JPH0216310B2 - - Google Patents
Info
- Publication number
- JPH0216310B2 JPH0216310B2 JP15949681A JP15949681A JPH0216310B2 JP H0216310 B2 JPH0216310 B2 JP H0216310B2 JP 15949681 A JP15949681 A JP 15949681A JP 15949681 A JP15949681 A JP 15949681A JP H0216310 B2 JPH0216310 B2 JP H0216310B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- trioxo
- pyrrolo
- tetrahydro
- pyrimidine
- 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
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 150000004944 pyrrolopyrimidines Chemical class 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- -1 3,6-dimethyl-2-hydroxy-3,4,6,7-tetrahydro- 4,5,7-trioxo-5H-pyrrolo[3,4-d]pyrimidine Chemical compound 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 8
- 238000000354 decomposition reaction Methods 0.000 description 8
- 239000007795 chemical reaction product Substances 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- TUZVMPXGFZSNBG-UHFFFAOYSA-N 3-aminopyrrole-2,5-dione Chemical compound NC1=CC(=O)NC1=O TUZVMPXGFZSNBG-UHFFFAOYSA-N 0.000 description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 229940117389 dichlorobenzene Drugs 0.000 description 2
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- MSMGXWFHBSCQFB-UHFFFAOYSA-N ethyl cyanoformate Chemical compound CCOC(=O)C#N MSMGXWFHBSCQFB-UHFFFAOYSA-N 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- FUQHJLWTRNTWRC-UHFFFAOYSA-N (2,5-dioxopyrrol-3-yl)urea Chemical compound NC(=O)NC1=CC(=O)NC1=O FUQHJLWTRNTWRC-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- NCYLMOVCPMNHEP-UHFFFAOYSA-N 2,2-dimethylpropanediamide Chemical compound NC(=O)C(C)(C)C(N)=O NCYLMOVCPMNHEP-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- HGINADPHJQTSKN-UHFFFAOYSA-N Monoethyl malonic acid Chemical compound CCOC(=O)CC(O)=O HGINADPHJQTSKN-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- SCYOJLAMDVBOAE-UHFFFAOYSA-N ethyl 2,5-dioxopyrrole-3-carboxylate Chemical compound CCOC(=O)C1=CC(=O)NC1=O SCYOJLAMDVBOAE-UHFFFAOYSA-N 0.000 description 1
- DSHWMBCJDOGPTB-UHFFFAOYSA-N ethyl 2-ethoxy-2-iminoacetate Chemical compound CCOC(=N)C(=O)OCC DSHWMBCJDOGPTB-UHFFFAOYSA-N 0.000 description 1
- UVSPVEYCSVXYBB-UHFFFAOYSA-N ethyl 3-amino-3-oxopropanoate Chemical compound CCOC(=O)CC(N)=O UVSPVEYCSVXYBB-UHFFFAOYSA-N 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- ZWXJWAPTSTYSAH-UHFFFAOYSA-N n,n'-dimethylpropanediamide Chemical compound CNC(=O)CC(=O)NC ZWXJWAPTSTYSAH-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 150000003839 salts Chemical group 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Description
この発明は、新規化合物であるピロロピリミジ
ン誘導体に関するものである。さらに詳しくは、
この発明は、
式
〔式中、R1およびR2は、それぞれ、炭素数１〜
４のアルキル基、炭素数２〜４のアルケニル基、
炭素数５〜７のシクロアルキル基、炭素数７〜10
のアラルキル基、または
This invention relates to a new compound, a pyrrolopyrimidine derivative. For more details,
This invention is based on the formula [In the formula, R 1 and R 2 each have 1 to 1 carbon atoms.
4 alkyl group, alkenyl group having 2 to 4 carbon atoms,
Cycloalkyl group having 5 to 7 carbon atoms, 7 to 10 carbon atoms
an aralkyl group, or
【式】（R3は
炭素数１〜４のアルキル基またはハロゲン原子を
示し、ｎは０，１，２または３である。）で表わ
される基を示す。〕で表わされる２―ヒドロキシ
―３，４，６，７―テトラヒドロ―４，５，７―
トリオキソ―5H―ピロロ〔３，４―ｄ〕ピリミ
ジン誘導体である。
この発明のピロロピリミジン誘導体は、農薬、
医薬、さらにはこれらの中間体として有用であ
る。特に、イネ白葉枯れ病に対する農園芸用殺菌
剤として有用である。
以下にピロロピリミジン誘導体の具体例の物性
を示す。
化合物番号 化 合 物 名 融 点（℃）
１ ３，６―ジメチル―２―ヒドロキシ
―３，４，６，７―テトラヒドロ―
４，５，７―トリオキソ―5H―ピ
ロロ〔３，４―ｄ〕ピリミジン
291〜292（分解）
２ ３，６―ジアリル―２―ヒドロキシ
―３，４，６，７―テトラヒドロ―
４，５，７―トリオキソ―5H―ピ
ロロ〔３，４―ｄ〕ピリミジン
193〜194
３ ３，６―ジベンジル―２―ヒドロキ
シ―３，４，６，７―テトラヒドロ
―４，５，７―トリオキソ―5H―
ピロロ〔３，４―ｄ〕ピリミジン
224〜225
４ ３，６―ジフエニル―２―ヒドロキ
シ―３，４，６，７―テトラヒドロ
―４，５，７―トリオキソ―5H―
ピロロ〔３，４―ｄ〕ピリミジン
276（分解）（１エタノール付加物）
５ ３，６―ジ（ｐ―トリル）―２―ヒ
ドロキシ―３，４，６，７―テトラ
ヒドロ―４，５，７―トリオキソ―
5H―ピロロ〔３，４―ｄ〕ピリミ
ジン 276〜277（分解）
６ ３，６―ビス（２，４―ジクロロフ
エニル）―２―ヒドロキシ―３，
４，６，７―テトラヒドロ―４，
５，７―トリオキソ―5H―ピロロ
〔３，４―ｄ〕ピリミジン
262〜264（分解）
７ ６―（ｐ―クロロフエニル）―２―
ヒドロキシ―３，４，６，７―テト
ラヒドロ―３―（ｐ―トリル）―
４，５，７―トリオキソ―5H―ピ
ロロ〔３，４―ｄ〕ピリミジン
234（分解）（１エタノール付加物）
８ ３―ベンジル―２―ヒドロキシ―
３，４，６，７―テトラヒドロ―６
―（ｐ―トリル）―４，５，７―ト
リオキソ―5H―ピロロ〔３，４―
ｄ〕ピリミジン
270〜271（１エタノール付加物）
９ ３―（ｐ―クロロフエニル）―２―
ヒドロキシ―６―フエニル―４，
５，６，７―テトラヒドロ―４，
５，７―トリオキソ―5H―ピロロ
〔３，４―ｄ〕ピリミジン
295（分解）
10 ３，６―ジシクロヘキシル―２―ヒ
ドロキシ―３，４，６，７―テトラ
ヒドロ―４，５，７―トリオキソ―
5H―ピロロ〔３，４―ｄ〕ピリミ
ジン
290（分解）（1/2ジオキサン付加物）
この発明のピロロピリミジン誘導体は、たとえ
ば下記(1)および(2)の方法で合成することができ
る。
(1) 式
（式中、R1およびR2は、それぞれ前記と同じ
意味を有する。）で表わされるアミノマレイミ
ドと、ホスゲンまたはクロロギ酸トリメチルエ
ステルとを、ピリジンの存在下に反応させる方
法。
この反応は、式〔〕で表わされるアミノマ
レイミドを、ホスゲン１モル当り0.4〜１モル、
クロロギ酸トリメチルエステル１モル当り0.2
〜0.5モルと、ピリジンを、ホスゲン１モル当
り約２モル、クロロギ酸トリメチルエステル１
モル当り約４モル使用し、ベンゼン、トルエ
ン、クロロベンゼン、ジクロロベンゼンなどの
芳香族炭化水素、塩化メチレン、クロロホル
ム、四塩化炭素、塩化エチレンなどのハロゲン
化炭化水素などの溶媒の存在下に、通常−20〜
100℃の範囲の温度で、１〜30時間行なわれる。
式〔〕で表わされるアミノマレイミドは、
式 Ｎ≡Ｃ−COOR4 〔〕
（式中、R4は炭素数１〜４のアルキル基を示
す。）で表わされるシアノギ酸エステルと、
式
（式中、R1とR2は、それぞれ前記と同じ意味
を有する。）で表わされるマロンアミドとを、
塩化亜鉛と第三アミンの存在下で反応させ、つ
いで得られる反応生成物を酸性水溶液で処理す
る方法で合成することができる。
(2) 式
（式中、R1とR2は、それぞれ前記と同じ意味
を有する。）で表わされる３―（カルバモイル）
アミノ―４―エトキシカルボニルマレイミド
を、三フツ化ホウ素の存在下で50〜150℃の範
囲の温度で加熱して、閉環する方法。
この反応は、反応溶媒の不存在下、または反
応溶媒、たとえばベンゼン、トルエン、クロロ
ベンゼン、ジクロロベンゼンなどの芳香族炭化
水素、塩化エチレンなどのハロゲン化炭化水素
の存在下に、通常１〜30時間行なわれる。
式〔〕で表わされるカルバモイルアミノマ
レイミドは、
式
（式中、R1は前記と同一の意味を有する。）で
表わされるアミノマレイミドと、ホスゲンまた
はクロロギ酸トリクロロメチルエステルとを、
ピリジンの存在下に反応させ、ついで反応生成
物を
式 R2−NH2 〔〕
（式中、R2は前記と同一の意味を有する。）で
表わされるアミンと反応させる方法で合成する
ことができる。
式〔〕で表わされるアミノマレイミドは、
式
（式中、R5とR6は、それぞれ炭素数１〜４の
アルキル基を示す。）で表わされるアルコキシ
イミノ酢酸エステルと、
式
（式中、R1は前記と同一の意味を有する。）で
表わされるエトキシカルボニル酢酸アミドとを
反応させる方法（本特許出願人の出願に係る特
願昭55―140405号明細書参照）で合成すること
ができる。
以下に、この発明ピロロピリミジン誘導体の合
成例を示す。
合成例 １
（化合物番号１）
(1) 減圧下、110℃で15分間乾燥した塩化亜鉛
14.31ｇに塩化メチレン150mlを加えて得た懸濁
液を撹拌しながら、これにＮ，N′―ジメチル
マロンアミド6.51ｇを室温で加え、ついでトリ
エチルアミン10.12ｇを含む塩化メチレン50ml
を滴下した。混合物を室温で１時間撹拌した
後、混合物に室温でシアノギ酸エチル9.91ｇを
含む塩化メチレン50mlを滴下した。混合物を加
熱し、還流下にシアノギ酸エチルとＮ，N′―
ジメチルマロンアミドを15時間反応させた。
反応後、得られた反応生成物を氷水で冷却し
ながら、これに１規定塩酸100mlを加えた。氷
水冷却下に0.5時間の撹拌によつて得られた反
応混合物を過して、３―アミノ―１―メチル
―４―（メチルカルバモイル）マレイミド結晶
3.17ｇを得た。これをメタノールで再結晶し
て、つぎの反応に供した。
(2) (1)の反応で得た３―アミノ―１―メチル―４
―（メチルカルバモイル）マレイミド0.92ｇと
ピリジン1.71ｇを含む塩化エチレン20mlに、寒
剤（氷―食塩）冷却下、クロロギ酸トリクロロ
メチルエステル1.07ｇを含む塩化エチレン20ml
を滴下した後、混合物を室温で撹拌しながら、
１日間反応させた。
反応後、得られた反応生成混合物に水50mlを
加えて過し、３，６―ジメチル―２―ヒドロ
キシ―３，４，６，７―テトラヒドロ―４，
５，７―トリオキソ―5H―ピロロ〔３，４―
ｄ〕ピリミジンの結晶0.49ｇを得た。これをエ
タノールで再結晶して、分解点291〜292℃の橙
色針状結晶を得た。その元素分析値をつぎに示
す。
Ｃ Ｈ Ｎ
分析値 45.98 3.40 19.87
計算値 45.94 3.38 20.09
（C8H7N3O4として）
合成例 ２
（化合物番号８）
(1) エトキシイミノ酢酸エチル1.45ｇとエトキシ
カルボニル酢酸（ｐ―トルイド）2.21ｇを含む
エタノール５mlを、加熱して、還流下に20時間
反応させた。
反応後、混合物を室温まで冷却した後、過
して、３―アミノ―４―エトキシカルボニルマ
レイミドの結晶1.51ｇを得た。これをエタノー
ル45mlで再結晶して、融点188〜190℃の黄色微
針状結晶0.8ｇを得た。
(2) (1)の方法に準じて合成した３―アミノ―４―
エトキシカルボニルマレイミド2.77ｇとピリジ
ン２ｇを含む塩化エチレン40mlに、寒剤（氷―
食塩）冷却下、クロロギ酸トリメチルエステル
1.25ｇを含む塩化エチレン30mlを滴下した後、
混合物を室温で撹拌しながら、４時間反応させ
た。
反応後、得られた反応生成混合物に、寒剤
（氷―食塩）冷却下、ベンジルアミン1.35ｇを
含む塩化エチレン20mlを滴下した後、混合物を
加熱して、還流下に１時間反応させた。
得られた反応生成混合物に、水50mlを加え、
水層と有機層とに分液した。有機層を無水硫酸
ナトリウムで乾燥した後、減圧下に濃縮して得
た残渣に、ベンゼン10mlを加え、過して、３
―（ベンジルカルバモイル）アミノ―４―エト
キシカルボニル―１―（ｐ―トリル）マレイミ
ドの結晶2.23ｇを得た。これをエタノールで再
結晶して、融点178〜179℃の黄色柱状結晶を得
た。
(3) (2)の反応で得た３―（ベンジルカルバモイ
ル）アミノ―４―エトキシカルボニル―１―
（ｐトリル）マレイミド１ｇと三フツ化ホウ
素・エーテラート0.35ｇを含む塩化エチレン６
mlを加熱して、還流下に20時間反応させた。
反応後、得られた反応生成混合物に、室温で
水10mlを加えて過し、３―ベンジル―２―ヒ
ドロキシ―３，４，６，７―テトラヒドロ―６
―（ｐ―トリル）―４，５，７―トリオキソ―
5H―ピロロ〔３，４―ｄ〕ピリミジンの結晶
0.15ｇを得た。これをエタノールで再結晶し
て、エタノールとのモル比１：１の付加物とし
て、融点270〜271℃の黄色結晶を得た。その元
素分析値をつぎに示す。
Ｃ Ｈ Ｎ
分析値 64.79 4.95 10.50
計算値 64.86 5.20 10.31
（C22H21N3O5として）[Formula] (R 3 represents an alkyl group having 1 to 4 carbon atoms or a halogen atom, and n is 0, 1, 2 or 3). ] 2-hydroxy-3,4,6,7-tetrahydro-4,5,7-
It is a trioxo-5H-pyrrolo[3,4-d]pyrimidine derivative. The pyrrolopyrimidine derivative of this invention can be used for agricultural chemicals,
It is useful as a medicine and also as an intermediate thereof. It is particularly useful as an agricultural and horticultural fungicide against rice leaf blight. The physical properties of specific examples of pyrrolopyrimidine derivatives are shown below. Compound number Compound name Melting point (℃) 1 3,6-dimethyl-2-hydroxy-3,4,6,7-tetrahydro-
4,5,7-trioxo-5H-pyrrolo[3,4-d]pyrimidine
291-292 (decomposition) 2 3,6-diallyl-2-hydroxy-3,4,6,7-tetrahydro-
4,5,7-trioxo-5H-pyrrolo[3,4-d]pyrimidine
193-194 3 3,6-dibenzyl-2-hydroxy-3,4,6,7-tetrahydro-4,5,7-trioxo-5H-
pyrrolo[3,4-d]pyrimidine
224-225 4 3,6-diphenyl-2-hydroxy-3,4,6,7-tetrahydro-4,5,7-trioxo-5H-
pyrrolo[3,4-d]pyrimidine
276 (Decomposition) (1 ethanol adduct) 5 3,6-di(p-tolyl)-2-hydroxy-3,4,6,7-tetrahydro-4,5,7-trioxo-
5H-pyrrolo[3,4-d]pyrimidine 276-277 (decomposition) 6 3,6-bis(2,4-dichlorophenyl)-2-hydroxy-3,
4,6,7-tetrahydro-4,
5,7-trioxo-5H-pyrrolo[3,4-d]pyrimidine
262-264 (decomposition) 7 6-(p-chlorophenyl)-2-
Hydroxy-3,4,6,7-tetrahydro-3-(p-tolyl)-
4,5,7-trioxo-5H-pyrrolo[3,4-d]pyrimidine
234 (decomposition) (1 ethanol adduct) 8 3-benzyl-2-hydroxy-
3,4,6,7-tetrahydro-6
-(p-tolyl)-4,5,7-trioxo-5H-pyrrolo[3,4-
d] Pyrimidine
270-271 (1 ethanol adduct) 9 3-(p-chlorophenyl)-2-
hydroxy-6-phenyl-4,
5,6,7-tetrahydro-4,
5,7-trioxo-5H-pyrrolo[3,4-d]pyrimidine
295 (Decomposition) 10 3,6-dicyclohexyl-2-hydroxy-3,4,6,7-tetrahydro-4,5,7-trioxo-
5H-pyrrolo[3,4-d]pyrimidine
290 (Decomposition) (1/2 dioxane adduct) The pyrrolopyrimidine derivative of this invention can be synthesized, for example, by the following methods (1) and (2). (1 set A method of reacting aminomaleimide represented by the formula (wherein R 1 and R 2 each have the same meanings as above) with phosgene or chloroformic acid trimethyl ester in the presence of pyridine. In this reaction, 0.4 to 1 mol of aminomaleimide represented by the formula [] per 1 mol of phosgene,
0.2 per mole of chloroformic acid trimethyl ester
~0.5 moles of pyridine, approximately 2 moles per mole of phosgene, and 1 mole of chloroformate trimethyl ester.
About 4 moles per mole is used, usually in the presence of a solvent such as aromatic hydrocarbons such as benzene, toluene, chlorobenzene, dichlorobenzene, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, ethylene chloride, etc. 20〜
It is carried out at temperatures ranging from 100°C for 1 to 30 hours. Aminomaleimide represented by the formula [] is a cyanoformate ester represented by the formula N≡C-COOR 4 [] (in the formula, R 4 represents an alkyl group having 1 to 4 carbon atoms), and the formula (In the formula, R 1 and R 2 each have the same meaning as above.)
It can be synthesized by reacting zinc chloride in the presence of a tertiary amine and then treating the resulting reaction product with an acidic aqueous solution. (2) Equation 3-(carbamoyl) represented by (wherein R 1 and R 2 each have the same meaning as above)
A method of ring-closing amino-4-ethoxycarbonylmaleimide by heating it at a temperature in the range of 50 to 150°C in the presence of boron trifluoride. This reaction is usually carried out for 1 to 30 hours in the absence of a reaction solvent or in the presence of a reaction solvent, such as an aromatic hydrocarbon such as benzene, toluene, chlorobenzene, or dichlorobenzene, or a halogenated hydrocarbon such as ethylene chloride. It will be done. Carbamoylaminomaleimide represented by the formula [] is the formula (wherein R 1 has the same meaning as above) and phosgene or chloroformic acid trichloromethyl ester,
It can be synthesized by a method of reacting in the presence of pyridine and then reacting the reaction product with an amine represented by the formula R 2 -NH 2 [] (wherein R 2 has the same meaning as above). can. Aminomaleimide represented by the formula [] is the formula (In the formula, R 5 and R 6 each represent an alkyl group having 1 to 4 carbon atoms.) An alkoxyiminoacetic acid ester represented by the formula (In the formula, R 1 has the same meaning as above.) Synthesized by a method of reacting with ethoxycarbonylacetic acid amide represented by can do. An example of synthesis of the pyrrolopyrimidine derivative of the present invention is shown below. Synthesis Example 1 (Compound No. 1) (1) Zinc chloride dried at 110°C for 15 minutes under reduced pressure
150 ml of methylene chloride was added to 14.31 g, and 6.51 g of N,N'-dimethylmalonamide was added thereto at room temperature while stirring, followed by 50 ml of methylene chloride containing 10.12 g of triethylamine.
was dripped. After the mixture was stirred at room temperature for 1 hour, 50 ml of methylene chloride containing 9.91 g of ethyl cyanoformate was added dropwise to the mixture at room temperature. The mixture is heated and ethyl cyanoformate and N,N′- are heated under reflux.
Dimethylmalonamide was allowed to react for 15 hours. After the reaction, 100 ml of 1N hydrochloric acid was added to the obtained reaction product while cooling it with ice water. The reaction mixture obtained by stirring for 0.5 hours under cooling with ice water was filtered to obtain 3-amino-1-methyl-4-(methylcarbamoyl)maleimide crystals.
3.17g was obtained. This was recrystallized from methanol and used for the next reaction. (2) 3-amino-1-methyl-4 obtained by the reaction of (1)
- Add 20 ml of ethylene chloride containing 0.92 g of (methylcarbamoyl)maleimide and 1.71 g of pyridine to 20 ml of ethylene chloride containing 1.07 g of trichloromethyl chloroformate under cooling with a cryogen (ice-salt).
After adding dropwise, while stirring the mixture at room temperature,
The reaction was allowed to proceed for 1 day. After the reaction, 50 ml of water was added to the resulting reaction product mixture and filtered to give 3,6-dimethyl-2-hydroxy-3,4,6,7-tetrahydro-4,
5,7-trioxo-5H-pyrrolo [3,4-
d] 0.49 g of pyrimidine crystals were obtained. This was recrystallized with ethanol to obtain orange needle-like crystals with a decomposition point of 291-292°C. The elemental analysis values are shown below. C H N Analytical value 45.98 3.40 19.87 Calculated value 45.94 3.38 20.09 (as C 8 H 7 N 3 O 4 ) Synthesis example 2 (Compound No. 8) (1) Ethyl ethoxyiminoacetate 1.45g and ethoxycarbonylacetic acid (p-toluide) 5 ml of ethanol containing 2.21 g was heated and reacted under reflux for 20 hours. After the reaction, the mixture was cooled to room temperature and filtered to obtain 1.51 g of crystals of 3-amino-4-ethoxycarbonylmaleimide. This was recrystallized from 45 ml of ethanol to obtain 0.8 g of yellow fine needle crystals with a melting point of 188-190°C. (2) 3-Amino-4- synthesized according to the method in (1)
40 ml of ethylene chloride containing 2.77 g of ethoxycarbonyl maleimide and 2 g of pyridine is
Salt) Under cooling, chloroformic acid trimethyl ester
After dropping 30ml of ethylene chloride containing 1.25g,
The mixture was allowed to react for 4 hours with stirring at room temperature. After the reaction, 20 ml of ethylene chloride containing 1.35 g of benzylamine was added dropwise to the resulting reaction product mixture while cooling with a cryogen (ice-salt), and the mixture was heated and reacted under reflux for 1 hour. Add 50 ml of water to the resulting reaction product mixture,
The mixture was separated into an aqueous layer and an organic layer. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. 10 ml of benzene was added to the obtained residue, filtered, and
2.23 g of crystals of -(benzylcarbamoyl)amino-4-ethoxycarbonyl-1-(p-tolyl)maleimide were obtained. This was recrystallized from ethanol to obtain yellow columnar crystals with a melting point of 178-179°C. (3) 3-(benzylcarbamoyl)amino-4-ethoxycarbonyl-1- obtained in the reaction of (2)
Ethylene chloride 6 containing 1 g of (ptolyl)maleimide and 0.35 g of boron trifluoride etherate
ml was heated and reacted under reflux for 20 hours. After the reaction, 10 ml of water was added to the resulting reaction product mixture at room temperature and filtered to give 3-benzyl-2-hydroxy-3,4,6,7-tetrahydro-6.
-(p-tolyl)-4,5,7-trioxo-
5H-pyrrolo[3,4-d]pyrimidine crystal
0.15g was obtained. This was recrystallized with ethanol to obtain yellow crystals with a melting point of 270-271°C as an adduct with ethanol in a molar ratio of 1:1. The elemental analysis values are shown below. C H N Analysis value 64.79 4.95 10.50 Calculated value 64.86 5.20 10.31 (as C 22 H 21 N 3 O 5 )
Claims (1)
４のアルキル基、炭素数２〜４のアルケニル基、
炭素数５〜７のシクロアルキル基、炭素数７〜10
のアラルキル基、または【式】（R3は 炭素数１〜４のアルキル基またはハロゲン原子を
示し、ｎは０，１，２または３である。）で表わ
される基を示す。〕で表わされるピロロピリミジ
ン誘導体。[Claims] 1 formula [In the formula, R 1 and R 2 each have a carbon number of 1 to
4 alkyl group, alkenyl group having 2 to 4 carbon atoms,
Cycloalkyl group having 5 to 7 carbon atoms, 7 to 10 carbon atoms
or a group represented by the formula (R 3 represents an alkyl group having 1 to 4 carbon atoms or a halogen atom, and n is 0, 1, 2 or 3). ] A pyrrolopyrimidine derivative represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15949681A JPS5862174A (en) | 1981-10-08 | 1981-10-08 | Pyrrolopyrimidine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15949681A JPS5862174A (en) | 1981-10-08 | 1981-10-08 | Pyrrolopyrimidine derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5862174A JPS5862174A (en) | 1983-04-13 |
| JPH0216310B2 true JPH0216310B2 (en) | 1990-04-16 |
Family
ID=15695034
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15949681A Granted JPS5862174A (en) | 1981-10-08 | 1981-10-08 | Pyrrolopyrimidine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5862174A (en) |
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|---|---|---|---|---|
| WO2018031990A1 (en) * | 2016-08-12 | 2018-02-15 | Nanjing Gator Meditech Company, Ltd. | Protein kinase regulators |
-
1981
- 1981-10-08 JP JP15949681A patent/JPS5862174A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5862174A (en) | 1983-04-13 |
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