,s),9.45(1H,s).N- (5- (2-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -4-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.13 (3H, s), 3.27 (3H, s), 3.85 (3H, s), 7.11 (2H, d, J = 8.8 Hz), 7.31-7.40 ( 2H, m), 7.41-7.51 (2H, m), 7.54-7.62 (1H, m), 7.74 (1H, d, J = 8.3Hz), 7.89 (2H, d, J = 8.8Hz), 8.31 (1H , s), 9.45 (1H, s).
Ｎ−（５−（２−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２，４−ジメトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.19(3H,s),3.30(3H,s),3.87(3H,s),4.11(3H,s),6.74(1H,dd,J=8.8,2.2Hz),6.77(1H,d,J=2.2Hz),7.32-7.39(3H,m),7.44-7.51(1H,m),7.57(1H,ddd,J=7.9,7.9,1.5Hz),7.74(1H,d,J=8.3Hz),8.07(1H,d,J=8.8Hz),8.82(1H,s),10.71(1H,s).N- (5- (2-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -2,4-dimethoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.19 (3H, s), 3.30 (3H, s), 3.87 (3H, s), 4.11 (3H, s), 6.74 (1H, dd, J = 8.8 , 2.2Hz), 6.77 (1H, d, J = 2.2Hz), 7.32-7.39 (3H, m), 7.44-7.51 (1H, m), 7.57 (1H, ddd, J = 7.9, 7.9, 1.5Hz) , 7.74 (1H, d, J = 8.3Hz), 8.07 (1H, d, J = 8.8Hz), 8.82 (1H, s), 10.71 (1H, s).
Ｎ−（５−（２−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−４−メチルベンズアミド
1H-NMR(DMSO-d6)δ値：2.40(3H,s),3.12(3H,s),3.26(3H,s),7.32-7.41(4H,m),7.43-7.53(2H,m),7.58(1H,ddd,J=7.9,7.9,1.8Hz),7.74(1H,d,J=8.3Hz),7.79-7.85(2H,m),8.27-8.34(1H,m),9.52(1H,s).N- (5- (2-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -4-methylbenzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.40 (3H, s), 3.12 (3H, s), 3.26 (3H, s), 7.32-7.41 (4H, m), 7.43-7.53 (2H, m ), 7.58 (1H, ddd, J = 7.9, 7.9, 1.8Hz), 7.74 (1H, d, J = 8.3Hz), 7.79-7.85 (2H, m), 8.27-8.34 (1H, m), 9.52 ( 1H, s).
Ｎ−（５−（２−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンゾ［１，３］ジオキソール−５−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.26(3H,s),6.15(2H,s),7.10(1H,d,J=8.0Hz),7.31-7.39(2H,m),7.41-7.54(4H,m),7.57(1H,ddd,J=8.0,8.0,1.6Hz),7.73(1H,d,J=8.3Hz),8.23-8.27(1H,m),9.46(1H,s).N- (5- (2-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzo [1,3] dioxol-5-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.26 (3H, s), 6.15 (2H, s), 7.10 (1H, d, J = 8.0 Hz), 7.31-7.39 ( 2H, m), 7.41-7.54 (4H, m), 7.57 (1H, ddd, J = 8.0,8.0,1.6Hz), 7.73 (1H, d, J = 8.3Hz), 8.23-8.27 (1H, m) , 9.46 (1H, s).
Ｎ−（５−（２−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２，３−ジヒドロベンゾ［１，４］ジオキシン−６−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.26(3H,s),4.28-4.36(4H,m),7.03(1H,d,J=9.0Hz),7.31-7.39(2H,m),7.40-7.51(4H,m),7.54-7.60(1H,m),7.73(1H,d,J=8.3Hz),8.28(1H,s),9.42(1H,s).N- (5- (2-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -2,3-dihydrobenzo [1,4] dioxin-6-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.26 (3H, s), 4.28-4.36 (4H, m), 7.03 (1H, d, J = 9.0 Hz), 7.31 7.39 (2H, m), 7.40-7.51 (4H, m), 7.54-7.60 (1H, m), 7.73 (1H, d, J = 8.3Hz), 8.28 (1H, s), 9.42 (1H, s) .
実施例２０６
1H-NMR(DMSO-d6)δ値：2.79(6H,s),3.16(3H,s),3.30(3H,s),7.28(1H,dd,J=7.6,7.6Hz),7.32-7.40(3H,m),7.44-7.52(2H,m),7.54-7.61(2H,m),7.75(1H,d,J=8.3Hz),8.06(1H,dd,J=7.8,1.7Hz),8.87(1H,s),12.62(1H,s).Example 206
1 H-NMR (DMSO-d 6 ) δ value: 2.79 (6H, s), 3.16 (3H, s), 3.30 (3H, s), 7.28 (1H, dd, J = 7.6, 7.6 Hz), 7.32 7.40 (3H, m), 7.44-7.52 (2H, m), 7.54-7.61 (2H, m), 7.75 (1H, d, J = 8.3Hz), 8.06 (1H, dd, J = 7.8,1.7Hz) , 8.87 (1H, s), 12.62 (1H, s).
実施例２０７〜２１１
実施例２０６と同様にして、表２５に示す化合物を得た。Examples 207 to 211
In the same manner as in Example 206, the compounds shown in Table 25 were obtained.
Ｎ−（５−（２−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２，３−ジメトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.18(3H,s),3.30(3H,s),3.90(3H,s),3.97-4.00(3H,m),7.22-7.29(1H,m),7.31-7.42(4H,m),7.44-7.52(1H,m),7.54-7.67(2H,m),7.76(1H,d,J=8.0Hz),8.80(1H,s),10.91(1H,s).N- (5- (2-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -2,3-dimethoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.18 (3H, s), 3.30 (3H, s), 3.90 (3H, s), 3.97-4.00 (3H, m), 7.22-7.29 (1H, m ), 7.31-7.42 (4H, m), 7.44-7.52 (1H, m), 7.54-7.67 (2H, m), 7.76 (1H, d, J = 8.0Hz), 8.80 (1H, s), 10.91 ( 1H, s).
Ｎ−（５−（２−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンゾ［１，３］ジオキソール−４−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.20(3H,s),3.26(3H,s),6.18-6.30(2H,broad),7.04(1H,dd,J=7.9,7.9Hz),7.18-7.24(1H,m),7.32-7.43(3H,m),7.44-7.52(2H,m),7.55-7.61(1H,m),7.75(1H,d,J=8.3Hz),8.76(1H,s),10.10(1H,s).N- (5- (2-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzo [1,3] dioxole-4-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.20 (3H, s), 3.26 (3H, s), 6.18-6.30 (2H, broad), 7.04 (1H, dd, J = 7.9, 7.9 Hz), 7.18-7.24 (1H, m), 7.32-7.43 (3H, m), 7.44-7.52 (2H, m), 7.55-7.61 (1H, m), 7.75 (1H, d, J = 8.3Hz), 8.76 ( 1H, s), 10.10 (1H, s).
Ｎ−（５−（２−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２，３−ジヒドロベンゾ［１，４］ジオキシン−５−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.19(3H,s),3.29(3H,s),4.34-4.41(2H,m),4.55-4.62(2H,m),7.01(1H,dd,J=7.9,7.9Hz),7.14(1H,dd,J=7.8,1.7Hz),7.32-7.42(3H,m),7.44-7.52(1H,m),7.58(1H,ddd,J=8.0,8.0,1.6Hz),7.64(1H,dd,J=8.0,1.7Hz),7.75(1H,d,J=8.3Hz),8.79(1H,s),10.71(1H,s).N- (5- (2-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -2,3-dihydrobenzo [1,4] dioxin-5-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.19 (3H, s), 3.29 (3H, s), 4.34-4.41 (2H, m), 4.55-4.62 (2H, m), 7.01 (1H, dd , J = 7.9, 7.9Hz), 7.14 (1H, dd, J = 7.8,1.7Hz), 7.32-7.42 (3H, m), 7.44-7.52 (1H, m), 7.58 (1H, ddd, J = 8.0 , 8.0, 1.6Hz), 7.64 (1H, dd, J = 8.0, 1.7Hz), 7.75 (1H, d, J = 8.3Hz), 8.79 (1H, s), 10.71 (1H, s).
２−（ジフルオロメトキシ）−Ｎ−（５−（２−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.13(3H,s),3.25(3H,s),7.30(1H,t,J=73.0Hz),7.32-7.52(6H,m),7.54-7.61(1H,m),7.62-7.69(1H,m),7.76(1H,d,J=8.3Hz),7.90(1H,d,J=7.6Hz),8.48(1H,s),9.83(1H,s).2- (Difluoromethoxy) -N- (5- (2-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.13 (3H, s), 3.25 (3H, s), 7.30 (1H, t, J = 73.0 Hz), 7.32-7.52 (6H, m), 7.54- 7.61 (1H, m), 7.62-7.69 (1H, m), 7.76 (1H, d, J = 8.3Hz), 7.90 (1H, d, J = 7.6Hz), 8.48 (1H, s), 9.83 (1H , s).
２−（ジメチルアミノ）−Ｎ−（５−（２−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−３−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：2.91(6H,s),3.16(3H,s),3.30(3H,s),3.90(3H,s),7.27-7.32(1H,m),7.32-7.40(4H,m),7.44-7.51(1H,m),7.54-7.61(1H,m),7.76(1H,d,J=8.3Hz),7.84(1H,dd,J=7.9,1.3Hz),8.87(1H,s),13.64(1H,s).2- (Dimethylamino) -N- (5- (2-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -3-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.91 (6H, s), 3.16 (3H, s), 3.30 (3H, s), 3.90 (3H, s), 7.27-7.32 (1H, m), 7.32-7.40 (4H, m), 7.44-7.51 (1H, m), 7.54-7.61 (1H, m), 7.76 (1H, d, J = 8.3Hz), 7.84 (1H, dd, J = 7.9,1.3 Hz), 8.87 (1H, s), 13.64 (1H, s).
実施例２１２
1H-NMR(DMSO-d6)δ値：3.18(3H,s),3.29(3H,s),4.11(3H,s),7.13-7.20(1H,m),7.30(1H,d,J=8.3Hz),7.31-7.39(2H,m),7.48(1H,dd,J=8.3,2.2Hz),7.59-7.66(1H,m),7.70-7.78(3H,m),8.14(1H,dd,J=7.9,1.8Hz),8.87(1H,d,J=2.0Hz),10.84(1H,s).Example 212
1 H-NMR (DMSO-d 6 ) δ value: 3.18 (3H, s), 3.29 (3H, s), 4.11 (3H, s), 7.13-7.20 (1H, m), 7.30 (1H, d, J = 8.3Hz), 7.31-7.39 (2H, m), 7.48 (1H, dd, J = 8.3,2.2Hz), 7.59-7.66 (1H, m), 7.70-7.78 (3H, m), 8.14 (1H, dd, J = 7.9,1.8Hz), 8.87 (1H, d, J = 2.0Hz), 10.84 (1H, s).
実施例２１３〜２１６
実施例２１２と同様にして、表２６に示す化合物を得た。Examples 213-216
In the same manner as in Example 212, the compounds shown in Table 26 were obtained.
Ｎ−（５−（４−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−３−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.25(3H,s),3.84(3H,s),7.17-7.23(1H,m),7.31-7.38(2H,m),7.46-7.51(3H,m),7.56(1H,dd,J=8.3,2.2Hz),7.70-7.77(3H,m),8.37(1H,d,J=2.2Hz),9.58(1H,s).N- (5- (4-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -3-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.25 (3H, s), 3.84 (3H, s), 7.17-7.23 (1H, m), 7.31-7.38 (2H, m ), 7.46-7.51 (3H, m), 7.56 (1H, dd, J = 8.3,2.2Hz), 7.70-7.77 (3H, m), 8.37 (1H, d, J = 2.2Hz), 9.58 (1H, s).
Ｎ−（５−（４−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−４−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),3.85(3H,s),7.12(2H,d,J=8.8Hz),7.30-7.38(2H,m),7.53(1H,dd,J=8.3,2.0Hz),7.68-7.77(3H,m),7.90(2H,d,J=8.8Hz),8.38(1H,d,J=1.7Hz),9.44(1H,s).N- (5- (4-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -4-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 3.85 (3H, s), 7.12 (2H, d, J = 8.8 Hz), 7.30-7.38 ( 2H, m), 7.53 (1H, dd, J = 8.3,2.0Hz), 7.68-7.77 (3H, m), 7.90 (2H, d, J = 8.8Hz), 8.38 (1H, d, J = 1.7Hz) ), 9.44 (1H, s).
Ｎ−（５−（４−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンゾ［１，３］ジオキソール−５−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.25(3H,s),6.15(2H,s),7.10(1H,d,J=8.1Hz),7.30-7.38(2H,m),7.43(1H,d,J=1.7Hz),7.51(1H,dd,J=8.3,1.7Hz),7.54(1H,dd,J=8.4,2.3Hz),7.69-7.76(3H,m),8.32(1H,d,J=2.2Hz),9.45(1H,s).N- (5- (4-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzo [1,3] dioxol-5-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.25 (3H, s), 6.15 (2H, s), 7.10 (1H, d, J = 8.1 Hz), 7.30-7.38 ( 2H, m), 7.43 (1H, d, J = 1.7Hz), 7.51 (1H, dd, J = 8.3, 1.7Hz), 7.54 (1H, dd, J = 8.4, 2.3Hz), 7.69-7.76 (3H , m), 8.32 (1H, d, J = 2.2Hz), 9.45 (1H, s).
Ｎ−（５−（４−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２，３−ジヒドロベンゾ［１，４］ジオキシン−６−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.25(3H,s),4.28-4.36(4H,m),7.04(1H,d,J=9.0Hz),7.30-7.38(2H,m),7.40-7.46(2H,m),7.51-7.56(1H,m),7.68-7.77(3H,m),8.34(1H,d,J=1.2Hz),9.41(1H,s).N- (5- (4-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -2,3-dihydrobenzo [1,4] dioxin-6-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.25 (3H, s), 4.28-4.36 (4H, m), 7.04 (1H, d, J = 9.0 Hz), 7.30- 7.38 (2H, m), 7.40-7.46 (2H, m), 7.51-7.56 (1H, m), 7.68-7.77 (3H, m), 8.34 (1H, d, J = 1.2Hz), 9.41 (1H, s).
実施例２１７
1H-NMR(DMSO-d6)δ値：2.79(6H,s),3.14(3H,s),3.29(3H,s),7.25-7.39(3H,m),7.43-7.50(2H,m),7.54-7.61(1H,m),7.69-7.77(3H,m),8.06-8.13(1H,m),8.93(1H,d,J=2.0Hz),12.61(1H,s).Example 217
1 H-NMR (DMSO-d 6 ) δ value: 2.79 (6H, s), 3.14 (3H, s), 3.29 (3H, s), 7.25-7.39 (3H, m), 7.43-7.50 (2H, m ), 7.54-7.61 (1H, m), 7.69-7.77 (3H, m), 8.06-8.13 (1H, m), 8.93 (1H, d, J = 2.0Hz), 12.61 (1H, s).
実施例２１８〜２２２
実施例２１７と同様にして、表２７に示す化合物を得た。Examples 218-222
In the same manner as in Example 217, the compounds shown in Table 27 were obtained.
Ｎ−（５−（４−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２，３−ジメトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.17(3H,s),3.29(3H,s),3.90(3H,s),3.99(3H,s),7.26(1H,dd,J=7.8,7.8Hz),7.31-7.39(3H,m),7.49(1H,dd,J=8.3,1.7Hz),7.62-7.68(1H,m),7.70-7.77(3H,m),8.86(1H,d,J=1.7Hz),10.91(1H,s).N- (5- (4-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -2,3-dimethoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 3.29 (3H, s), 3.90 (3H, s), 3.99 (3H, s), 7.26 (1H, dd, J = 7.8 , 7.8Hz), 7.31-7.39 (3H, m), 7.49 (1H, dd, J = 8.3,1.7Hz), 7.62-7.68 (1H, m), 7.70-7.77 (3H, m), 8.86 (1H, d, J = 1.7Hz), 10.91 (1H, s).
Ｎ−（５−（４−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンゾ［１，３］ジオキソール−４−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.18(3H,s),3.25(3H,s),6.18-6.29(2H,broad),7.05(1H,dd,J=7.9,7.9Hz),7.21(1H,dd,J=7.7,1.1Hz),7.32-7.39(2H,m),7.45-7.51(2H,m),7.70-7.76(3H,m),8.81(1H,d,J=2.2Hz),10.09(1H,s).N- (5- (4-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzo [1,3] dioxole-4-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.18 (3H, s), 3.25 (3H, s), 6.18-6.29 (2H, broad), 7.05 (1H, dd, J = 7.9, 7.9 Hz), 7.21 (1H, dd, J = 7.7,1.1Hz), 7.32-7.39 (2H, m), 7.45-7.51 (2H, m), 7.70-7.76 (3H, m), 8.81 (1H, d, J = 2.2 Hz), 10.09 (1H, s).
Ｎ−（５−（４−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２，３−ジヒドロベンゾ［１，４］ジオキシン−５−カルボキサミド
1H-NMR(DMSO-d6)δ値：3.18(3H,s),3.27(3H,s),4.34-4.41(2H,m),4.54-4.62(2H,m),6.98-7.05(1H,m),7.11-7.16(1H,m),7.31-7.39(2H,m),7.45-7.50(1H,m),7.64-7.68(1H,m),7.69-7.76(3H,m),8.84(1H,d,J=2.0Hz),10.71(1H,s).N- (5- (4-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -2,3-dihydrobenzo [1,4] dioxin-5-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 3.18 (3H, s), 3.27 (3H, s), 4.34-4.41 (2H, m), 4.54-4.62 (2H, m), 6.98-7.05 (1H , m), 7.11-7.16 (1H, m), 7.31-7.39 (2H, m), 7.45-7.50 (1H, m), 7.64-7.68 (1H, m), 7.69-7.76 (3H, m), 8.84 (1H, d, J = 2.0Hz), 10.71 (1H, s).
２−（ジフルオロメトキシ）−Ｎ−（５−（４−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.24(3H,s),7.31(1H,t,J=73.0Hz),7.32-7.48(4H,m),7.54(1H,dd,J=8.3,2.2Hz),7.62-7.69(1H,m),7.69-7.77(3H,m),7.92(1H,d,J=7.8Hz),8.54(1H,s),9.82(1H,s).2- (Difluoromethoxy) -N- (5- (4-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.24 (3H, s), 7.31 (1H, t, J = 73.0 Hz), 7.32-7.48 (4H, m), 7.54 ( 1H, dd, J = 8.3,2.2Hz), 7.62-7.69 (1H, m), 7.69-7.77 (3H, m), 7.92 (1H, d, J = 7.8Hz), 8.54 (1H, s), 9.82 (1H, s).
２−（ジメチルアミノ）−Ｎ−（５−（４−フルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−３−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：2.90(6H,s),3.15(3H,s),3.29(3H,s),3.90(3H,s),7.27-7.39(4H,m),7.46(1H,dd,J=8.3,2.2Hz),7.69-7.76(3H,m),7.86(1H,dd,J=7.8,1.5Hz),8.93(1H,d,J=2.2Hz),13.63(1H,s).2- (Dimethylamino) -N- (5- (4-fluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -3-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.90 (6H, s), 3.15 (3H, s), 3.29 (3H, s), 3.90 (3H, s), 7.27-7.39 (4H, m), 7.46 (1H, dd, J = 8.3,2.2Hz), 7.69-7.76 (3H, m), 7.86 (1H, dd, J = 7.8,1.5Hz), 8.93 (1H, d, J = 2.2Hz), 13.63 (1H, s).
実施例２２３
1H-NMR(DMSO-d6)δ値：3.17(3H,s),3.28(3H,s),3.82(3H,s),4.11(3H,s),7.05-7.11(2H,m),7.16(1H,dd,J=7.4,7.4Hz),7.29(1H,d,J=8.0Hz),7.45(1H,dd,J=8.3,2.2Hz),7.59-7.66(3H,m),7.70(1H,d,J=8.3Hz),8.14(1H,dd,J=7.8,1.7Hz),8.85(1H,d,J=2.2Hz),10.81(1H,s).Example 223
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 3.28 (3H, s), 3.82 (3H, s), 4.11 (3H, s), 7.05-7.11 (2H, m), 7.16 (1H, dd, J = 7.4,7.4Hz), 7.29 (1H, d, J = 8.0Hz), 7.45 (1H, dd, J = 8.3,2.2Hz), 7.59-7.66 (3H, m), 7.70 (1H, d, J = 8.3Hz), 8.14 (1H, dd, J = 7.8,1.7Hz), 8.85 (1H, d, J = 2.2Hz), 10.81 (1H, s).
実施例２２４〜２２７
実施例２２３と同様にして、表２８に示す化合物を得た。Examples 224-227
In the same manner as in Example 223, the compounds shown in Table 28 were obtained.
３−メトキシ−Ｎ−（５−（４−メトキシフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.24(3H,s),3.82(3H,s),3.84(3H,s),7.04-7.11(2H,m),7.16-7.23(1H,m),7.44-7.56(4H,m),7.60-7.71(3H,m),8.34(1H,s),9.55(1H,s).3-methoxy-N- (5- (4-methoxyphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.24 (3H, s), 3.82 (3H, s), 3.84 (3H, s), 7.04-7.11 (2H, m), 7.16-7.23 (1H, m), 7.44-7.56 (4H, m), 7.60-7.71 (3H, m), 8.34 (1H, s), 9.55 (1H, s).
４−メトキシ−Ｎ−（５−（４−メトキシフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),3.81(3H,s),3.85(3H,s),7.04-7.09(2H,m),7.09-7.14(2H,m),7.50(1H,dd,J=8.3,2.2Hz),7.61-7.70(3H,m),7.87-7.93(2H,m),8.35(1H,d,J=2.2Hz),9.42(1H,s).4-Methoxy-N- (5- (4-methoxyphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 3.81 (3H, s), 3.85 (3H, s), 7.04-7.09 (2H, m), 7.09-7.14 (2H, m), 7.50 (1H, dd, J = 8.3,2.2Hz), 7.61-7.70 (3H, m), 7.87-7.93 (2H, m), 8.35 (1H, d, J = 2.2 Hz), 9.42 (1H, s).
２，４−ジメトキシ−Ｎ−（５−（４−メトキシフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.16(3H,s),3.27(3H,s),3.82(3H,s),3.87(3H,s),4.10(3H,s),6.71-6.79(2H,m),7.07(2H,d,J=8.6Hz),7.41(1H,dd,J=8.3,1.7Hz),7.62(2H,d,J=8.6Hz),7.67(1H,d,J=8.3Hz),8.09(1H,d,J=8.5Hz),8.86(1H,d,J=2.0Hz),10.68(1H,s).2,4-Dimethoxy-N- (5- (4-methoxyphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.16 (3H, s), 3.27 (3H, s), 3.82 (3H, s), 3.87 (3H, s), 4.10 (3H, s), 6.71 6.79 (2H, m), 7.07 (2H, d, J = 8.6Hz), 7.41 (1H, dd, J = 8.3,1.7Hz), 7.62 (2H, d, J = 8.6Hz), 7.67 (1H, d , J = 8.3Hz), 8.09 (1H, d, J = 8.5Hz), 8.86 (1H, d, J = 2.0Hz), 10.68 (1H, s).
Ｎ−（５−（４−メトキシフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−４−メチルベンズアミド
1H-NMR(DMSO-d6)δ値：2.40(3H,s),3.10(3H,s),3.25(3H,s),3.81(3H,s),7.07(2H,d,J=8.8Hz),7.38(2H,d,J=8.2Hz),7.51(1H,dd,J=8.3,2.2Hz),7.64(2H,d,J=8.8Hz),7.68(1H,d,J=8.3Hz),7.83(2H,d,J=8.2Hz),8.34(1H,d,J=2.2Hz),9.48(1H,s).N- (5- (4-methoxyphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -4-methylbenzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.40 (3H, s), 3.10 (3H, s), 3.25 (3H, s), 3.81 (3H, s), 7.07 (2H, d, J = 8.8 Hz), 7.38 (2H, d, J = 8.2Hz), 7.51 (1H, dd, J = 8.3, 2.2Hz), 7.64 (2H, d, J = 8.8Hz), 7.68 (1H, d, J = 8.3) Hz), 7.83 (2H, d, J = 8.2Hz), 8.34 (1H, d, J = 2.2Hz), 9.48 (1H, s).
実施例２２８
1H-NMR(DMSO-d6)δ値：2.37(3H,s),3.17(3H,s),3.29(3H,s),4.11(3H,s),7.13-7.20(1H,m),7.27-7.36(3H,m),7.47(1H,dd,J=8.3,2.1Hz),7.56-7.65(3H,m),7.71(1H,d,J=8.3Hz),8.14(1H,dd,J=7.9,1.8Hz),8.88(1H,d,J=2.1Hz),10.81(1H,s).Example 228
1 H-NMR (DMSO-d 6 ) δ value: 2.37 (3H, s), 3.17 (3H, s), 3.29 (3H, s), 4.11 (3H, s), 7.13-7.20 (1H, m), 7.27-7.36 (3H, m), 7.47 (1H, dd, J = 8.3,2.1Hz), 7.56-7.65 (3H, m), 7.71 (1H, d, J = 8.3Hz), 8.14 (1H, dd, J = 7.9,1.8Hz), 8.88 (1H, d, J = 2.1Hz), 10.81 (1H, s).
実施例２２９〜２３７
実施例２２８と同様にして、表２９に示す化合物を得た。Examples 229-237
In the same manner as in Example 228, the compounds shown in Table 29 were obtained.
３−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−メチルフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.37(3H,s),3.11(3H,s),3.25(3H,s),3.84(3H,s),7.16-7.23(1H,m),7.32(2H,d,J=8.0Hz),7.45-7.52(3H,m),7.55(1H,dd,J=8.3,2.2Hz),7.59(2H,d,J=8.0Hz),7.70(1H,d,J=8.3Hz),8.37(1H,d,J=2.2Hz),9.56(1H,s).3-Methoxy-N- (2- (methyl (methylsulfonyl) amino) -5- (4-methylphenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.37 (3H, s), 3.11 (3H, s), 3.25 (3H, s), 3.84 (3H, s), 7.16-7.23 (1H, m), 7.32 (2H, d, J = 8.0Hz), 7.45-7.52 (3H, m), 7.55 (1H, dd, J = 8.3,2.2Hz), 7.59 (2H, d, J = 8.0Hz), 7.70 (1H , d, J = 8.3Hz), 8.37 (1H, d, J = 2.2Hz), 9.56 (1H, s).
４−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−メチルフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.36(3H,s),3.11(3H,s),3.25(3H,s),3.85(3H,s),7.12(2H,d,J=8.8Hz),7.32(2H,d,J=8.1Hz),7.52(1H,dd,J=8.4,2.0Hz),7.59(2H,d,J=8.1Hz),7.69(1H,d,J=8.4Hz),7.90(2H,d,J=8.8Hz),8.37(1H,d,J=2.0Hz),9.42(1H,s).4-Methoxy-N- (2- (methyl (methylsulfonyl) amino) -5- (4-methylphenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.36 (3H, s), 3.11 (3H, s), 3.25 (3H, s), 3.85 (3H, s), 7.12 (2H, d, J = 8.8 Hz), 7.32 (2H, d, J = 8.1Hz), 7.52 (1H, dd, J = 8.4,2.0Hz), 7.59 (2H, d, J = 8.1Hz), 7.69 (1H, d, J = 8.4 Hz), 7.90 (2H, d, J = 8.8Hz), 8.37 (1H, d, J = 2.0Hz), 9.42 (1H, s).
２，４−ジメトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−メチルフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.37(3H,s),3.16(3H,s),3.28(3H,s),3.87(3H,s),4.10(3H,s),6.74(1H,dd,J=8.7,2.2Hz),6.77(1H,d,J=2.2Hz),7.32(2H,d,J=8.0Hz),7.44(1H,dd,J=8.3,2.1Hz),7.57(2H,d,J=8.0Hz),7.69(1H,d,J=8.3Hz),8.09(1H,d,J=8.7Hz),8.89(1H,d,J=2.1Hz),10.69(1H,s).2,4-Dimethoxy-N- (2- (methyl (methylsulfonyl) amino) -5- (4-methylphenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.37 (3H, s), 3.16 (3H, s), 3.28 (3H, s), 3.87 (3H, s), 4.10 (3H, s), 6.74 ( 1H, dd, J = 8.7,2.2Hz), 6.77 (1H, d, J = 2.2Hz), 7.32 (2H, d, J = 8.0Hz), 7.44 (1H, dd, J = 8.3,2.1Hz), 7.57 (2H, d, J = 8.0Hz), 7.69 (1H, d, J = 8.3Hz), 8.09 (1H, d, J = 8.7Hz), 8.89 (1H, d, J = 2.1Hz), 10.69 ( 1H, s).
４−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−メチルフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.36(3H,s),2.40(3H,s),3.10(3H,s),3.24(3H,s),7.32(2H,d,J=7.9Hz),7.38(2H,d,J=8.1Hz),7.54(1H,dd,J=8.3,2.3Hz),7.59(2H,d,J=7.9Hz),7.69(1H,d,J=8.3Hz),7.83(2H,d,J=8.1Hz),8.36(1H,d,J=2.3Hz),9.48(1H,s).4-Methyl-N- (2- (methyl (methylsulfonyl) amino) -5- (4-methylphenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.36 (3H, s), 2.40 (3H, s), 3.10 (3H, s), 3.24 (3H, s), 7.32 (2H, d, J = 7.9 Hz), 7.38 (2H, d, J = 8.1Hz), 7.54 (1H, dd, J = 8.3, 2.3Hz), 7.59 (2H, d, J = 7.9Hz), 7.69 (1H, d, J = 8.3 Hz), 7.83 (2H, d, J = 8.1Hz), 8.36 (1H, d, J = 2.3Hz), 9.48 (1H, s).
２−フルオロ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−メチルフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.37(3H,s),3.13(3H,s),3.24(3H,s),7.33(2H,d,J=7.9Hz),7.38-7.49(2H,m),7.54(1H,dd,J=8.3,2.2Hz),7.59(2H,d,J=7.9Hz),7.64-7.74(2H,m),7.98(1H,ddd,J=7.7,7.7,1.6Hz),8.53-8.59(1H,m),9.72(1H,d,J=10.0Hz).2-Fluoro-N- (2- (methyl (methylsulfonyl) amino) -5- (4-methylphenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.37 (3H, s), 3.13 (3H, s), 3.24 (3H, s), 7.33 (2H, d, J = 7.9 Hz), 7.38-7.49 ( 2H, m), 7.54 (1H, dd, J = 8.3,2.2Hz), 7.59 (2H, d, J = 7.9Hz), 7.64-7.74 (2H, m), 7.98 (1H, ddd, J = 7.7, 7.7, 1.6Hz), 8.53-8.59 (1H, m), 9.72 (1H, d, J = 10.0Hz).
３−フルオロ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−メチルフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.36(3H,s),3.09(3H,s),3.24(3H,s),7.32(2H,d,J=8.0Hz),7.46-7.53(1H,m),7.55-7.74(6H,m),7.75-7.79(1H,m),8.23(1H,d,J=2.2Hz),9.74(1H,s).3-Fluoro-N- (2- (methyl (methylsulfonyl) amino) -5- (4-methylphenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.36 (3H, s), 3.09 (3H, s), 3.24 (3H, s), 7.32 (2H, d, J = 8.0 Hz), 7.46-7.53 ( 1H, m), 7.55-7.74 (6H, m), 7.75-7.79 (1H, m), 8.23 (1H, d, J = 2.2Hz), 9.74 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−メチルフェニル）フェニル）ピリジン−２−カルボキサミド
1H-NMR(DMSO-d6)δ値：2.37(3H,s),3.19(3H,s),3.28(3H,s),7.33(2H,d,J=8.1Hz),7.51(1H,dd,J=8.4,2.1Hz),7.60(2H,d,J=8.1Hz),7.68-7.75(2H,m),8.12(1H,ddd,J=7.6,7.6,1.4Hz),8.22(1H,d,J=7.6Hz),8.73-8.78(1H,m),8.79(1H,d,J=2.1Hz),10.84(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (4-methylphenyl) phenyl) pyridine-2-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 2.37 (3H, s), 3.19 (3H, s), 3.28 (3H, s), 7.33 (2H, d, J = 8.1 Hz), 7.51 (1H, dd, J = 8.4, 2.1Hz), 7.60 (2H, d, J = 8.1Hz), 7.68-7.75 (2H, m), 8.12 (1H, ddd, J = 7.6, 7.6, 1.4Hz), 8.22 (1H , d, J = 7.6Hz), 8.73-8.78 (1H, m), 8.79 (1H, d, J = 2.1Hz), 10.84 (1H, s).
２，４−ジフルオロ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−メチルフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.37(3H,s),3.13(3H,s),3.24(3H,s),7.28-7.35(3H,m),7.50-7.61(4H,m),7.71(1H,d,J=8.3Hz),8.04(1H,ddd,J=8.8,8.8,6.7Hz),8.50-8.56(1H,m),9.69(1H,d,J=10.0Hz).2,4-Difluoro-N- (2- (methyl (methylsulfonyl) amino) -5- (4-methylphenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.37 (3H, s), 3.13 (3H, s), 3.24 (3H, s), 7.28-7.35 (3H, m), 7.50-7.61 (4H, m ), 7.71 (1H, d, J = 8.3Hz), 8.04 (1H, ddd, J = 8.8, 8.8, 6.7Hz), 8.50-8.56 (1H, m), 9.69 (1H, d, J = 10.0Hz) .
２，３−ジフルオロ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−メチルフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.37(3H,s),3.12(3H,s),3.23(3H,s),7.32(2H,d,J=8.0Hz),7.36-7.44(1H,m),7.54-7.62(3H,m),7.64-7.75(3H,m),8.42(1H,s),9.80(1H,d,J=6.1Hz).2,3-difluoro-N- (2- (methyl (methylsulfonyl) amino) -5- (4-methylphenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.37 (3H, s), 3.12 (3H, s), 3.23 (3H, s), 7.32 (2H, d, J = 8.0 Hz), 7.36-7.44 ( 1H, m), 7.54-7.62 (3H, m), 7.64-7.75 (3H, m), 8.42 (1H, s), 9.80 (1H, d, J = 6.1Hz).
実施例２３８
1H-NMR(DMSO-d6)δ値：2.37(3H,s),2.79(6H,s),3.14(3H,s),3.28(3H,s),7.25-7.35(3H,m),7.42-7.49(2H,m),7.54-7.61(3H,m),7.70(1H,d,J=8.3Hz),8.09(1H,dd,J=7.8,1.7Hz),8.93(1H,d,J=2.2Hz),12.57(1H,s).Example 238
1 H-NMR (DMSO-d 6 ) δ value: 2.37 (3H, s), 2.79 (6H, s), 3.14 (3H, s), 3.28 (3H, s), 7.25-7.35 (3H, m), 7.42-7.49 (2H, m), 7.54-7.61 (3H, m), 7.70 (1H, d, J = 8.3Hz), 8.09 (1H, dd, J = 7.8,1.7Hz), 8.93 (1H, d, J = 2.2Hz), 12.57 (1H, s).
実施例２３９〜２４１
実施例２３８と同様にして、表３０に示す化合物を得た。Examples 239-241
In the same manner as in Example 238, the compounds shown in Table 30 were obtained.
２，３−ジメトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−メチルフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.37(3H,s),3.16(3H,s),3.28(3H,s),3.90(3H,s),3.98(3H,s),7.26(1H,dd,J=7.9,7.9Hz),7.30-7.36(3H,m),7.48(1H,dd,J=8.2,2.1Hz),7.56-7.61(2H,m),7.62-7.67(1H,m),7.71(1H,d,J=8.3Hz),8.86(1H,d,J=2.0Hz),10.88(1H,s).2,3-Dimethoxy-N- (2- (methyl (methylsulfonyl) amino) -5- (4-methylphenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.37 (3H, s), 3.16 (3H, s), 3.28 (3H, s), 3.90 (3H, s), 3.98 (3H, s), 7.26 ( 1H, dd, J = 7.9,7.9Hz), 7.30-7.36 (3H, m), 7.48 (1H, dd, J = 8.2,2.1Hz), 7.56-7.61 (2H, m), 7.62-7.67 (1H, m), 7.71 (1H, d, J = 8.3Hz), 8.86 (1H, d, J = 2.0Hz), 10.88 (1H, s).
２−（ジメチルアミノ）−３−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−メチルフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.37(3H,s),2.90(6H,s),3.14(3H,s),3.28(3H,s),3.90(3H,s),7.27-7.39(4H,m),7.45(1H,dd,J=8.2,2.1Hz),7.55-7.61(2H,m),7.71(1H,d,J=8.3Hz),7.86(1H,d,J=7.8Hz),8.94(1H,d,J=2.1Hz),13.59(1H,s).2- (Dimethylamino) -3-methoxy-N- (2- (methyl (methylsulfonyl) amino) -5- (4-methylphenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.37 (3H, s), 2.90 (6H, s), 3.14 (3H, s), 3.28 (3H, s), 3.90 (3H, s), 7.27- 7.39 (4H, m), 7.45 (1H, dd, J = 8.2,2.1Hz), 7.55-7.61 (2H, m), 7.71 (1H, d, J = 8.3Hz), 7.86 (1H, d, J = 7.8Hz), 8.94 (1H, d, J = 2.1Hz), 13.59 (1H, s).
２−（ジフルオロメトキシ）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（４−メチルフェニル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.37(3H,s),3.11(3H,s),3.23(3H,s),7.10-7.49(5H,m),7.53(1H,dd,J=8.3,2.2Hz),7.55-7.61(2H,m),7.62-7.68(1H,m),7.71(1H,d,J=8.3Hz),7.91(1H,d,J=7.3Hz),8.54(1H,s),9.79(1H,s).2- (Difluoromethoxy) -N- (2- (methyl (methylsulfonyl) amino) -5- (4-methylphenyl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.37 (3H, s), 3.11 (3H, s), 3.23 (3H, s), 7.10-7.49 (5H, m), 7.53 (1H, dd, J = 8.3,2.2Hz), 7.55-7.61 (2H, m), 7.62-7.68 (1H, m), 7.71 (1H, d, J = 8.3Hz), 7.91 (1H, d, J = 7.3Hz), 8.54 (1H, s), 9.79 (1H, s).
実施例２４２
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.26(3H,s),3.85(3H,s),7.00-7.52(5H,m),7.58-8.00(4H,m),8.28(1H,s),9.45(1H,s).Example 242
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.26 (3H, s), 3.85 (3H, s), 7.00-7.52 (5H, m), 7.58-8.00 (4H, m ), 8.28 (1H, s), 9.45 (1H, s).
実施例２４３〜２４４
実施例２４２と同様にして、表３１に示す化合物を得た。Examples 243 to 244
In the same manner as in Example 242, compounds shown in Table 31 were obtained.
Ｎ−（５−（２，４−ジフルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.18(3H,s),3.30(3H,s),4.11(3H,s),7.16(1H,dd,J=7.5,7.5Hz),7.25(1H,ddd,J=8.5,8.5,2.4Hz),7.29(1H,d,J=8.5Hz),7.33-7.39(1H,m),7.42(1H,ddd,J=11.2,9.1,2.3Hz),7.58-7.67(2H,m),7.76(1H,d,J=8.3Hz),8.12(1H,dd,J=7.8,1.7Hz),8.78(1H,s),10.83(1H,s).N- (5- (2,4-difluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -2-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.18 (3H, s), 3.30 (3H, s), 4.11 (3H, s), 7.16 (1H, dd, J = 7.5, 7.5 Hz), 7.25 ( 1H, ddd, J = 8.5,8.5,2.4Hz), 7.29 (1H, d, J = 8.5Hz), 7.33-7.39 (1H, m), 7.42 (1H, ddd, J = 11.2,9.1,2.3Hz) 7.58-7.67 (2H, m), 7.76 (1H, d, J = 8.3Hz), 8.12 (1H, dd, J = 7.8, 1.7Hz), 8.78 (1H, s), 10.83 (1H, s).
Ｎ−（５−（２，４−ジフルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−３−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.26(3H,s),3.84(3H,s),7.16-7.30(2H,m),7.38-7.53(5H,m),7.59-7.69(1H,m),7.75(1H,d,J=8.0Hz),8.27(1H,s),9.60(1H,s).N- (5- (2,4-difluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -3-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.26 (3H, s), 3.84 (3H, s), 7.16-7.30 (2H, m), 7.38-7.53 (5H, m ), 7.59-7.69 (1H, m), 7.75 (1H, d, J = 8.0Hz), 8.27 (1H, s), 9.60 (1H, s).
実施例２４５
1H-NMR(DMSO-d6)δ値：3.17(3H,s),3.29(3H,s),3.90(3H,s),3.98(3H,s),7.22-7.29(2H,m),7.34(1H,dd,J=8.1,1.7Hz),7.37(1H,ddd,J=8.3,8.3,2.0Hz),7.42(1H,ddd,J=11.3,9.1,2.4Hz),7.59-7.68(2H,m),7.76(1H,d,J=8.3Hz),8.77(1H,s),10.91(1H,s).Example 245
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 3.29 (3H, s), 3.90 (3H, s), 3.98 (3H, s), 7.22-7.29 (2H, m), 7.34 (1H, dd, J = 8.1,1.7Hz), 7.37 (1H, ddd, J = 8.3,8.3,2.0Hz), 7.42 (1H, ddd, J = 11.3,9.1,2.4Hz), 7.59-7.68 ( 2H, m), 7.76 (1H, d, J = 8.3Hz), 8.77 (1H, s), 10.91 (1H, s).
実施例２４６
Ｎ−（５−（２，４−ジフルオロフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２−（ジメチルアミノ）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.79(6H,s),3.15(3H,s),3.29(3H,s),7.20-7.31(2H,m),7.31-7.37(1H,m),7.38-7.51(2H,m),7.54-7.68(2H,m),7.75(1H,d,J=8.3Hz),8.06(1H,dd,J=7.9,1.6Hz),8.84(1H,s),12.63(1H,s).Example 246
N- (5- (2,4-difluorophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -2- (dimethylamino) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.79 (6H, s), 3.15 (3H, s), 3.29 (3H, s), 7.20-7.31 (2H, m), 7.31-7.37 (1H, m ), 7.38-7.51 (2H, m), 7.54-7.68 (2H, m), 7.75 (1H, d, J = 8.3Hz), 8.06 (1H, dd, J = 7.9,1.6Hz), 8.84 (1H, s), 12.63 (1H, s).
実施例２４７
1H-NMR(DMSO-d6)δ値：2.38(3H,s),3.12(3H,s),3.26(3H,s),3.84(3H,s),7.13-7.24(3H,m),7.41-7.52(5H,m),7.73(1H,d,J=8.1Hz),8.28(1H,s),9.58(1H,s).Example 247
1 H-NMR (DMSO-d 6 ) δ value: 2.38 (3H, s), 3.12 (3H, s), 3.26 (3H, s), 3.84 (3H, s), 7.13-7.24 (3H, m), 7.41-7.52 (5H, m), 7.73 (1H, d, J = 8.1Hz), 8.28 (1H, s), 9.58 (1H, s).
実施例２４８〜２５０
実施例２４７と同様にして、表３２に示す化合物を得た。Examples 248-250
In the same manner as in Example 247, the compounds shown in Table 32 were obtained.
Ｎ−（５−（２−フルオロ−４−メチルフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−４−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：2.38(3H,s),3.12(3H,s),3.25(3H,s),3.85(3H,s),7.08-7.22(4H,m),7.38-7.50(2H,m),7.71(1H,d,J=8.3Hz),7.86-7.92(2H,m),8.26-8.30(1H,m),9.44(1H,s).N- (5- (2-Fluoro-4-methylphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -4-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.38 (3H, s), 3.12 (3H, s), 3.25 (3H, s), 3.85 (3H, s), 7.08-7.22 (4H, m), 7.38-7.50 (2H, m), 7.71 (1H, d, J = 8.3Hz), 7.86-7.92 (2H, m), 8.26-8.30 (1H, m), 9.44 (1H, s).
２，４−ジフルオロ−Ｎ−（５−（２−フルオロ−４−メチルフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.38(3H,s),3.14(3H,s),3.24(3H,s),7.14-7.23(2H,m),7.31(1H,ddd,J=8.5,8.5,2.4Hz),7.40-7.58(3H,m),7.74(1H,d,J=8.3Hz),7.97-8.07(1H,m),8.44(1H,s),9.71(1H,d,J=9.8Hz).2,4-Difluoro-N- (5- (2-fluoro-4-methylphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.38 (3H, s), 3.14 (3H, s), 3.24 (3H, s), 7.14-7.23 (2H, m), 7.31 (1H, ddd, J = 8.5, 8.5, 2.4Hz), 7.40-7.58 (3H, m), 7.74 (1H, d, J = 8.3Hz), 7.97-8.07 (1H, m), 8.44 (1H, s), 9.71 (1H, d, J = 9.8Hz).
２，３−ジフルオロ−Ｎ−（５−（２−フルオロ−４−メチルフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.38(3H,s),3.13(3H,s),3.24(3H,s),7.14-7.23(2H,m),7.36-7.50(3H,m),7.64-7.71(2H,m),7.73(1H,d,J=8.3Hz),8.34(1H,s),9.82(1H,d,J=6.1Hz).2,3-difluoro-N- (5- (2-fluoro-4-methylphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.38 (3H, s), 3.13 (3H, s), 3.24 (3H, s), 7.14-7.23 (2H, m), 7.36-7.50 (3H, m ), 7.64-7.71 (2H, m), 7.73 (1H, d, J = 8.3Hz), 8.34 (1H, s), 9.82 (1H, d, J = 6.1Hz).
実施例２５１
1H-NMR(DMSO-d6)δ値：2.38(3H,s),3.17(3H,s),3.29(3H,s),3.90(3H,s),3.98(3H,s),7.14-7.22(2H,m),7.25(1H,dd,J=8.1,8.1Hz),7.33(1H,dd,J=8.0,1.5Hz),7.37(1H,ddd,J=8.3,8.3,1.7Hz),7.45(1H,dd,J=8.1,8.1Hz),7.63(1H,dd,J=7.9,1.6Hz),7.73(1H,d,J=8.3Hz),8.78(1H,s),10.89(1H,s).Example 251
1 H-NMR (DMSO-d 6 ) δ value: 2.38 (3H, s), 3.17 (3H, s), 3.29 (3H, s), 3.90 (3H, s), 3.98 (3H, s), 7.14- 7.22 (2H, m), 7.25 (1H, dd, J = 8.1,8.1Hz), 7.33 (1H, dd, J = 8.0,1.5Hz), 7.37 (1H, ddd, J = 8.3,8.3,1.7Hz) , 7.45 (1H, dd, J = 8.1, 8.1Hz), 7.63 (1H, dd, J = 7.9, 1.6Hz), 7.73 (1H, d, J = 8.3Hz), 8.78 (1H, s), 10.89 ( 1H, s).
実施例２５２
1H-NMR(DMSO-d6)δ値：3.19(3H,s),3.31(3H,s),4.11(3H,s),7.17(1H,dd,J=7.4,7.4Hz),7.30(1H,d,J=8.6Hz),7.51-7.68(3H,m),7.80(1H,d,J=8.3Hz),8.05-8.20(2H,m),8.64(1H,d,J=4.6Hz),8.88-8.97(2H,m),10.86(1H,s).Example 252
1 H-NMR (DMSO-d 6 ) δ value: 3.19 (3H, s), 3.31 (3H, s), 4.11 (3H, s), 7.17 (1H, dd, J = 7.4, 7.4 Hz), 7.30 ( 1H, d, J = 8.6Hz), 7.51-7.68 (3H, m), 7.80 (1H, d, J = 8.3Hz), 8.05-8.20 (2H, m), 8.64 (1H, d, J = 4.6Hz ), 8.88-8.97 (2H, m), 10.86 (1H, s).
実施例２５３〜２５６
実施例２５２と同様にして、表３３に示す化合物を得た。Examples 253-256
In the same manner as in Example 252, compounds shown in Table 33 were obtained.
３−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（ピリジン−３−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.14(3H,s),3.28(3H,s),3.85(3H,s),7.17-7.25(1H,m),7.47-7.57(4H,m),7.66(1H,dd,J=8.4,2.1Hz),7.79(1H,d,J=8.3Hz),8.07-8.15(1H,m),8.44(1H,d,J=2.2Hz),8.63(1H,dd,J=4.7,1.6Hz),8.93(1H,d,J=1.7Hz),9.65(1H,s).3-Methoxy-N- (2- (methyl (methylsulfonyl) amino) -5- (pyridin-3-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.14 (3H, s), 3.28 (3H, s), 3.85 (3H, s), 7.17-7.25 (1H, m), 7.47-7.57 (4H, m ), 7.66 (1H, dd, J = 8.4, 2.1Hz), 7.79 (1H, d, J = 8.3Hz), 8.07-8.15 (1H, m), 8.44 (1H, d, J = 2.2Hz), 8.63 (1H, dd, J = 4.7,1.6Hz), 8.93 (1H, d, J = 1.7Hz), 9.65 (1H, s).
４−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（ピリジン−３−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.13(3H,s),3.27(3H,s),3.85(3H,s),7.08-7.16(2H,m),7.54(1H,dd,J=7.9,4.8Hz),7.63(1H,dd,J=8.3,2.2Hz),7.77(1H,d,J=8.3Hz),7.88-7.95(2H,m),8.07-8.14(1H,m),8.42(1H,d,J=2.2Hz),8.63(1H,dd,J=4.8,1.4Hz),8.88-8.95(1H,m),9.49(1H,s).4-Methoxy-N- (2- (methyl (methylsulfonyl) amino) -5- (pyridin-3-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.13 (3H, s), 3.27 (3H, s), 3.85 (3H, s), 7.08-7.16 (2H, m), 7.54 (1H, dd, J = 7.9,4.8Hz), 7.63 (1H, dd, J = 8.3,2.2Hz), 7.77 (1H, d, J = 8.3Hz), 7.88-7.95 (2H, m), 8.07-8.14 (1H, m) , 8.42 (1H, d, J = 2.2Hz), 8.63 (1H, dd, J = 4.8, 1.4Hz), 8.88-8.95 (1H, m), 9.49 (1H, s).
２，４−ジメトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（ピリジン−３−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.18(3H,s),3.30(3H,s),3.87(3H,s),4.11(3H,s),6.70-6.86(2H,m),7.48-7.63(2H,m),7.78(1H,d,J=8.3Hz),8.03-8.18(2H,m),8.58-8.68(1H,m),8.86-9.00(2H,m),10.74(1H,s).2,4-Dimethoxy-N- (2- (methyl (methylsulfonyl) amino) -5- (pyridin-3-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.18 (3H, s), 3.30 (3H, s), 3.87 (3H, s), 4.11 (3H, s), 6.70-6.86 (2H, m), 7.48-7.63 (2H, m), 7.78 (1H, d, J = 8.3Hz), 8.03-8.18 (2H, m), 8.58-8.68 (1H, m), 8.86-9.00 (2H, m), 10.74 ( 1H, s).
４−メチル−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（ピリジン−３−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.40(3H,s),3.12(3H,s),3.27(3H,s),7.36-7.42(2H,m),7.54(1H,dd,J=7.9,4.8Hz),7.64(1H,dd,J=8.3,2.2Hz),7.78(1H,d,J=8.3Hz),7.81-7.87(2H,m),8.06-8.15(1H,m),8.42(1H,d,J=2.0Hz),8.63(1H,dd,J=4.6,1.5Hz),8.92(1H,d,J=2.2Hz),9.56(1H,s).4-Methyl-N- (2- (methyl (methylsulfonyl) amino) -5- (pyridin-3-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.40 (3H, s), 3.12 (3H, s), 3.27 (3H, s), 7.36-7.42 (2H, m), 7.54 (1H, dd, J = 7.9,4.8Hz), 7.64 (1H, dd, J = 8.3,2.2Hz), 7.78 (1H, d, J = 8.3Hz), 7.81-7.87 (2H, m), 8.06-8.15 (1H, m) , 8.42 (1H, d, J = 2.0Hz), 8.63 (1H, dd, J = 4.6, 1.5Hz), 8.92 (1H, d, J = 2.2Hz), 9.56 (1H, s).
実施例２５７
得られたｔｅｒｔ−ブチル＝４−（３−（３−メトキシベンズアミド）−４−（メチル（メチルスルホニル）アミノ）フェニル）フェニル（メチル）カルバマートにトリフルオロ酢酸5.0mLを加え、室温で1時間攪拌した。減圧下で溶媒を留去し、飽和炭酸水素ナトリウム水溶液および酢酸エチルを加えた。有機層を分取し、飽和塩化ナトリウム水溶液で洗浄後、無水硫酸マグネシウムで乾燥させ、減圧下で溶媒を留去した。得られた残留物にジイソプロピルエーテルおよび酢酸エチルを加え、固形物をろ取し、白色固体の３−メトキシ−Ｎ−（５−（４−（メチルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド76mgを得た。
1H-NMR(DMSO-d6)δ値：2.72(3H,d,J=4.9Hz),3.09(3H,s),3.23(3H,s),3.84(3H,s),5.91(1H,q,J=4.9Hz),6.62-6.68(2H,m),7.16-7.23(1H,m),7.43-7.50(6H,m),7.61(1H,d,J=8.6Hz),8.28(1H,d,J=2.0Hz),9.50(1H,s).Example 257
To the resulting tert-butyl 4- (3- (3-methoxybenzamido) -4- (methyl (methylsulfonyl) amino) phenyl) phenyl (methyl) carbamate, 5.0 mL of trifluoroacetic acid was added and stirred at room temperature for 1 hour. did. The solvent was distilled off under reduced pressure, and a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate were added. The organic layer was separated, washed with a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Diisopropyl ether and ethyl acetate were added to the obtained residue, the solid was collected by filtration, and white solid 3-methoxy-N- (5- (4- (methylamino) phenyl) -2- (methyl (methylsulfonyl) was obtained. 76 mg)) amino) phenyl) benzamide was obtained.
1 H-NMR (DMSO-d 6 ) δ value: 2.72 (3H, d, J = 4.9 Hz), 3.09 (3H, s), 3.23 (3H, s), 3.84 (3H, s), 5.91 (1H, q, J = 4.9Hz), 6.62-6.68 (2H, m), 7.16-7.23 (1H, m), 7.43-7.50 (6H, m), 7.61 (1H, d, J = 8.6Hz), 8.28 (1H , d, J = 2.0 Hz), 9.50 (1H, s).
実施例２５８〜２５９
実施例２５７と同様にして、表３４に示す化合物を得た。Examples 258-259
In the same manner as in Example 257, the compounds shown in Table 34 were obtained.
４−メトキシ−Ｎ−（５−（４−（メチルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.72(3H,d,J=4.9Hz),3.09(3H,s),3.23(3H,s),3.85(3H,s),5.91(1H,q,J=4.9Hz),6.65(2H,d,J=8.5Hz),7.11(2H,d,J=8.5Hz),7.41-7.49(3H,m),7.60(1H,d,J=8.3Hz),7.89(2H,d,J=8.8Hz),8.29(1H,d,J=1.9Hz),9.36(1H,s).4-Methoxy-N- (5- (4- (methylamino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.72 (3H, d, J = 4.9 Hz), 3.09 (3H, s), 3.23 (3H, s), 3.85 (3H, s), 5.91 (1H, q, J = 4.9Hz), 6.65 (2H, d, J = 8.5Hz), 7.11 (2H, d, J = 8.5Hz), 7.41-7.49 (3H, m), 7.60 (1H, d, J = 8.3 Hz), 7.89 (2H, d, J = 8.8Hz), 8.29 (1H, d, J = 1.9Hz), 9.36 (1H, s).
Ｎ−（５−（４−（メチルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンゾ［１，３］ジオキソール−５−カルボキサミド
1H-NMR(DMSO-d6)δ値：2.72(3H,d,J=4.9Hz),3.08(3H,s),3.22(3H,s),5.91(1H,q,J=4.9Hz),6.13-6.17(2H,m),6.61-6.68(2H,m),7.10(1H,d,J=8.1Hz),7.40-7.52(5H,m),7.60(1H,d,J=8.3Hz),8.22(1H,d,J=1.4Hz),9.36(1H,s).N- (5- (4- (methylamino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzo [1,3] dioxole-5-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 2.72 (3H, d, J = 4.9 Hz), 3.08 (3H, s), 3.22 (3H, s), 5.91 (1H, q, J = 4.9 Hz) , 6.13-6.17 (2H, m), 6.61-6.68 (2H, m), 7.10 (1H, d, J = 8.1Hz), 7.40-7.52 (5H, m), 7.60 (1H, d, J = 8.3Hz ), 8.22 (1H, d, J = 1.4Hz), 9.36 (1H, s).
実施例２６０
得られたｔｅｒｔ−ブチル＝４−（３−（ベンゾ［１，３］ジオキソール−４−カルボキサミド）−４−（メチル（メチルスルホニル）アミノ）フェニル）フェニル（メチル）カルバマートにトリフルオロ酢酸5.0mLを加え、室温で1時間攪拌した。減圧下で溶媒を留去し、飽和炭酸水素ナトリウム水溶液および酢酸エチルを加えた。有機層を分取し、飽和塩化ナトリウム水溶液で洗浄後、無水硫酸マグネシウムで乾燥させ、減圧下で溶媒を留去した。得られた残留物にジイソプロピルエーテルを加え、固形物をろ取し、白色固体のＮ−（５−（４−（メチルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンゾ［１，３］ジオキソール−４−カルボキサミド54mgを得た。
1H-NMR(DMSO-d6)δ値：2.73(3H,d,J=4.8Hz),3.15(3H,s),3.23(3H,s),5.92(1H,q,J=4.8Hz),6.16-6.30(2H,broad),6.63-6.69(2H,m),7.05(1H,dd,J=7.9,7.9Hz),7.17-7.23(1H,m),7.38(1H,dd,J=8.3,2.2Hz),7.43-7.50(3H,m),7.60(1H,d,J=8.3Hz),8.74(1H,d,J=2.2Hz),10.03(1H,s).Example 260
To the obtained tert-butyl 4- (3- (benzo [1,3] dioxol-4-carboxamide) -4- (methyl (methylsulfonyl) amino) phenyl) phenyl (methyl) carbamate was added 5.0 mL of trifluoroacetic acid. The mixture was further stirred at room temperature for 1 hour. The solvent was distilled off under reduced pressure, and a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate were added. The organic layer was separated, washed with a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Diisopropyl ether was added to the obtained residue, and the solid substance was collected by filtration, and white solid N- (5- (4- (methylamino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzo [ 54 mg of 1,3] dioxole-4-carboxamide was obtained.
1 H-NMR (DMSO-d 6 ) δ value: 2.73 (3H, d, J = 4.8 Hz), 3.15 (3H, s), 3.23 (3H, s), 5.92 (1H, q, J = 4.8 Hz) , 6.16-6.30 (2H, broad), 6.63-6.69 (2H, m), 7.05 (1H, dd, J = 7.9,7.9Hz), 7.17-7.23 (1H, m), 7.38 (1H, dd, J = 8.3, 2.2Hz), 7.43-7.50 (3H, m), 7.60 (1H, d, J = 8.3Hz), 8.74 (1H, d, J = 2.2Hz), 10.03 (1H, s).
実施例２６１〜２６３
実施例２６０と同様にして、表３５に示す化合物を得た。Examples 261-263
In the same manner as in Example 260, the compounds shown in Table 35 were obtained.
Ｎ−（５−（４−（メチルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２，３−ジヒドロベンゾ［１，４］ジオキシン−５−カルボキサミド
1H-NMR(DMSO-d6)δ値：2.73(3H,d,J=5.0Hz),3.15(3H,s),3.25(3H,s),4.34-4.40(2H,m),4.54-4.61(2H,m),5.91(1H,q,J=5.0Hz),6.66(2H,d,J=8.6Hz),7.01(1H,dd,J=7.9,7.9Hz),7.10-7.16(1H,m),7.37(1H,dd,J=8.3,2.2Hz),7.45(2H,d,J=8.6Hz),7.61(1H,d,J=8.3Hz),7.64-7.69(1H,m),8.77(1H,d,J=2.0Hz),10.64(1H,s).N- (5- (4- (methylamino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -2,3-dihydrobenzo [1,4] dioxin-5-carboxamide
1 H-NMR (DMSO-d 6 ) δ value: 2.73 (3H, d, J = 5.0 Hz), 3.15 (3H, s), 3.25 (3H, s), 4.34-4.40 (2H, m), 4.54- 4.61 (2H, m), 5.91 (1H, q, J = 5.0Hz), 6.66 (2H, d, J = 8.6Hz), 7.01 (1H, dd, J = 7.9,7.9Hz), 7.10-7.16 (1H , m), 7.37 (1H, dd, J = 8.3, 2.2Hz), 7.45 (2H, d, J = 8.6Hz), 7.61 (1H, d, J = 8.3Hz), 7.64-7.69 (1H, m) , 8.77 (1H, d, J = 2.0Hz), 10.64 (1H, s).
２，３−ジメトキシ−Ｎ−（５−（４−（メチルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.73(3H,d,J=4.8Hz),3.14(3H,s),3.26(3H,s),3.90(3H,s),3.97(3H,s),5.91(1H,q,J=4.8Hz),6.66(2H,d,J=8.6Hz),7.25(1H,dd,J=7.9,7.9Hz),7.30-7.35(1H,m),7.38(1H,dd,J=8.3,2.0Hz),7.45(2H,d,J=8.6Hz),7.60-7.67(2H,m),8.77(1H,d,J=2.0Hz),10.81(1H,s).2,3-dimethoxy-N- (5- (4- (methylamino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.73 (3H, d, J = 4.8 Hz), 3.14 (3H, s), 3.26 (3H, s), 3.90 (3H, s), 3.97 (3H, s), 5.91 (1H, q, J = 4.8Hz), 6.66 (2H, d, J = 8.6Hz), 7.25 (1H, dd, J = 7.9, 7.9Hz), 7.30-7.35 (1H, m), 7.38 (1H, dd, J = 8.3,2.0Hz), 7.45 (2H, d, J = 8.6Hz), 7.60-7.67 (2H, m), 8.77 (1H, d, J = 2.0Hz), 10.81 (1H , s).
２−（ジフルオロメトキシ）−Ｎ−（５−（４−（メチルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.72(3H,d,J=5.1Hz),3.09(3H,s),3.21(3H,s),5,89-5.96(1H,m),6.62-6.69(2H,m),7.30(1H,t,J=73.1Hz),7.36-7.49(5H,m),7.59-7.68(2H,m),7.91(1H,d,J=7.8Hz),8.45(1H,s),9.71(1H,s).2- (Difluoromethoxy) -N- (5- (4- (methylamino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.72 (3H, d, J = 5.1 Hz), 3.09 (3H, s), 3.21 (3H, s), 5,89-5.96 (1H, m), 6.62-6.69 (2H, m), 7.30 (1H, t, J = 73.1Hz), 7.36-7.49 (5H, m), 7.59-7.68 (2H, m), 7.91 (1H, d, J = 7.8Hz) , 8.45 (1H, s), 9.71 (1H, s).
実施例２６４
得られた２−（３−（４−メトキシベンズアミド）−４−（メチル（メチルスルホニル）アミノ）フェニル）フェニル＝アセタートにジオキサン2.0mLおよび2mol/L水酸化ナトリウム水溶液0.23mLを加え、室温で1時間30分間攪拌した。反応混合物にジオキサン1.0mLおよび水0.5mLを加え、室温で8時間攪拌した。反応混合物に2mol/L水酸化ナトリウム水溶液0.15mLを加え、室温で1時間攪拌した。反応混合物に10％クエン酸水溶液10mLおよび酢酸エチル10mLを加えた。有機層を分取し、飽和塩化ナトリウム水溶液で洗浄後、無水硫酸マグネシウムで乾燥させ、減圧下で溶媒を留去した。得られた残留物をシリカゲルカラムクロマトグラフィー［溶離液；70-55％ヘキサン／酢酸エチル］で精製し、白色固体のＮ−（５−（２−ヒドロキシフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−４−メトキシベンズアミド58mgを得た。
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),3.85(3H,s),6.87-6.94(1H,m),6.97(1H,d,J=8.0Hz),7.07-7.14(2H,m),7.16-7.23(1H,m),7.29(1H,d,J=7.6Hz),7.43(1H,dd,J=8.3,2.0Hz),7.63(1H,d,J=8.5Hz),7.85-7.91(2H,m),8.27(1H,d,J=1.7Hz),9.38(1H,s),9.66(1H,s).Example 264
To the obtained 2- (3- (4-methoxybenzamido) -4- (methyl (methylsulfonyl) amino) phenyl) phenyl acetate, 2.0 mL of dioxane and 0.23 mL of 2 mol / L aqueous sodium hydroxide solution were added, and the mixture was stirred at room temperature. Stir for 30 minutes. To the reaction mixture were added 1.0 mL of dioxane and 0.5 mL of water, and the mixture was stirred at room temperature for 8 hours. To the reaction mixture was added 0.15 mL of a 2 mol / L aqueous sodium hydroxide solution, and the mixture was stirred at room temperature for 1 hour. 10 mL of 10% aqueous citric acid solution and 10 mL of ethyl acetate were added to the reaction mixture. The organic layer was separated, washed with a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 70-55% hexane / ethyl acetate], and white solid N- (5- (2-hydroxyphenyl) -2- (methyl (methylsulfonyl) 58 mg of amino) phenyl) -4-methoxybenzamide were obtained.
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 3.85 (3H, s), 6.87-6.94 (1H, m), 6.97 (1H, d, J = 8.0Hz), 7.07-7.14 (2H, m), 7.16-7.23 (1H, m), 7.29 (1H, d, J = 7.6Hz), 7.43 (1H, dd, J = 8.3,2.0Hz), 7.63 (1H, d, J = 8.5Hz), 7.85-7.91 (2H, m), 8.27 (1H, d, J = 1.7Hz), 9.38 (1H, s), 9.66 (1H, s).
実施例２６５〜２６６
実施例２６４と同様にして、表３６に示す化合物を得た。Examples 265-266
In the same manner as in Example 264, the compounds shown in Table 36 were obtained.
Ｎ−（５−（２−ヒドロキシフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.17(3H,s),3.29(3H,s),4.11(3H,s),6.88-6.94(1H,m),6.97(1H,d,J=8.0Hz),7.11-7.24(2H,m),7.26-7.32(2H,m),7.38(1H,dd,J=8.3,2.0Hz),7.57-7.68(2H,m),8.11(1H,dd,J=7.8,1.7Hz),8.77(1H,d,J=1.9Hz),9.65(1H,s),10.76(1H,s).N- (5- (2-hydroxyphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -2-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.17 (3H, s), 3.29 (3H, s), 4.11 (3H, s), 6.88-6.94 (1H, m), 6.97 (1H, d, J = 8.0Hz), 7.11-7.24 (2H, m), 7.26-7.32 (2H, m), 7.38 (1H, dd, J = 8.3,2.0Hz), 7.57-7.68 (2H, m), 8.11 (1H, dd, J = 7.8, 1.7 Hz), 8.77 (1 H, d, J = 1.9 Hz), 9.65 (1 H, s), 10.76 (1 H, s).
Ｎ−（５−（２−ヒドロキシフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−３−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),3.84(3H,s),6.91(1H,dd,J=7.4,7.4Hz),6.97(1H,d,J=8.0Hz),7.15-7.24(2H,m),7.30(1H,d,J=7.6Hz),7.42-7.50(4H,m),7.64(1H,d,J=8.3Hz),8.27(1H,d,J=1.7Hz),9.52(1H,s),9.68(1H,s).N- (5- (2-hydroxyphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -3-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 3.84 (3H, s), 6.91 (1H, dd, J = 7.4, 7.4 Hz), 6.97 ( 1H, d, J = 8.0Hz), 7.15-7.24 (2H, m), 7.30 (1H, d, J = 7.6Hz), 7.42-7.50 (4H, m), 7.64 (1H, d, J = 8.3Hz ), 8.27 (1H, d, J = 1.7Hz), 9.52 (1H, s), 9.68 (1H, s).
実施例２６７〜２６９
実施例９３と同様にして、表３７に示す化合物を得た。Examples 267-269
In the same manner as in Example 93, the compounds shown in Table 37 were obtained.
２，４−ジフルオロ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.14(3H,s),3.25(3H,s),7.32(1H,ddd,J=8.3,8.3,2.4Hz),7.40-7.47(1H,m),7.49-7.60(4H,m),7.66-7.72(2H,m),7.74(1H,d,J=8.3Hz),8.04(1H,ddd,J=8.8,8.8,6.6Hz),8.51-8.58(1H,m),9.71(1H,d,J=9.8Hz).2,4-Difluoro-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.14 (3H, s), 3.25 (3H, s), 7.32 (1H, ddd, J = 8.3, 8.3, 2.4 Hz), 7.40-7.47 (1H, m ), 7.49-7.60 (4H, m), 7.66-7.72 (2H, m), 7.74 (1H, d, J = 8.3Hz), 8.04 (1H, ddd, J = 8.8,8.8,6.6Hz), 8.51- 8.58 (1H, m), 9.71 (1H, d, J = 9.8Hz).
２，３−ジフルオロ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.13(3H,s),3.24(3H,s),7.37-7.46(2H,m),7.49-7.55(2H,m),7.59(1H,dd,J=8.3,2.2Hz),7.65-7.76(5H,m),8.44(1H,s),9.82(1H,d,J=6.1Hz).2,3-difluoro-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.13 (3H, s), 3.24 (3H, s), 7.37-7.46 (2H, m), 7.49-7.55 (2H, m), 7.59 (1H, dd , J = 8.3, 2.2 Hz), 7.65-7.76 (5 H, m), 8.44 (1 H, s), 9.82 (1 H, d, J = 6.1 Hz).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）−２−ナフタミド
1H-NMR(DMSO-d6)δ値：3.14(3H,s),3.29(3H,s),7.40-7.46(1H,m),7.49-7.56(2H,m),7.57-7.77(6H,m),7.97-8.13(4H,m),8.38(1H,d,J=2.2Hz),8.57(1H,s),9.81(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) -2-naphthamide
1 H-NMR (DMSO-d 6 ) δ value: 3.14 (3H, s), 3.29 (3H, s), 7.40-7.46 (1H, m), 7.49-7.56 (2H, m), 7.57-7.77 (6H , m), 7.97-8.13 (4H, m), 8.38 (1H, d, J = 2.2Hz), 8.57 (1H, s), 9.81 (1H, s).
実施例２７０〜２７３
実施例１２５と同様にして、表３８に示す化合物を得た。Examples 270-273
In the same manner as in Example 125, the compounds shown in Table 38 were obtained.
３−（ジフルオロメトキシ）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.25(3H,s),7.34(1H,t,J=73.7Hz),7.39-7.55(4H,m),7.57-7.75(6H,m),7.77-7.82(1H,m),8.24-8.29(1H,m),9.75(1H,s).3- (Difluoromethoxy) -N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.25 (3H, s), 7.34 (1H, t, J = 73.7 Hz), 7.39-7.55 (4H, m), 7.57- 7.75 (6H, m), 7.77-7.82 (1H, m), 8.24-8.29 (1H, m), 9.75 (1H, s).
４−（ジフルオロメトキシ）−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.10(3H,s),3.25(3H,s),7.18-7.62(7H,m),7.64-7.76(3H,m),7.94-8.06(2H,m),8.26-8.34(1H,m),9.65(1H,s).4- (Difluoromethoxy) -N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.10 (3H, s), 3.25 (3H, s), 7.18-7.62 (7H, m), 7.64-7.76 (3H, m), 7.94-8.06 (2H) , m), 8.26-8.34 (1H, m), 9.65 (1H, s).
２−（ジメチルアミノ）−３−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.90(6H,s),3.15(3H,s),3.29(3H,s),3.90(3H,s),7.30(1H,dd,J=8.3,1.5Hz),7.36(1H,dd,J=7.9,7.9Hz),7.39-7.45(1H,m),7.47(1H,dd,J=8.3,2.2Hz),7.49-7.55(2H,m),7.65-7.71(2H,m),7.73(1H,d,J=8.3Hz),7.85(1H,dd,J=7.9,1.6Hz),8.95(1H,d,J=2.2Hz),13.60(1H,s).2- (Dimethylamino) -3-methoxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.90 (6H, s), 3.15 (3H, s), 3.29 (3H, s), 3.90 (3H, s), 7.30 (1H, dd, J = 8.3 1.5Hz), 7.36 (1H, dd, J = 7.9,7.9Hz), 7.39-7.45 (1H, m), 7.47 (1H, dd, J = 8.3,2.2Hz), 7.49-7.55 (2H, m) , 7.65-7.71 (2H, m), 7.73 (1H, d, J = 8.3Hz), 7.85 (1H, dd, J = 7.9,1.6Hz), 8.95 (1H, d, J = 2.2Hz), 13.60 ( 1H, s).
２−（ジメチルアミノ）−４−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−フェニルフェニル）ベンズアミド
1H-NMR(CDCl3)δ値：2.85(6H,s),3.02(3H,s),3.29(3H,s),3.87(3H,s),6.77(1H,dd,J=8.8,2.4Hz),6.84(1H,d,J=2.4Hz),7.32-7.49(5H,m),7.62-7.70(2H,m),8.24(1H,d,J=8.8Hz),8.99(1H,s),12.38(1H,s).2- (Dimethylamino) -4-methoxy-N- (2- (methyl (methylsulfonyl) amino) -5-phenylphenyl) benzamide
1 H-NMR (CDCl 3 ) δ value: 2.85 (6H, s), 3.02 (3H, s), 3.29 (3H, s), 3.87 (3H, s), 6.77 (1H, dd, J = 8.8, 2.4 Hz), 6.84 (1H, d, J = 2.4Hz), 7.32-7.49 (5H, m), 7.62-7.70 (2H, m), 8.24 (1H, d, J = 8.8Hz), 8.99 (1H, s ), 12.38 (1H, s).
実施例２７４〜２７５
実施例４５と同様にして、表３９に示す化合物を得た。Examples 274-275
In the same manner as in Example 45, the compounds shown in Table 39 were obtained.
Ｎ−（５−（２−フルオロ−４−メチルフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：2.38(3H,s),3.12(3H,s),3.26(3H,s),7.13-7.22(2H,m),7.41-7.50(2H,m),7.54-7.66(3H,m),7.73(1H,d,J=8.5Hz),7.89-7.95(2H,m),8.26(1H,s),9.60(1H,s).N- (5- (2-fluoro-4-methylphenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.38 (3H, s), 3.12 (3H, s), 3.26 (3H, s), 7.13-7.22 (2H, m), 7.41-7.50 (2H, m ), 7.54-7.66 (3H, m), 7.73 (1H, d, J = 8.5Hz), 7.89-7.95 (2H, m), 8.26 (1H, s), 9.60 (1H, s).
Ｎ−（５−（６−メトキシピリジン−３−イル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),3.92(3H,s),6.96(1H,d,J=8.6Hz),7.55-7.67(4H,m),7.73(1H,d,J=8.3Hz),7.90-7.97(2H,m),8.01-8.06(1H,m),8.32(1H,d,J=2.0Hz),8.51(1H,d,J=2.4Hz),9.62(1H,s).N- (5- (6-methoxypyridin-3-yl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 3.92 (3H, s), 6.96 (1H, d, J = 8.6 Hz), 7.55-7.67 ( 4H, m), 7.73 (1H, d, J = 8.3Hz), 7.90-7.97 (2H, m), 8.01-8.06 (1H, m), 8.32 (1H, d, J = 2.0Hz), 8.51 (1H , d, J = 2.4Hz), 9.62 (1H, s).
実施例２７６
1H-NMR(DMSO-d6)δ値：2.38(3H,s),3.18(3H,s),3.30(3H,s),4.11(3H,s),7.13-7.22(3H,m),7.29(1H,d,J=8.3Hz),7.33-7.39(1H,m),7.45(1H,dd,J=8.2,8.2Hz),7.58-7.65(1H,m),7.74(1H,d,J=8.0Hz),8.12(1H,dd,J=7.8,1.9Hz),8.79(1H,s),10.82(1H,s).Example 276
1 H-NMR (DMSO-d 6 ) δ value: 2.38 (3H, s), 3.18 (3H, s), 3.30 (3H, s), 4.11 (3H, s), 7.13-7.22 (3H, m), 7.29 (1H, d, J = 8.3Hz), 7.33-7.39 (1H, m), 7.45 (1H, dd, J = 8.2,8.2Hz), 7.58-7.65 (1H, m), 7.74 (1H, d, J = 8.0Hz), 8.12 (1H, dd, J = 7.8,1.9Hz), 8.79 (1H, s), 10.82 (1H, s).
実施例２７７
Ｎ−（５−（４−（ジメチルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：2.96(6H,s),3.15(3H,s),3.27(3H,s),4.10(3H,s),6.84(2H,d,J=8.8Hz),7.16(1H,dd,J=7.6,7.6Hz),7.29(1H,d,J=8.5Hz),7.41(1H,dd,J=8.2,2.1Hz),7.54(2H,d,J=8.8Hz),7.58-7.69(2H,m),8.15(1H,dd,J=7.9,1.8Hz),8.83(1H,d,J=2.2Hz),10.78(1H,s).Example 277
N- (5- (4- (dimethylamino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -2-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 2.96 (6H, s), 3.15 (3H, s), 3.27 (3H, s), 4.10 (3H, s), 6.84 (2H, d, J = 8.8 Hz), 7.16 (1H, dd, J = 7.6,7.6Hz), 7.29 (1H, d, J = 8.5Hz), 7.41 (1H, dd, J = 8.2,2.1Hz), 7.54 (2H, d, J = 8.8Hz), 7.58-7.69 (2H, m), 8.15 (1H, dd, J = 7.9,1.8Hz), 8.83 (1H, d, J = 2.2Hz), 10.78 (1H, s).
実施例２７８
得られたｔｅｒｔ−ブチル＝４−（３−（２−メトキシベンズアミド）−４−（メチル（メチルスルホニル）アミノ）フェニル）フェニル（メチル）カルバマートに塩化メチレン1.5mLおよびトリフルオロ酢酸0.5mLを加え、室温で1時間30分間攪拌した。減圧下で溶媒を留去し、飽和炭酸水素ナトリウム水溶液および酢酸エチルを加えた。有機層を分取し、飽和炭酸水素ナトリウム水溶液および飽和塩化ナトリウム水溶液で順次洗浄後、無水硫酸マグネシウムで乾燥させ、減圧下で溶媒を留去した。得られた残留物にジイソプロピルエーテルを加え、固形物をろ取し、白色固体の２−メトキシ−Ｎ−（５−（４−（メチルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド92mgを得た。
1H-NMR(DMSO-d6)δ値：2.73(3H,d,J=5.0Hz),3.15(3H,s),3.27(3H,s),4.10(3H,s),5.91(1H,q,J=5.0Hz),6.63-6.68(2H,m),7.13-7.19(1H,m),7.29(1H,d,J=7.8Hz),7.38(1H,dd,J=8.4,2.3Hz),7.43-7.48(2H,m),7.58-7.65(2H,m),8.14(1H,dd,J=7.8,1.9Hz),8.79(1H,d,J=2.3Hz),10.76(1H,s).Example 278
To the resulting tert-butyl = 4- (3- (2-methoxybenzamido) -4- (methyl (methylsulfonyl) amino) phenyl) phenyl (methyl) carbamate was added 1.5 mL of methylene chloride and 0.5 mL of trifluoroacetic acid, Stir at room temperature for 1 hour 30 minutes. The solvent was distilled off under reduced pressure, and a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate were added. The organic layer was separated, washed successively with a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Diisopropyl ether was added to the obtained residue, and the solid was collected by filtration to give 2-methoxy-N- (5- (4- (methylamino) phenyl) -2- (methyl (methylsulfonyl) amino) as a white solid. 92 mg of phenyl) benzamide were obtained.
1 H-NMR (DMSO-d 6 ) δ value: 2.73 (3H, d, J = 5.0 Hz), 3.15 (3H, s), 3.27 (3H, s), 4.10 (3H, s), 5.91 (1H, q, J = 5.0Hz), 6.63-6.68 (2H, m), 7.13-7.19 (1H, m), 7.29 (1H, d, J = 7.8Hz), 7.38 (1H, dd, J = 8.4,2.3Hz ), 7.43-7.48 (2H, m), 7.58-7.65 (2H, m), 8.14 (1H, dd, J = 7.8,1.9Hz), 8.79 (1H, d, J = 2.3Hz), 10.76 (1H, s).
実施例２７９
Ｎ−（５−（インドリン−５−イル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２−メトキシベンズアミド
1H-NMR(DMSO-d6)δ値：3.00(2H,t,J=8.5Hz),3.15(3H,s),3.27(3H,s),3.49(2H,td,J=8.5,1.7Hz),4.10(3H,s),5.74(1H,s),6.59(1H,d,J=8.0Hz),7.13-7.19(1H,m),7.24-7.31(2H,m),7.34-7.39(2H,m),7.58-7.65(2H,m),8.14(1H,dd,J=7.8,1.7Hz),8.78(1H,d,J=2.2Hz),10.76(1H,s).Example 279
N- (5- (Indoline-5-yl) -2- (methyl (methylsulfonyl) amino) phenyl) -2-methoxybenzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.00 (2H, t, J = 8.5 Hz), 3.15 (3H, s), 3.27 (3H, s), 3.49 (2H, td, J = 8.5, 1.7 Hz), 4.10 (3H, s), 5.74 (1H, s), 6.59 (1H, d, J = 8.0Hz), 7.13-7.19 (1H, m), 7.24-7.31 (2H, m), 7.34-7.39 (2H, m), 7.58-7.65 (2H, m), 8.14 (1H, dd, J = 7.8,1.7Hz), 8.78 (1H, d, J = 2.2Hz), 10.76 (1H, s).
実施例２８０
Ｎ−（５−（４−（エチルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：1.19(3H,t,J=7.1Hz),3.04-3.13(2H,m),3.09(3H,s),3.23(3H,s),5.82(1H,t,J=5.4Hz),6.64-6.69(2H,m),7.42-7.48(3H,m),7.54-7.66(4H,m),7.90-7.95(2H,m),8.26(1H,d,J=2.2Hz),9.52(1H,s).Example 280
N- (5- (4- (ethylamino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 1.19 (3H, t, J = 7.1 Hz), 3.04-3.13 (2H, m), 3.09 (3H, s), 3.23 (3H, s), 5.82 ( 1H, t, J = 5.4Hz), 6.64-6.69 (2H, m), 7.42-7.48 (3H, m), 7.54-7.66 (4H, m), 7.90-7.95 (2H, m), 8.26 (1H, d, J = 2.2Hz), 9.52 (1H, s).
実施例２８１
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.25(3H,s),7.31(2H,d,J=8.6Hz),7.32(1H,t,J=74.1Hz),7.54-7.67(4H,m),7.73(1H,d,J=8.6Hz),7.76(2H,d,J=8.6Hz),7.89-7.98(2H,m),8.34-8.39(1H,m),9.61(1H,s).Example 281
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.25 (3H, s), 7.31 (2H, d, J = 8.6 Hz), 7.32 (1H, t, J = 74.1 Hz) 7.54-7.67 (4H, m), 7.73 (1H, d, J = 8.6Hz), 7.76 (2H, d, J = 8.6Hz), 7.89-7.98 (2H, m), 8.34-8.39 (1H, m ), 9.61 (1H, s).
実施例２８２〜２８６
実施例２８１と同様にして、表４０に示す化合物を得た。Examples 282 to 286
In the same manner as in Example 281, compounds shown in Table 40 were obtained.
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（ピリジン−２−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.26(3H,s),7.41(1H,ddd,J=7.3,4.9,1.0Hz),7.55-7.67(3H,m),7.75(1H,d,J=8.3Hz),7.90-8.03(5H,m),8.69-8.74(1H,m),8.79(1H,d,J=2.2Hz),9.64(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (pyridin-2-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.26 (3H, s), 7.41 (1H, ddd, J = 7.3, 4.9, 1.0 Hz), 7.55-7.67 (3H, m ), 7.75 (1H, d, J = 8.3Hz), 7.90-8.03 (5H, m), 8.69-8.74 (1H, m), 8.79 (1H, d, J = 2.2Hz), 9.64 (1H, s) .
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（ピリミジン−２−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.27(3H,s),7.51(1H,dd,J=4.9,4.9Hz),7.54-7.68(3H,m),7.79(1H,d,J=8.5Hz),7.92-7.97(2H,m),8.29(1H,dd,J=8.5,2.0Hz),8.94-8.99(2H,m),9.12(1H,d,J=2.0Hz),9.66(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (pyrimidin-2-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.27 (3H, s), 7.51 (1H, dd, J = 4.9, 4.9 Hz), 7.54-7.68 (3H, m), 7.79 (1H, d, J = 8.5Hz), 7.92-7.97 (2H, m), 8.29 (1H, dd, J = 8.5,2.0Hz), 8.94-8.99 (2H, m), 9.12 (1H, d, J = 2.0Hz), 9.66 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（ピリミジン−５−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.11(3H,s),3.26(3H,s),7.55-7.67(3H,m),7.74(1H,dd,J=8.3,2.2Hz),7.82(1H,d,J=8.3Hz),7.91-7.97(2H,m),8.41(1H,d,J=2.2Hz),9.17(2H,s),9.24(1H,s),9.71(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (pyrimidin-5-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.11 (3H, s), 3.26 (3H, s), 7.55-7.67 (3H, m), 7.74 (1H, dd, J = 8.3, 2.2 Hz), 7.82 (1H, d, J = 8.3Hz), 7.91-7.97 (2H, m), 8.41 (1H, d, J = 2.2Hz), 9.17 (2H, s), 9.24 (1H, s), 9.71 (1H , s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（１，２，３，４−テトラヒドロキノリン−６−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：1.78-1.87(2H,m),2.74(2H,t,J=6.2Hz),3.08(3H,s),3.19-3.25(5H,m),5.94(1H,s),6.53(1H,d,J=8.3Hz),7.18-7.25(2H,m),7.42(1H,dd,J=8.3,2.2Hz),7.54-7.66(4H,m),7.89-7.96(2H,m),8.23(1H,d,J=2.0Hz),9.49(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (1,2,3,4-tetrahydroquinolin-6-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 1.78-1.87 (2H, m), 2.74 (2H, t, J = 6.2 Hz), 3.08 (3H, s), 3.19-3.25 (5H, m), 5.94 (1H, s), 6.53 (1H, d, J = 8.3Hz), 7.18-7.25 (2H, m), 7.42 (1H, dd, J = 8.3,2.2Hz), 7.54-7.66 (4H, m) 7.89-7.96 (2H, m), 8.23 (1H, d, J = 2.0Hz), 9.49 (1H, s).
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（１Ｈ−ピロロ［２，３−ｂ］ピリジン−５−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.27(3H,s),6.53-6.58(1H,m),7.53-7.68(5H,m),7.74(1H,d,J=8.3Hz),7.92-7.97(2H,m),8.25(1H,d,J=2.0Hz),8.42(1H,d,J=1.7Hz),8.55(1H,d,J=2.0Hz),9.61(1H,s),11.79(1H,s).N- (2- (methyl (methylsulfonyl) amino) -5- (1H-pyrrolo [2,3-b] pyridin-5-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.27 (3H, s), 6.53-6.58 (1H, m), 7.53-7.68 (5H, m), 7.74 (1H, d , J = 8.3Hz), 7.92-7.97 (2H, m), 8.25 (1H, d, J = 2.0Hz), 8.42 (1H, d, J = 1.7Hz), 8.55 (1H, d, J = 2.0Hz ), 9.61 (1H, s), 11.79 (1H, s).
実施例２８７
1H-NMR(DMSO-d6)δ値：2.36(3H,s),3.11(3H,s),3.26(3H,s),7.55-7.67(3H,m),7.70-7.78(2H,m),7.87-7.98(4H,m),8.53-8.57(1H,m),8.75(1H,d,J=2.2Hz),9.62(1H,s).Example 287
1 H-NMR (DMSO-d 6 ) δ value: 2.36 (3H, s), 3.11 (3H, s), 3.26 (3H, s), 7.55-7.67 (3H, m), 7.70-7.78 (2H, m ), 7.87-7.98 (4H, m), 8.53-8.57 (1H, m), 8.75 (1H, d, J = 2.2Hz), 9.62 (1H, s).
実施例２８８
Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（ピラジン−２−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.12(3H,s),3.27(3H,s),7.55-7.67(3H,m),7.81(1H,d,J=8.3Hz),7.92-7.97(2H,m),8.06(1H,dd,J=8.3,2.2Hz),8.68(1H,d,J=2.4Hz),8.76-8.80(1H,m),8.83(1H,d,J=2.0Hz),9.30(1H,d,J=1.5Hz),9.69(1H,s).Example 288
N- (2- (methyl (methylsulfonyl) amino) -5- (pyrazin-2-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.12 (3H, s), 3.27 (3H, s), 7.55-7.67 (3H, m), 7.81 (1H, d, J = 8.3 Hz), 7.92 7.97 (2H, m), 8.06 (1H, dd, J = 8.3,2.2Hz), 8.68 (1H, d, J = 2.4Hz), 8.76-8.80 (1H, m), 8.83 (1H, d, J = 2.0Hz), 9.30 (1H, d, J = 1.5Hz), 9.69 (1H, s).
実施例２８９
得られたＮ−（５−（４−（イソプロピルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミドに酢酸エチル1mLおよび4moL/L塩化水素−ジオキサン溶液0.037mLを加え、減圧下で溶媒を留去した。得られた残留物にジイソプロピルエーテルおよび酢酸エチルを加え、固形物をろ取し、白色固体のＮ−（５−（４−（イソプロピルアミノ）フェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）ベンズアミド塩酸塩37mgを得た。
1H-NMR(CD3OD)δ値：1.39(6H,d,J=6.6Hz),3.09(3H,s),3.34(3H,s),3.78-3.90(1H,m),7.52-7.66(6H,m),7.72(1H,d,J=8.3Hz),7.89-7.95(2H,m),7.95-8.00(2H,m),8.53(1H,d,J=2.0Hz).Example 289
To the obtained N- (5- (4- (isopropylamino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl) benzamide was added 1 mL of ethyl acetate and 0.037 mL of 4 mol / L hydrogen chloride-dioxane solution, and the pressure was reduced. The solvent was distilled off under. Diisopropyl ether and ethyl acetate were added to the obtained residue, the solid was collected by filtration, and white solid N- (5- (4- (isopropylamino) phenyl) -2- (methyl (methylsulfonyl) amino) phenyl ) 37 mg of benzamide hydrochloride was obtained.
1 H-NMR (CD 3 OD) δ value: 1.39 (6H, d, J = 6.6 Hz), 3.09 (3H, s), 3.34 (3H, s), 3.78-3.90 (1H, m), 7.52-7.66 (6H, m), 7.72 (1H, d, J = 8.3Hz), 7.89-7.95 (2H, m), 7.95-8.00 (2H, m), 8.53 (1H, d, J = 2.0Hz).
実施例２９０
２−メトキシ−Ｎ−（２−（メチル（メチルスルホニル）アミノ）−５−（１Ｈ−ピロロ［２，３−ｂ］ピリジン−５−イル）フェニル）ベンズアミド
1H-NMR(DMSO-d6)δ値：3.19(3H,s),3.31(3H,s),4.12(3H,s),6.54-6.59(1H,m),7.17(1H,dd,J=7.6,7.6Hz),7.30(1H,d,J=8.3Hz),7.53-7.59(2H,m),7.59-7.66(1H,m),7.76(1H,d,J=8.3Hz),8.13-8.18(1H,m),8.22-8.26(1H,m),8.54(1H,d,J=2.0Hz),8.94(1H,d,J=1.7Hz),10.85(1H,s),11.80(1H,s).Example 290
2-Methoxy-N- (2- (methyl (methylsulfonyl) amino) -5- (1H-pyrrolo [2,3-b] pyridin-5-yl) phenyl) benzamide
1 H-NMR (DMSO-d 6 ) δ value: 3.19 (3H, s), 3.31 (3H, s), 4.12 (3H, s), 6.54-6.59 (1H, m), 7.17 (1H, dd, J = 7.6,7.6Hz), 7.30 (1H, d, J = 8.3Hz), 7.53-7.59 (2H, m), 7.59-7.66 (1H, m), 7.76 (1H, d, J = 8.3Hz), 8.13 -8.18 (1H, m), 8.22-8.26 (1H, m), 8.54 (1H, d, J = 2.0Hz), 8.94 (1H, d, J = 1.7Hz), 10.85 (1H, s), 11.80 ( 1H, s).
実施例２９１
得られたｔｅｒｔ−ブチル＝４−（３−（２−メトキシベンズアミド）−４−（メチル（メチルスルホニル）アミノ）フェニル）フェニルカルバマートにトリフルオロ酢酸2mLを加え、室温で30分間攪拌した。減圧下で溶媒を留去し、飽和炭酸水素ナトリウム水溶液および酢酸エチルを加えた。有機層を分取し、飽和塩化ナトリウム水溶液で洗浄後、無水硫酸マグネシウムで乾燥させ、減圧下で溶媒を留去した。得られた残留物にジイソプロピルエーテルを加え、固形物をろ取し、白色固体のＮ−（５−（４−アミノフェニル）−２−（メチル（メチルスルホニル）アミノ）フェニル）−２−メトキシベンズアミド60mgを得た。
1H-NMR(DMSO-d6)δ値：3.15(3H,s),3.27(3H,s),4.10(3H,s),5.27-5.38(2H,broad),6.68(2H,d,J=8.5Hz),7.16(1H,dd,J=7.6,7.6Hz),7.29(1H,d,J=8.1Hz),7.33-7.43(3H,m),7.57-7.66(2H,m),8.14(1H,dd,J=7.9,1.8Hz),8.77(1H,d,J=2.2Hz),10.76(1H,s).Example 291
To the obtained tert-butyl = 4- (3- (2-methoxybenzamido) -4- (methyl (methylsulfonyl) amino) phenyl) phenylcarbamate, 2 mL of trifluoroacetic acid was added and stirred at room temperature for 30 minutes. The solvent was distilled off under reduced pressure, and a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate were added. The organic layer was separated, washed with a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Diisopropyl ether was added to the obtained residue, and the solid was collected by filtration to give N- (5- (4-aminophenyl) -2- (methyl (methylsulfonyl) amino) phenyl) -2-methoxybenzamide as a white solid. 60 mg was obtained.
1 H-NMR (DMSO-d 6 ) δ value: 3.15 (3H, s), 3.27 (3H, s), 4.10 (3H, s), 5.27-5.38 (2H, broad), 6.68 (2H, d, J = 8.5Hz), 7.16 (1H, dd, J = 7.6,7.6Hz), 7.29 (1H, d, J = 8.1Hz), 7.33-7.43 (3H, m), 7.57-7.66 (2H, m), 8.14 (1H, dd, J = 7.9,1.8Hz), 8.77 (1H, d, J = 2.2Hz), 10.76 (1H, s).
実施例２９２
1H-NMR(CDCl3)δ値：2.87(3H,s),5.11(2H,s),7.00(1H,s),7.05(1H,s),7.22-7.45(8H,m),7.47-7.54(2H,m),7.55-7.61(3H,m),7.65(1H,s),7.90-7.95(2H,m),8.48(1H,s).Example 292
1 H-NMR (CDCl 3 ) δ value: 2.87 (3H, s), 5.11 (2H, s), 7.00 (1H, s), 7.05 (1H, s), 7.22-7.45 (8H, m), 7.47- 7.54 (2H, m), 7.55-7.61 (3H, m), 7.65 (1H, s), 7.90-7.95 (2H, m), 8.48 (1H, s).
実施例２９３
1H-NMR(DMSO-d6)δ値：2.99(3H,s),7.12(1H,s),7.27-7.34(1H,m),7.37-7.45(2H,m),7.47(1H,s),7.51-7.64(5H,m),7.94-8.00(2H,m),9.07(1H,s),9.72(1H,s),9.85(1H,s).Example 293
1 H-NMR (DMSO-d 6 ) δ value: 2.99 (3H, s), 7.12 (1H, s), 7.27-7.34 (1H, m), 7.37-7.45 (2H, m), 7.47 (1H, s) ), 7.51-7.64 (5H, m), 7.94-8.00 (2H, m), 9.07 (1H, s), 9.72 (1H, s), 9.85 (1H, s).
実施例２９４
1H-NMR(CDCl3)δ値：2.70(3H,s),3.20(3H,s),5.06(2H,s),6.75(1H,s),7.24-7.58(11H,m),7.63-7.69(2H,m),7.92-7.98(2H,m),8.35(1H,s),9.07(1H,s).Example 294
1 H-NMR (CDCl 3 ) δ value: 2.70 (3H, s), 3.20 (3H, s), 5.06 (2H, s), 6.75 (1H, s), 7.24-7.58 (11H, m), 7.63 7.69 (2H, m), 7.92-7.98 (2H, m), 8.35 (1H, s), 9.07 (1H, s).
実施例２９５
1H-NMR(DMSO-d6)δ値：3.09(3H,s),3.19(3H,s),7.06(1H,s),7.31-7.37(1H,m),7.40-7.47(2H,m),7.51-7.63(5H,m),7.71(1H,s),7.87-7.95(2H,m),9.49(1H,s),9.85(1H,s).Example 295
1 H-NMR (DMSO-d 6 ) δ value: 3.09 (3H, s), 3.19 (3H, s), 7.06 (1H, s), 7.31-7.37 (1H, m), 7.40-7.47 (2H, m ), 7.51-7.63 (5H, m), 7.71 (1H, s), 7.87-7.95 (2H, m), 9.49 (1H, s), 9.85 (1H, s).
実施例２９６
1H-NMR(DMSO-d6)δ値：2.96(6H,s),3.09(3H,s),3.22(3H,s),6.81-6.88(2H,m),7.30(1H,t,J=73.0Hz),7.36-7.57(5H,m),7.60-7.69(2H,m),7.88-7.94(1H,m),8.45-8.52(1H,m),9.73(1H,s).Example 296
1 H-NMR (DMSO-d 6 ) δ value: 2.96 (6H, s), 3.09 (3H, s), 3.22 (3H, s), 6.81-6.88 (2H, m), 7.30 (1H, t, J = 73.0Hz), 7.36-7.57 (5H, m), 7.60-7.69 (2H, m), 7.88-7.94 (1H, m), 8.45-8.52 (1H, m), 9.73 (1H, s).
本発明の化合物およびその塩は、強いＰＧＥ２産生阻害作用を有することから、炎症性疾患の治療あるいは予防などの処置ならびにＰＧＥ２の関与する疾患または状態の治療あるいは予防などの処置に有用である。Since the compounds of the present invention and salts thereof have a strong PGE 2 production inhibitory action, they are useful for treatments such as treatment or prevention of inflammatory diseases and treatments such as treatment or prevention of diseases or conditions involving PGE 2. .
Claims (9)
Ｒ１は、水素原子または置換されていてもよいアルキル、アルケニル、アルキニルもしくはシクロアルキル基を；
Ｒ２は、置換されていてもよいアルキル、アルケニル、アルキニル、シクロアルキル、シクロアルケニル、アリール、アルアルキル、複素環式または複素環式アルキル基を；
Ｒ３は、置換されていてもよいシクロアルキル、シクロアルケニル、アリールまたは複素環式基を；
Ｒ４は、置換されていてもよいシクロアルキル、シクロアルケニル、アリールまたは複素環式基を；
Ｒ５は、水素原子、ハロゲン原子、ヒドロキシル基、アルキル基またはアルコキシ基を；
Ｘ１は、置換されていてもよいアルキレン、アルケニレン、アルキニレンもしくはシクロアルキレン基または結合手を；
Ｘ２は、酸素原子、硫黄原子、保護されていてもよいイミノ基または結合手を；
Ｙ１は、保護されていてもよいイミノ基、置換されていてもよいアルキレン、アルケニレンもしくはアルキニレン基または結合手を；
Ｚ１は、窒素原子またはＣＲ６「式中、Ｒ６は、水素原子、ハロゲン原子、シアノ基、保護されていてもよいヒドロキシル基または置換されていてもよいアルキルもしくはアルコキシ基を示す。」で表される基を；
Ｚ２は、窒素原子またはＣＲ７「式中、Ｒ７は、水素原子、ハロゲン原子、シアノ基、保護されていてもよいヒドロキシル基または置換されていてもよいアルキルもしくはアルコキシ基を示す。」で表される基（但し、Ｚ２がＣＲ７のとき、Ｒ１およびＲ７は、一緒になって、置換されていてもよいＣ２−４アルキレンまたはＣ２−４アルケニレン基であってもよい。）を示し、
上記において、
Ｒ１のアルキル基、アルケニル基、アルキニル基およびシクロアルキル基の置換基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、スルホ基、ホスホリル基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基、ハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、シクロアルキル、シクロアルケニル、アリール、環状アミノ、アルアルキルおよび複素環式基ならびにオキソ基から選ばれる１つ以上の基を示し、
Ｒ２のアルキル基、アルケニル基、アルキニル基、シクロアルキル基、シクロアルケニル基、アリール基、アルアルキル基、複素環式基および複素環式アルキル基の置換基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、アシルオキシ基、スルホ基、ホスホリル基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基、ハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、シクロアルキル、シクロアルケニル、アリール、環状アミノ、アルアルキルおよび複素環式基ならびにオキソ基から選ばれる１つ以上の基を示し、
Ｒ３のシクロアルキル基、シクロアルケニル基、アリール基および複素環式基の置換基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、アシルオキシ基、スルホ基、ホスホリル基、アルキルチオ基、アルキルアミノ基、ジアルキルアミノ基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、ヒドロキシアルキル基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基、保護されていてもよいカルボキシル基で置換されているアルコキシ基、ハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、シクロアルキル、シクロアルケニル、アリール、アリールオキシ、環状アミノ、アルアルキルおよび複素環式基ならびにオキソ基から選ばれる１つ以上の基を示し、
Ｒ４のシクロアルキル基、シクロアルケニル基、アリール基および複素環式基の置換基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、アシルオキシ基、スルホ基、ホスホリル基、アルキルチオ基、ジアルキルアミノ基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、ヒドロキシアルキル基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいアルキルアミノ基、保護されていてもよいヒドロキシル基、保護されていてもよいカルボキシル基で置換されているアルコキシ基、ハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、シクロアルキル、シクロアルケニル、アリール、アリールオキシ、環状アミノ、アルアルキルおよび複素環式基ならびにオキソ基から選ばれる１つ以上の基を示し、
Ｘ１のアルキレン基、アルケニレン基、アルキニレン基およびシクロアルキレン基の置換基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、スルホ基、ホスホリル基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基ならびにハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、アリール、環状アミノ、アルアルキルおよび複素環式基から選ばれる１つ以上の基を示し、
Ｙ１のアルキレン基、アルケニレン基およびアルキニレン基の置換基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、スルホ基、ホスホリル基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基ならびにハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、アリール、環状アミノ、アルアルキルおよび複素環式基から選ばれる１つ以上の基を示し、
Ｒ６およびＲ７のアルキル基およびアルコキシ基の置換基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、スルホ基、ホスホリル基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基ならびにハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、アリール、環状アミノ、アルアルキルおよび複素環式基から選ばれる１つ以上の基を示し、
Ｒ１およびＲ７が、一緒になって形成されるＣ２−４アルキレン基およびＣ２−４アルケニレン基の置換基は、ハロゲン原子、シアノ基、ニトロ基、アシル基、スルホ基、ホスホリル基、アルキルスルホニル基、アルキルスルホニルアミノ基、アルカノイルアミノ基、カルバモイル基、保護されていてもよいカルボキシル基、保護されていてもよいアミノ基、保護されていてもよいヒドロキシル基ならびにハロゲン原子で置換されていてもよいアルキル、アルケニル、アルキニル、アルコキシ、アリール、環状アミノ、アルアルキルおよび複素環式基から選ばれる１つ以上の基を示し、
フェノール性ヒドロキシル基の保護基は、アシル基、アルキル基、アルケニル基、アルアルキル基、含酸素複素環式基、含硫黄複素環式基、アルコキシアルキル基、アルキルスルホニル基、アリールスルホニル基または置換シリル基を示し、
イミノ基の保護基は、アシル基、アルキルオキシカルボニル基、アルアルキルオキシカルボニル基、アリールオキシカルボニル基、アルアルキル基、アルコキシアルキル基、アリールチオ基、アルキルスルホニル基、アリールスルホニル基または置換シリル基を示し、
カルボキシル基の保護基は、アルキル基、アリール基、アルアルキル基、アシルアルキル基、アリールチオアルキル基、アリールスルホニルアルキル基、含酸素複素環式基、アルキルシリルアルキル基、アシルオキシアルキル基、含窒素複素環式アルキル基、シクロアルキル基、アルコキシアルキル基、アルアルキルオキシアルキル基、アルキルチオアルキル基、アルケニル基または置換シリル基を示し、
アミノ基の保護基は、アシル基、アルキルオキシカルボニル基、アルアルキルオキシカルボニル基、アリールオキシカルボニル基、アルアルキル基、アルコキシアルキル基、アルアルキルオキシアルキル基、アリールチオ基、アルキルスルホニル基、アリールスルホニル基または置換シリル基を示し、
アルキルアミノ基の保護基は、アシル基、アルキルオキシカルボニル基、アルアルキルオキシカルボニル基、アリールオキシカルボニル基、アルアルキル基、アルコキシアルキル基、アリールチオ基、アルキルスルホニル基、アリールスルホニル基または置換シリル基を示し、
ヒドロキシル基の保護基は、アシル基、アルキル基、アルケニル基、アルアルキル基、含酸素複素環式基、含硫黄複素環式基、アルコキシアルキル基、アルキルスルホニル基、アリールスルホニル基または置換シリル基を示す。」で表される化合物またはその塩。 General formula
R 1 represents a hydrogen atom or an optionally substituted alkyl, alkenyl, alkynyl or cycloalkyl group;
R 2 represents an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, aralkyl, heterocyclic or heterocyclic alkyl group;
R 3 represents an optionally substituted cycloalkyl, cycloalkenyl, aryl or heterocyclic group;
R 4 represents an optionally substituted cycloalkyl, cycloalkenyl, aryl or heterocyclic group;
R 5 represents a hydrogen atom, a halogen atom, a hydroxyl group, an alkyl group or an alkoxy group ;
X 1 represents an optionally substituted alkylene, alkenylene, alkynylene or cycloalkylene group or a bond;
X 2 represents an oxygen atom, a sulfur atom, an optionally protected imino group or a bond;
Y 1 represents an optionally protected imino group, an optionally substituted alkylene, alkenylene or alkynylene group or a bond;
Z 1 is a nitrogen atom or CR 6 , wherein R 6 represents a hydrogen atom, a halogen atom, a cyano group, an optionally protected hydroxyl group, or an optionally substituted alkyl or alkoxy group. The group represented;
Z 2 represents a nitrogen atom or CR 7 , wherein R 7 represents a hydrogen atom, a halogen atom, a cyano group, an optionally protected hydroxyl group, or an optionally substituted alkyl or alkoxy group. A group represented by the formula (provided that when Z 2 is CR 7 , R 1 and R 7 may together be an optionally substituted C 2-4 alkylene or C 2-4 alkenylene group). )
In the above,
The substituent of the alkyl group, alkenyl group, alkynyl group and cycloalkyl group of R 1 is a halogen atom, cyano group, nitro group, acyl group, sulfo group, phosphoryl group, alkylsulfonyl group, alkylsulfonylamino group, alkanoylamino group , A carbamoyl group, an optionally protected carboxyl group, an optionally protected amino group, an optionally protected hydroxyl group, an alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl optionally substituted with a halogen atom One or more groups selected from cycloalkenyl, aryl, cyclic amino, aralkyl and heterocyclic groups and oxo groups;
The substituent of the alkyl group, alkenyl group, alkynyl group, cycloalkyl group, cycloalkenyl group, aryl group, aralkyl group, heterocyclic group and heterocyclic alkyl group of R 2 is a halogen atom, cyano group, nitro group , Acyl group, acyloxy group, sulfo group, phosphoryl group, alkylsulfonyl group, alkylsulfonylamino group, alkanoylamino group, carbamoyl group, optionally protected carboxyl group, optionally protected amino group, protected One or more selected from an optionally substituted hydroxyl group, an optionally substituted alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, aryl, cyclic amino, aralkyl and heterocyclic group and an oxo group The group of
Substituents for the cycloalkyl group, cycloalkenyl group, aryl group and heterocyclic group of R 3 are halogen atom, cyano group, nitro group, acyl group, acyloxy group, sulfo group, phosphoryl group, alkylthio group, alkylamino group , Dialkylamino group, alkylsulfonyl group, alkylsulfonylamino group, alkanoylamino group, hydroxyalkyl group, carbamoyl group, optionally protected carboxyl group, optionally protected amino group, optionally protected hydroxyl group Group, alkoxy group substituted by an optionally protected carboxyl group, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, aryl, aryloxy, cyclic amino, alkyl optionally substituted by a halogen atom Alkyl and One or more groups selected from a heterocyclic group and an oxo group;
Substituents for the cycloalkyl group, cycloalkenyl group, aryl group and heterocyclic group of R 4 are halogen atom, cyano group, nitro group, acyl group, acyloxy group, sulfo group, phosphoryl group, alkylthio group, dialkylamino group , Alkylsulfonyl group, alkylsulfonylamino group, alkanoylamino group, hydroxyalkyl group, carbamoyl group, optionally protected carboxyl group, optionally protected amino group, optionally protected alkylamino group, protection An optionally substituted hydroxyl group, an alkoxy group substituted with an optionally protected carboxyl group, an alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, aryl, aryl optionally substituted with a halogen atom Oxy, cyclic amino One or more groups selected from aralkyl and heterocyclic groups and oxo groups ;
Substituents for the alkylene group, alkenylene group, alkynylene group and cycloalkylene group of X 1 are a halogen atom, cyano group, nitro group, acyl group, sulfo group, phosphoryl group, alkylsulfonyl group, alkylsulfonylamino group, alkanoylamino group , A carbamoyl group, an optionally protected carboxyl group, an optionally protected amino group, an optionally protected hydroxyl group, and an alkyl, alkenyl, alkynyl, alkoxy, aryl, optionally substituted with a halogen atom, One or more groups selected from cyclic amino, aralkyl and heterocyclic groups,
The substituent for the alkylene group, alkenylene group and alkynylene group of Y 1 is a halogen atom, a cyano group, a nitro group, an acyl group, a sulfo group, a phosphoryl group, an alkylsulfonyl group, an alkylsulfonylamino group, an alkanoylamino group, a carbamoyl group, An optionally protected carboxyl group, an optionally protected amino group, an optionally protected hydroxyl group, and an alkyl, alkenyl, alkynyl, alkoxy, aryl, cyclic amino, alkyl optionally substituted with a halogen atom One or more groups selected from alkyl and heterocyclic groups;
Substituents for the alkyl group and alkoxy group of R 6 and R 7 are halogen atom, cyano group, nitro group, acyl group, sulfo group, phosphoryl group, alkylsulfonyl group, alkylsulfonylamino group, alkanoylamino group, carbamoyl group, An optionally protected carboxyl group, an optionally protected amino group, an optionally protected hydroxyl group, and an alkyl, alkenyl, alkynyl, alkoxy, aryl, cyclic amino, alkyl optionally substituted with a halogen atom One or more groups selected from alkyl and heterocyclic groups;
The substituents of the C 2-4 alkylene group and the C 2-4 alkenylene group formed by R 1 and R 7 being taken together are a halogen atom, a cyano group, a nitro group, an acyl group, a sulfo group, a phosphoryl group, Substituted with an alkylsulfonyl group, an alkylsulfonylamino group, an alkanoylamino group, a carbamoyl group, an optionally protected carboxyl group, an optionally protected amino group, an optionally protected hydroxyl group, and a halogen atom; Represents one or more groups selected from alkyl, alkenyl, alkynyl, alkoxy, aryl, cyclic amino, aralkyl and heterocyclic groups,
The protecting group for the phenolic hydroxyl group is an acyl group, alkyl group, alkenyl group, aralkyl group, oxygen-containing heterocyclic group, sulfur-containing heterocyclic group, alkoxyalkyl group, alkylsulfonyl group, arylsulfonyl group or substituted silyl group. Group,
The protecting group for the imino group represents an acyl group, an alkyloxycarbonyl group, an aralkyloxycarbonyl group, an aryloxycarbonyl group, an aralkyl group, an alkoxyalkyl group, an arylthio group, an alkylsulfonyl group, an arylsulfonyl group, or a substituted silyl group. ,
The protective group for the carboxyl group is an alkyl group, aryl group, aralkyl group, acylalkyl group, arylthioalkyl group, arylsulfonylalkyl group, oxygen-containing heterocyclic group, alkylsilylalkyl group, acyloxyalkyl group, nitrogen-containing hetero group. A cyclic alkyl group, a cycloalkyl group, an alkoxyalkyl group, an aralkyloxyalkyl group, an alkylthioalkyl group, an alkenyl group or a substituted silyl group;
Protecting group for amino group is acyl group, alkyloxycarbonyl group, aralkyloxycarbonyl group, aryloxycarbonyl group, aralkyl group, alkoxyalkyl group, aralkyloxyalkyl group, arylthio group, alkylsulfonyl group, arylsulfonyl group Or a substituted silyl group,
The protecting group for the alkylamino group includes an acyl group, an alkyloxycarbonyl group, an aralkyloxycarbonyl group, an aryloxycarbonyl group, an aralkyl group, an alkoxyalkyl group, an arylthio group, an alkylsulfonyl group, an arylsulfonyl group, or a substituted silyl group. Show
The protecting group for the hydroxyl group includes an acyl group, an alkyl group, an alkenyl group, an aralkyl group, an oxygen-containing heterocyclic group, a sulfur-containing heterocyclic group, an alkoxyalkyl group, an alkylsulfonyl group, an arylsulfonyl group, or a substituted silyl group. Show. Or a salt thereof.
ここで、Ｒ１およびＲ２のアルキル基の置換基は、請求項１と同様である、請求項１記載の化合物またはその塩。 R 1 is an optionally substituted C 1-6 alkyl group, R 2 is an optionally substituted C 1-6 alkyl group,
Wherein the substituents of the alkyl group of R 1 and R 2 are the same as defined in Claim 1, or a salt thereof according to claim 1, wherein.
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| CN103209960A (en) | 2010-07-26 | 2013-07-17 | 百时美施贵宝公司 | Sulfonamide compounds useful as CYP17 inhibitors |
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| CN114957132A (en) * | 2021-02-20 | 2022-08-30 | 中国科学院上海药物研究所 | S-configuration-containing aminobenzamide pyridazinone compound, preparation method thereof, pharmaceutical composition and application |
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