JPS6257624B2 - - Google Patents
Info
- Publication number
- JPS6257624B2 JPS6257624B2 JP9788078A JP9788078A JPS6257624B2 JP S6257624 B2 JPS6257624 B2 JP S6257624B2 JP 9788078 A JP9788078 A JP 9788078A JP 9788078 A JP9788078 A JP 9788078A JP S6257624 B2 JPS6257624 B2 JP S6257624B2
- Authority
- JP
- Japan
- Prior art keywords
- piperidinyl
- hydrochloride
- group
- melting point
- hydrouracil
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 238000002844 melting Methods 0.000 description 15
- 230000008018 melting Effects 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- -1 etc.) Chemical group 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- YUBDLZGUSSWQSS-UHFFFAOYSA-N 1-benzylpiperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=CC=C1 YUBDLZGUSSWQSS-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 2
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000006264 debenzylation reaction Methods 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 2
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- ZSSBYOXGEIGBLA-UHFFFAOYSA-N 3-phenylpropa-1,2-dienylbenzene Chemical group C=1C=CC=CC=1C=C=CC1=CC=CC=C1 ZSSBYOXGEIGBLA-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 150000002148 esters Chemical group 0.000 description 1
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
Landscapes
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
【発明の詳細な説明】
本発明は、一般式
で表わされる新規な４位に異項環を有するピペリ
ジン類またはその塩類に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the general formula The present invention relates to a novel piperidine having a heterocyclic ring at the 4-position represented by the above formula or a salt thereof.
上記式中、R1は水素またはメチル基を、R2は
水素、低級アルキル（メチル、エチル、プロピ
ル、イソプロピル、ブチルなど）、またはフエニ
ル基を、Ｘは直鎖または分枝の低級アルキレン基
（メチレン、エチレン、エチリデン、トリメチレ
ン、プロピレン、プロピリデン、イソプロピリデ
ンなど）またはフエニル置換低級アルキレン基
（ベンジリデン、フエニルエチレンなど）を示
す。 In the above formula, R 1 is hydrogen or a methyl group, R 2 is hydrogen, lower alkyl (methyl, ethyl, propyl, isopropyl, butyl, etc.), or phenyl group, and X is a linear or branched lower alkylene group ( methylene, ethylene, ethylidene, trimethylene, propylene, propylidene, isopropylidene, etc.) or a phenyl-substituted lower alkylene group (benzylidene, phenylethylene, etc.).
一般式（）の化合物は、一般式
〔式中、R1、R2、Ｘは前記と同義である。〕
で表わされる化合物を脱ベンジルすることにより
製造される。 The compound of the general formula () is the compound of the general formula [In the formula, R 1 , R 2 and X have the same meanings as above. ] It is produced by debenzylizing the compound represented by.
この反応は、通常、不活性溶媒（水、メタノー
ル、エタノール、イソプロパノール、ベンゼン、
トルエン、キシレン、イソプロピルエーテル、テ
トラヒドロフラン、ジオキサン、酢酸、塩酸な
ど、またはこれらの混合溶媒）中、パラジウム−
炭素、酸化白金、ラネ−ニツケルなどの触媒を用
いて、常圧または加圧下に、室温ないし必要に応
じて100℃程度まで加温下に、水素添加すること
により行なわれる。 This reaction is usually carried out in an inert solvent (water, methanol, ethanol, isopropanol, benzene,
Palladium-
Hydrogenation is carried out using a catalyst such as carbon, platinum oxide, Raney-nickel, etc., under normal pressure or increased pressure, and while heating from room temperature to about 100° C. if necessary.
一般式（）の原料化合物は、たとえば次の反
応式で示される、それ自体は公知の方法で容易に
調製される。 The starting compound of general formula () is easily prepared by a method known per se, for example as shown in the following reaction formula.
Ａ：
〔式中、R1、R2は前記と同義であり、R3は水素ま
たは低級アルキル基を、R4は水素、低級アルキ
ル基またはフエニル基を、R5は低級アルキル基
を示す。〕
Ｂ：
〔式中、R1、R2、R4、R5は前記と同義である。〕
一般式（）の化合物は、塩酸塩、臭化水素酸
塩、硫酸塩などの無機酸塩、修酸塩、マレイン酸
塩、フマール酸塩、酒石酸塩、クエン酸塩、安息
香酸塩、サリチル酸塩、メタンスルホン酸塩、ベ
ンゼンスルホン酸塩などの有機酸塩とすることが
できる。A: [In the formula, R 1 and R 2 have the same meanings as above, R 3 represents hydrogen or a lower alkyl group, R 4 represents hydrogen, a lower alkyl group or a phenyl group, and R 5 represents a lower alkyl group. ] B: [In the formula, R 1 , R 2 , R 4 and R 5 have the same meanings as above. ] Compounds of general formula () include inorganic acid salts such as hydrochloride, hydrobromide, and sulfate, oxalate, maleate, fumarate, tartrate, citrate, benzoate, and salicylic acid. It can be an organic acid salt such as a salt, methanesulfonate, or benzenesulfonate.
一般式（）の化合物は、鎮痛剤、消炎剤、向
精神剤、循環器用薬剤を中間体として有用であ
る。たとえば、一般式（）の化合物に、一般式
Ｒ−Ｚ−Ａ−Ｙ （）
〔式中、Ｒは置換または非置換のフエニル基（置
換基としては同一または異なる１〜２個の水酸
基、低級アルコキシ、ハロゲン、低級アルキル、
ヒドロキシ低級アルキル、アシルアミノ低級アル
キル、アラルキルオキシ、フエノキシ低級アルコ
キシである）、チエニル基、置換または非置換の
ベンゾフラニル基または２・３−ジヒドロベンゾ
フラニル基（置換基としては同一または異なる１
〜２個の低級アルキル、低級アルコキシ、ハロゲ
ンである）、低級アルキル基、シクロアルキル基
またはアラルキル基を、Ｚは−Ｃ≡Ｃ−、−CH＝
CH−、−CO−、−CH（OH）−、−NH−、−Ｎ
（Ac）−〔Acはアシルである〕、−CH（CN）−、−Ｏ
−または単結合を、Ａは低級アルキレン基または
ベンジリデン基を、Ｙは前記の如き活性エステル
残基を示す。〕
で表わされる化合物を作用させることにより、鎮
痛剤、抗炎症剤として有用な、一般式
〔式中、各記号は前記と同義である。〕
で表わされる化合物に導くことができる。 The compound of general formula () is useful as an intermediate for analgesics, anti-inflammatory agents, psychotropic agents, and cardiovascular drugs. For example, in the compound of the general formula (), the compound of the general formula alkoxy, halogen, lower alkyl,
hydroxy lower alkyl, acylamino lower alkyl, aralkyloxy, phenoxy lower alkoxy), thienyl group, substituted or unsubstituted benzofuranyl group or 2,3-dihydrobenzofuranyl group (same or different substituents)
~2 lower alkyl, lower alkoxy, halogen), lower alkyl group, cycloalkyl group or aralkyl group, Z is -C≡C-, -CH=
CH-, -CO-, -CH(OH)-, -NH-, -N
(Ac)-[Ac is acyl], -CH(CN)-, -O
- or a single bond, A represents a lower alkylene group or benzylidene group, and Y represents an active ester residue as described above. ] By acting on the compound represented by the general formula [In the formula, each symbol has the same meaning as above. ] This can lead to a compound represented by
以下実施例により本発明をより一層具体的に説
明する。 The present invention will be explained in more detail below using Examples.
実施例 １
４−アミノ−１−ベンジルピペリジン19ｇ、ア
クリル酸エチル10ｇをエタノール100ml中で２時
間還流させる。これを冷却し、メチルイソシアナ
ート5.7ｇを10〜30℃で加え、２時間室温で放置
後、過剰の塩化水素ガスを吹きこみ、１時間還流
させる。冷却すると、融点274℃の白色結晶とし
て、１−（１−ベンジル−４−ピペリジニル）−３
−メチル−ヒドロウラシル・塩酸塩が28ｇ得られ
る。本品を85％エタノール250ml中、５％パラジ
ウム炭素４ｇを用い、常圧、室温で水添脱ベンジ
ル化を行う。反応完了後、触媒を去し、溶媒を
留去すると、融点253℃の１−（４−ピペリジニ
ル）−３−メチル−ヒドロウラシル・塩酸塩が18
ｇ得られる。Example 1 19 g of 4-amino-1-benzylpiperidine and 10 g of ethyl acrylate are refluxed in 100 ml of ethanol for 2 hours. This was cooled, 5.7 g of methyl isocyanate was added at 10 to 30°C, and after being left at room temperature for 2 hours, excess hydrogen chloride gas was blown into the mixture and the mixture was refluxed for 1 hour. Upon cooling, 1-(1-benzyl-4-piperidinyl)-3 forms as white crystals with a melting point of 274°C.
28 g of -methyl-hydrouracil hydrochloride is obtained. This product is hydrogenated and debenzylated using 4 g of 5% palladium on carbon in 250 ml of 85% ethanol at normal pressure and room temperature. After the reaction is completed, the catalyst is removed and the solvent is distilled off to give 1-(4-piperidinyl)-3-methyl-hydrouracil hydrochloride with a melting point of 253°C.
g can be obtained.
実施例１と同様にして、次の化合物が得られ
る。 In the same manner as in Example 1, the following compound is obtained.
◎１−（４−ピペリジニル）−３−フエニル−ヒド
ロウラシル・塩酸塩、融点253℃
◎１−（４−ピペリジニル）−３・５−ジメチル−
ヒドロウラシル・塩酸塩、融点266℃
◎１−（４−ピペリジニル）−３−メチル−５−フ
エニル−ヒドロウラシル・塩酸塩、融点241℃
◎１−（４−ピペリジニル）−３−フエニル−５−
メチル−ヒドロウラシル・塩酸塩、融点251℃
◎１−（４−ピペリジニル）−３・６−ジメチル−
ヒドロウラシル・塩酸塩、融点273℃
◎１−（４−ピペリジニル）−３−エチル−ヒドロ
ウラシル・マレイン酸塩、融点117℃
◎１−（４−ピペリジニル）−３−プロピル−ヒド
ロウラシル・塩酸塩、融点281℃
◎１−（４−ピペリジニル）−３−ブチル−ヒドロ
ウラシル・塩酸塩、融点267℃
◎１−（４−ピペリジニル）−３−イソプロピル−
ヒドロウラシル・塩酸塩、
◎１−（３−メチル−４−ピペリジニル）−３−メ
チル−ヒドロウラシル 塩酸塩、融点290℃
実施例 ２
４−アミノ−１−ベンジルピペリジンとアクリ
ル酸エチルとを実施例１と同様に反応させて得ら
れる３−（１−ベンジル−４−ピペリジニルアミ
ノ）プロピオン酸エチル28ｇを80％酢酸85mlにと
かし、イソシアン酸カリウム14ｇを10〜20℃で加
える。室温で一夜放置後、５時間還流させる。反
応液を濃縮し、残査を水80mlにとかし、炭酸ナト
リウムで中和する。析出する結晶を取し、メタ
ノールから再結晶すると、融点207℃の白色結晶
として、１−（１−ベンジル−４−ピペリジニ
ル）ヒドロウラシルが16ｇ得られる。◎1-(4-piperidinyl)-3-phenyl-hydrouracil hydrochloride, melting point 253℃ ◎1-(4-piperidinyl)-3,5-dimethyl-
Hydrouracil hydrochloride, melting point 266℃ ◎1-(4-piperidinyl)-3-methyl-5-phenyl-hydrouracil hydrochloride, melting point 241℃ ◎1-(4-piperidinyl)-3-phenyl-5-
Methyl-hydrouracil hydrochloride, melting point 251℃ ◎1-(4-piperidinyl)-3,6-dimethyl-
Hydrouracil hydrochloride, melting point 273℃ ◎1-(4-piperidinyl)-3-ethyl-hydrouracil maleate, melting point 117℃ ◎1-(4-piperidinyl)-3-propyl-hydrouracil hydrochloride , melting point 281℃ ◎1-(4-piperidinyl)-3-butyl-hydrouracil hydrochloride, melting point 267℃ ◎1-(4-piperidinyl)-3-isopropyl-
Hydrouracil hydrochloride, ◎1-(3-methyl-4-piperidinyl)-3-methyl-hydrouracil hydrochloride, melting point 290°C Example 2 Example of 4-amino-1-benzylpiperidine and ethyl acrylate 28 g of ethyl 3-(1-benzyl-4-piperidinylamino)propionate obtained by the same reaction as in 1 is dissolved in 85 ml of 80% acetic acid, and 14 g of potassium isocyanate is added at 10 to 20°C. After standing overnight at room temperature, reflux for 5 hours. Concentrate the reaction solution, dissolve the residue in 80 ml of water, and neutralize with sodium carbonate. The precipitated crystals are collected and recrystallized from methanol to obtain 16 g of 1-(1-benzyl-4-piperidinyl)hydrouracil as white crystals with a melting point of 207°C.
本品を２％塩酸100mlにとかし、５％パラジウ
ム炭素３ｇを用い、常圧、室温で水添脱ベンジル
化を行う。反応完了後、触媒を去し、液を濃
縮すると、融点300℃以上の結晶として、１−（４
−ピペリジニル）ヒドロウラシル・塩酸塩が収率
95％で得られる。 Dissolve this product in 100 ml of 2% hydrochloric acid and perform hydrogen debenzylation using 3 g of 5% palladium on carbon at normal pressure and room temperature. After the reaction is completed, the catalyst is removed and the liquid is concentrated to form 1-(4
-Piperidinyl)hydrouracil hydrochloride yield
Obtained at 95%.
実施例 ３
４−アミノ−１−ベンジルピペリジン19ｇ、２
−ブロムプロピオン酸エチル18ｇ、無水炭酸カリ
ウム20ｇを０〜10℃で混合する。室温で24時間か
きまぜる。炭酸カリウムを去し、液を減圧下
濃縮し、残査に水100mlを加え、酢酸エチル50ml
で３回抽出する。抽出液を無水硫酸マグネシウム
で乾燥し、濃縮すると、粗製の２−（１−ベンジ
ル−４−ピペリジニルアミノ）プロピオン酸エチ
ルが油状物として22ｇが得られる。Example 3 4-amino-1-benzylpiperidine 19g, 2
- Mix 18 g of ethyl bromopropionate and 20 g of anhydrous potassium carbonate at 0-10°C. Stir at room temperature for 24 hours. Potassium carbonate was removed, the liquid was concentrated under reduced pressure, 100 ml of water was added to the residue, and 50 ml of ethyl acetate was added.
Extract 3 times. The extract is dried over anhydrous magnesium sulfate and concentrated to yield 22 g of crude ethyl 2-(1-benzyl-4-piperidinylamino)propionate as an oil.
本品をベンゼン100mlにとかし、氷冷下メチル
イソシアネート7.5ｇを加え、室温で８時間反応
させる。これにアルコール性塩酸を加え、50℃で
２時間加温する。析出する結晶を取し、エタノ
ールから再結晶すると、融点245℃の結晶とし
て、１−（１−ベンジル−４−ピペリジニル）−
３・５−ジメチルヒダントイン・塩酸塩が17ｇ得
られる。 Dissolve this product in 100 ml of benzene, add 7.5 g of methyl isocyanate under ice cooling, and react at room temperature for 8 hours. Add alcoholic hydrochloric acid to this and heat at 50°C for 2 hours. When the precipitated crystals are collected and recrystallized from ethanol, 1-(1-benzyl-4-piperidinyl)-
17 g of 3,5-dimethylhydantoin hydrochloride is obtained.
本品を80％エタノール200ml中、５％パラジウ
ム炭素３ｇを用い、常温常圧下、水添脱ベンジル
反応を行う。反応完了後、触媒を去し、液を
濃縮する。析出する結晶を取し、メタノールか
ら再結晶すると、融点270℃の結晶として、１−
（４−ピペリジニル）−３・５−ジメチル−ヒダン
トイン・塩酸塩が12ｇ得られる。 This product is subjected to a hydrogenation-debenzylation reaction using 3 g of 5% palladium on carbon in 200 ml of 80% ethanol at room temperature and normal pressure. After the reaction is complete, the catalyst is removed and the liquid is concentrated. When the precipitated crystals are collected and recrystallized from methanol, 1-
12 g of (4-piperidinyl)-3,5-dimethyl-hydantoin hydrochloride is obtained.
実施例３と同様にして、次の化合物が得られ
る。 Analogously to Example 3, the following compound is obtained.
◎１−（４−ピペリジニル）−３−メチル−５−フ
エニル−ヒダントイン・塩酸塩、融点242℃
◎１−（４−ピペリジニル）−３−フエニル−５−
メチル−ヒダントイン・塩酸塩、融点300℃
（分解）
◎１−（４−ピペリジニル）−３・５−ジフエニル
−ヒダントイン・塩酸塩、融点268℃
◎１−（４−ピペリジニル）−３・５・５−トリメ
チル−ヒダントイン
◎１−（３−メチル−４−ピペリジニル）−３・５
−ジメチル−ヒダントイン◎1-(4-piperidinyl)-3-methyl-5-phenyl-hydantoin hydrochloride, melting point 242℃ ◎1-(4-piperidinyl)-3-phenyl-5-
Methyl-hydantoin hydrochloride, melting point 300℃
(Decomposition) ◎1-(4-piperidinyl)-3,5-diphenyl-hydantoin hydrochloride, melting point 268℃ ◎1-(4-piperidinyl)-3,5,5-trimethyl-hydantoin ◎1-(3- Methyl-4-piperidinyl)-3.5
-dimethyl-hydantoin
Claims (1)
低級アルキル基またはフエニル基を、Ｘは直鎖ま
たは分枝の低級アルキレン基またはフエニル置換
低級アルキレン基を示す。〕 で表わされる化合物またはその塩類。[Claims] 1. General formula [In the formula, R 1 is hydrogen or a methyl group, R 2 is hydrogen,
X represents a lower alkyl group or a phenyl group, and X represents a linear or branched lower alkylene group or a phenyl-substituted lower alkylene group. ] A compound represented by or its salts.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9788078A JPS5524155A (en) | 1978-08-10 | 1978-08-10 | Piperidine derivative having heterocyclic ring at 4-position |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9788078A JPS5524155A (en) | 1978-08-10 | 1978-08-10 | Piperidine derivative having heterocyclic ring at 4-position |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5524155A JPS5524155A (en) | 1980-02-21 |
| JPS6257624B2 true JPS6257624B2 (en) | 1987-12-02 |
Family
ID=14204050
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9788078A Granted JPS5524155A (en) | 1978-08-10 | 1978-08-10 | Piperidine derivative having heterocyclic ring at 4-position |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5524155A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5753481A (en) * | 1980-09-17 | 1982-03-30 | Yoshitomi Pharmaceut Ind Ltd | 4-hydrouracil-piperidines |
| JPS5996686U (en) * | 1982-12-17 | 1984-06-30 | 富士電機冷機株式会社 | Cup type vending machine |
| JPH07116146B2 (en) * | 1986-12-05 | 1995-12-13 | 広栄化学工業株式会社 | Process for producing 4-piperidinopiperidines |
| JP2807577B2 (en) * | 1990-06-15 | 1998-10-08 | エーザイ株式会社 | Cyclic amide derivative |
-
1978
- 1978-08-10 JP JP9788078A patent/JPS5524155A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5524155A (en) | 1980-02-21 |
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