JPH0216309B2 - - Google Patents
Info
- Publication number
- JPH0216309B2 JPH0216309B2 JP15807481A JP15807481A JPH0216309B2 JP H0216309 B2 JPH0216309 B2 JP H0216309B2 JP 15807481 A JP15807481 A JP 15807481A JP 15807481 A JP15807481 A JP 15807481A JP H0216309 B2 JPH0216309 B2 JP H0216309B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- hydroxy
- ethylene chloride
- trioxo
- pyrrolo
- 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
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 claims description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
- TUZVMPXGFZSNBG-UHFFFAOYSA-N 3-aminopyrrole-2,5-dione Chemical compound NC1=CC(=O)NC1=O TUZVMPXGFZSNBG-UHFFFAOYSA-N 0.000 claims description 11
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 150000004944 pyrrolopyrimidines Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl 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
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 22
- 239000000203 mixture Substances 0.000 description 20
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 15
- 239000013078 crystal Substances 0.000 description 14
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000001816 cooling 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000007795 chemical reaction product Substances 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 238000000921 elemental analysis Methods 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 239000012046 mixed solvent Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- SAHJOSKPGKTZTC-UHFFFAOYSA-N 5h-pyrrolo[3,4-d]pyrimidine Chemical compound C1=NC=C2CN=CC2=N1 SAHJOSKPGKTZTC-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000725 suspension Substances 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
ン類の製造法である。さらに詳しくは、この発明
は、
式
〔式中、R1は炭素数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 is a method for producing pyrrolopyrimidines, which are new compounds. More specifically, the invention provides the formula [In the formula, R 1 is an alkyl group having 1 to 4 carbon atoms, an alkenyl group having 2 to 4 carbon atoms, a cycloalkyl group having 5 to 7 carbon atoms, an aralkyl group having 7 to 10 carbon atoms, or
【式】（R2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
わされるアミノマレイミド類と、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ることを特徴とする
式
（式中、R1は前記と同一の意味を有する。）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〕ピリミジン類の製造法である。
式〔〕で表わされるピロロピリミジン類は、
新規化合物であり、医薬、農薬、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。
式〔〕で表わされるアミノマレイミド類の具
体例としては、３―アミノ―１―メチル―４―
（メチルカルバモイル）マレイミド、３―アミノ
―１―エチル―４―（エチルカルバモイル）マレ
イミド、３―アミノ―１―プロピル―４―（プロ
ピルカルバモイル）マレイミド、３―アミノ―１
―ブチル―４―（ブチルカルバモイル）マレイミ
ド、１―アリル―３―（アリルカルバモイル）―
４―アミノマレイミド、３―アミノ―１―シクロ
ヘキシル―４―（シクロヘキシルカルバモイル）
マレイミド、３―アミノ―１―ベンジル―４―
（ベンジルカルバモイル）マレイミド、３―アミ
ノ―１―フエニル―４―（フエニルカルバモイ
ル）マレイミド、３―アミノ―１―クロロフエニ
ル―４―（クロロフエニルカルバモイル）マレイ
ミド、３―アミノ―１―ジクロロフエニル―４―
（ジクロロフエニルカルバモイル）マレイミドな
どが挙げられる。
この発明の方法におけるピリジン存在下での式
〔〕で表わされるアミノマレイミド類とホスゲ
ンまたはクロロギ酸トリクロロメチルエステルと
の反応は、溶媒を用いて行なうことが好ましい。
溶媒としては、この発明の方法における反応に不
活性なものであれば、どのようなものでもよく、
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が挙げられ
る。
なお、溶媒は反応に先立ち十分に脱水しておく
ことが好ましい。
原料の添加順序については特に制限はないが、
アミノマレイミドおよびピリジンを含む有機溶媒
の溶液または懸濁液に、ホスゲンまたはクロロギ
酸トリクロロメチルエステルの有機溶媒溶液を添
加するのが便利である。
アミノマレイミド類の使用量は、ホスゲン１モ
ル当り0.4〜１モル、クロロギ酸トリクロロメチ
ルエステル１モル当り0.2〜0.5モルであることが
好ましく、目的物を収率よく得るためにはホスゲ
ン１モル当り0.4〜0.5モル、クロロギ酸トリクロ
ロメチルエステル１モル当り0.2〜0.25モルであ
ることが特に好ましい。
ピリジンの使用量は、ホスゲン１モル当り約２
モル、クロロギ酸トリクロロメチルエステル１モ
ル当り約４モルであることが好ましい。
反応温度は、過度に高いと目的生成物の収率が
低下するので、一般には−20〜100℃の範囲の温
度を採用するのが好ましい。反応時間は通常１〜
30時間である。
目的生成物であるピロロピリミジン類は、たと
えば、つぎの方法によつて単離することができ
る。
反応生成混合物を水洗して、副生する塩化ピリ
ジニウムを水溶液として除去した後、有機溶媒を
留去し、目的生成物を含む混合物を取得し、この
後、再結晶法などの慣用の精製法によつて目的生
成物の精製品を単離する。
この発明で得られる式〔〕で表わされるピロ
ロピリミジン類の具体例としては、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、３，６―ジエチル―
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、３，６―ジプロピル―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、３，６―ジブチル―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、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、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、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、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、
３，６―ビス（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、３，６―ビス（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〕ピリミジンなどが挙げられる。
つぎに実施例を示す。実施例において、ピロロ
ピリミジンの収率は、使用したアミノマレイミド
基準の収率である。
実施例 １
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を滴下して加えた後、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（47％：収率、以下同じ）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）
実施例 ２
１―アリル―３―（アリルカルバモイル）―４
―アミノマレイミド1.18ｇとピリジン1.7ｇを含
む塩化エチレ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、混合物を寒剤
（氷―食塩）冷却下に撹拌しながら、５時間反応
させた。
反応後、得られた反応生成混合物、寒剤（氷―
食塩）冷却下、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を、シリカゲル
（ワコーゲルＣ―200，200ｇ）を詰めたカラム
（直径30mm）に通し、塩化エチレンとエタノール
との容量比９：１の混合溶媒で溶離した。溶媒
320mlで溶出して得た溶液を、減圧下に濃縮した。
残渣にベンゼン20mlを加えて過し、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〕ピリミジンの結晶0.86ｇ（66
％）を得た。これをベンゼンで再結晶して、融点
193〜194℃の微黄色微針状結晶を得た。その元素
分析値をつぎに示す。
Ｃ Ｈ Ｎ
分析値 55.05 4.20 16.32
計算値 55.17 4.25 16.08
（C12H11N3O4として）
実施例 ３
３―アミノ―１―ベンジル―４―（ベンジルカ
ルバモイル）マレイミド1.68ｇとピリジン1.68ｇ
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1.02
ｇ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、20時間反応させた。
反応後、得られた反応生成混合物に、水50mlを
加え、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
得た残渣を、シリカゲル（ワコーゲルＣ―200，
200ｇ）を詰めたカラム（直径30mm）に通し、塩
化エチレンと酢酸エチルとの容量比７：３の混合
溶媒で溶離した。まず溶媒240mlで溶出した後、
溶媒200mlで溶出して得た溶液を減圧下に濃縮し
た。残渣にベンゼン20mlを加えて過し、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〕ピリミジンの結晶1.59ｇ
（88％）を得た。これを酢酸エチルで再結晶して、
融点224〜225℃の淡黄色結晶を得た。その元素分
析値をつぎに示す。
Ｃ Ｈ Ｎ
分析値 66.67 4.16 11.72
計算値 66.48 4.18 11.63
（C20H15N3O4として）
実施例 ４
３―アミノ―１―フエニル―４―（フエニルカ
ルバモイル）マレイミド3.07ｇとピリジン1.94ｇ
を含む塩化エチレン40mlに、寒剤（氷―食塩）冷
却下、ホスゲン1.21ｇ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30分間
反応させた。
反応後、得られた反応生成混合物に、室温で水
25mlを加えて過し、原料アミノマレイミドの結
晶0.55ｇを回収した。液を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、減圧下に濃縮した。残渣をエタノール50mlで
再結晶して、分解点276℃の黄色微針状結晶とし
て、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〕ピリミジンと
エタノールとのモル比１：１の付加物0.59ｇ（16
％）を得た。その元素分析値をつぎに示す。
Ｃ Ｈ Ｎ
分析値 63.35 4.36 11.30
計算値 63.32 4.52 11.08
（C20H17N3O5として）
実施例 ５
３―アミノ―１―フエニル―４―（フエニルカ
ルバモイル）マレイミド1.54ｇとピリジン1.68ｇ
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1.12
ｇ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、16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
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
縮して得た残渣にエタノール50mlを加えて過
し、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〕ピリミジンの
結晶1.41ｇ（84％）を得た。
実施例 ６
３―アミノ―１―（Ｐ―トリル）―４―（Ｐ―
トリルカルバモイル）マレイミド3.35ｇとピリジ
ン1.94ｇを含む塩化エチレン40mlに、寒剤（氷―
食塩）冷却下、ホスゲン1.21ｇ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日反応させた。
反応後、得られた反応生成混合物に、室温で水
25mlを加え、過して、原料アミノマレイミドの
結晶0.93ｇを回収した。液を水層と有機層とに
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25
mlを加えて過し、ついで集物を塩化エチレン
30mlで洗つて、さらに原料アミノマレイミドの結
晶0.65ｇを回収した。液と洗浄液を一緒にし
て、減圧下に濃縮した。残渣を、シリカゲル（ワ
コーゲルＣ―200，70ｇ）を詰めたカラム（直径
25mm）に通し、ベンゼンと酢酸エチルとの混合溶
媒で溶離した。まず容量比９：１の混合溶媒500
ml、ついで容量比４：１の混合溶媒150mlで溶出
した後、容量比４：１の混合溶媒300mlで溶出し
て得た溶液を減圧下に濃縮して、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〕ピリミジンの結晶0.34ｇ
（９％）を得た。これをエタノールで再結晶して、
分解点276〜77℃の黄色微針状結晶を得た。
その元素分析値をつぎに示す。
Ｃ Ｈ Ｎ
分析値 66.25 4.19 11.79
計算値 66.48 4.18 11.63
（C20H15N3O4として）
実施例 ７
３―アミノ―１―（２，４―ジクロロフエニ
ル）―４―（２，４―ジクロロフエニルカルバモ
イル）マレイミド2.23ｇとピリジン1.7ｇ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1.06ｇを含
む塩化エチレン20mlを滴下した後、混合物を寒剤
（氷―食塩）冷却下で撹拌しながら、20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、減圧下に濃縮した。残渣を塩化エチレン
30mlで再結晶して、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〕ピリミジンの淡黄色
針状結晶0.7ｇ（30％、分解点262〜264℃）を得
た。その元素分析値をつぎに示す。
Ｃ Ｈ Ｎ Cl
分析値 45.93 1.78 8.67 29.99
計算値 45.89 1.50 8.92 30.10
（C18H7Cl4N3O4として）
実施例 ８
３―アミノ―１―シクロヘキシル―４―（シク
ロヘキシルカルバモイル）マレイミド2.72ｇとピ
リジン3.37ｇを含む塩化エチレン70ml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2.27ｇ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日反応
させた。
反応後、得られた反応生成混合物に、室温で水
50mlを加えて過し、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〕ピリミジンの結晶1.35ｇ（46％）を得
た。液を水層と有機層とに分液し、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
た。残渣をジオキサンで再結晶して、さらに目的
物のピロピリミジンを、ジオキサンと付加物（モ
ル比２：１）として得た。収量0.51ｇ（15％）。
分解点90℃。その元素分析値をつぎに示す。
Ｃ Ｈ Ｎ
分析値 61.84 7.22 11.19
計算値 61.68 6.99 10.79
（C18H23N3O4・1/2C4H8O2として）[Formula] (R 2 represents an alkyl group having 1 to 4 carbon atoms or a halogen atom, n is 0, 1, 2
Or 3. ) represents a group. ] is characterized by reacting an aminomaleimide represented by the formula with phosgene or chloroformic acid trichloromethyl ester in the presence of pyridine. 2- hydroxy -3,4,6,7-tetrahydro-4,5,7-trioxo-5H-pyrrolo[3,4-d ] This is a method for producing pyrimidines. Pyrrolopyrimidines represented by the formula [] are
It is a new compound and is useful as a medicine, agrochemical, and an intermediate thereof. It is particularly useful as an agricultural and horticultural fungicide against rice leaf blight. Specific examples of aminomaleimides represented by the formula [] include 3-amino-1-methyl-4-
(Methylcarbamoyl)maleimide, 3-amino-1-ethyl-4-(ethylcarbamoyl)maleimide, 3-amino-1-propyl-4-(propylcarbamoyl)maleimide, 3-amino-1
-Butyl-4-(butylcarbamoyl)maleimide, 1-allyl-3-(allylcarbamoyl)-
4-Aminomaleimide, 3-amino-1-cyclohexyl-4-(cyclohexylcarbamoyl)
Maleimide, 3-amino-1-benzyl-4-
(benzylcarbamoyl)maleimide, 3-amino-1-phenyl-4-(phenylcarbamoyl)maleimide, 3-amino-1-chlorophenyl-4-(chlorophenylcarbamoyl)maleimide, 3-amino-1-dichlorophenyl- 4-
(dichlorophenylcarbamoyl)maleimide and the like. In the method of this invention, the reaction of the aminomaleimide represented by the formula [] with phosgene or trichloromethyl chloroformate in the presence of pyridine is preferably carried out using a solvent.
Any solvent may be used as long as it is inert to the reaction in the method of this invention.
Examples include aromatic hydrocarbons such as benzene, toluene, chlorobenzene, and dichlorobenzene, and halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, and ethylene chloride. Note that the solvent is preferably sufficiently dehydrated prior to the reaction. There are no particular restrictions on the order of addition of raw materials, but
It is convenient to add a solution of phosgene or chloroformic acid trichloromethyl ester in an organic solvent to a solution or suspension containing the aminomaleimide and pyridine in an organic solvent. The amount of aminomaleimides to be used is preferably 0.4 to 1 mol per mol of phosgene and 0.2 to 0.5 mol per mol of chloroformic acid trichloromethyl ester, and in order to obtain the target product with a good yield, it is 0.4 to 1 mol per mol of phosgene. ~0.5 mol, particularly preferably 0.2 to 0.25 mol per mole of chloroformic acid trichloromethyl ester. The amount of pyridine used is approximately 2 per mole of phosgene.
mole, preferably about 4 moles per mole of chloroformic acid trichloromethyl ester. If the reaction temperature is too high, the yield of the desired product will decrease, so it is generally preferable to employ a temperature in the range of -20 to 100°C. Reaction time is usually 1~
It is 30 hours. The desired product, pyrrolopyrimidine, can be isolated, for example, by the following method. After washing the reaction product mixture with water to remove by-product pyridinium chloride as an aqueous solution, the organic solvent is distilled off to obtain a mixture containing the desired product, which is then subjected to a conventional purification method such as recrystallization. Thus, the purified product of interest is isolated. Specific examples of pyrrolopyrimidines represented by the formula [] obtained in this invention include 3,6-dimethyl-2-hydroxy-3,4,6,7-tetrahydro-4,5,7-trioxo-5H- Pyrrolo[3,4-d]pyrimidine, 3,6-diethyl-
2-Hydroxy-3,4,6,7-tetrahydro-4,5,7-trioxo-5H-pyrrolo[3,
4-d]pyrimidine, 3,6-dipropyl-2-
Hydroxy-3,4,6,7-tetrahydro-
4,5,7-trioxo-5H-pyrrolo[3,4
-d] Pyrimidine, 3,6-dibutyl-2-hydroxy-3,4,6,7-tetrahydro-4,
5,7-trioxo-5H-pyrrolo [3,4-d]
Pyrimidine, 3,6-diallyl-2-hydroxy-3,4,6,7-tetrahydro-4,5,7-
Trioxo-5H-pyrrolo[3,4-d]pyrimidine, 3,6-dicyclohexyl-2-hydroxy-3,4,6,7-tetrahydro-4,5,7
-trioxo-5H-pyrrolo[3,4-d]pyrimidine, 3,6-dibenzyl-2-hydroxy-
3,4,6,7-tetrahydro-4,5,7-trioxo-5H-pyrrolo[3,4-d]pyrimidine, 3,6-diphenyl-2-hydroxy-3,
4,6,7-tetrahydro-4,5,7-trioxo-5H-pyrrolo[3,4-d]pyrimidine,
3,6-bis(chlorophenyl)-2-hydroxy-3,4,6,7-tetrahydro-4,5,7
-trioxo-5H-pyrrolo[3,4-d]pyrimidine, 3,6-bis(dichlorophenyl)-2
-Hydroxy-3,4,6,7-tetrahydro-
4,5,7-trioxo-5H-pyrrolo[3,4
-d] Pyrimidine, etc. Next, examples will be shown. In the Examples, the yield of pyrrolopyrimidine is the yield based on the aminomaleimide used. Example 1 To 20 ml of ethylene chloride containing 0.92 g of 3-amino-1-methyl-4-(methylcarbamoyl)maleimide and 1.71 g of pyridine, 1.07 g of trichloromethyl chloroformate was added under cooling with a cryogen (ice-salt).
After adding dropwise 20 ml of ethylene chloride containing 20 ml of ethylene chloride, the mixture was allowed to react for 1 day with stirring at room temperature. 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-
0.49 g (47% yield, same hereinafter) of crystals of trioxo-5H-pyrrolo[3,4-d]pyrimidine was obtained. This was recrystallized with ethanol and the decomposition point was 291.
Orange needle-shaped crystals were obtained at ~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 ) Example 2 1-allyl-3-(allylcarbamoyl)-4
- Add 20 ml of ethylene chloride containing 1.18 g of aminomaleimide and 1.7 g of pyridine under cooling with a cryogen (ice-salt).
After 20 ml of ethylene chloride containing 1.07 g of chloroformic acid trichloromethyl ester was added dropwise, the mixture was allowed to react for 5 hours while being stirred and cooled with a cryogen (ice-salt). After the reaction, the resulting reaction product mixture was mixed with a cryogen (ice-
Salt) While cooling, 50 ml of water was added to separate into an aqueous layer and an organic layer. After drying the organic layer over anhydrous sodium sulfate, the resulting residue was concentrated under reduced pressure and passed through a column (diameter 30 mm) packed with silica gel (Wako Gel C-200, 200 g) to determine the volume ratio of ethylene chloride and ethanol. Elution was performed with a 9:1 mixed solvent. solvent
The solution obtained by elution with 320 ml was concentrated under reduced pressure.
20 ml of benzene was added to the residue and filtered to obtain 3,6-diallyl-2-hydroxy-3,4,6,7-tetrahydro-4,5,7-trioxo-5H-pyrrolo[3,4-d]pyrimidine. Crystal 0.86g (66
%) was obtained. This was recrystallized from benzene to give a melting point of
Pale yellow fine needle crystals at 193-194°C were obtained. The elemental analysis values are shown below. C H N Analytical value 55.05 4.20 16.32 Calculated value 55.17 4.25 16.08 (as C 12 H 11 N 3 O 4 ) Example 3 1.68 g of 3-amino-1-benzyl-4-(benzylcarbamoyl)maleimide and 1.68 g of pyridine
To 20ml of ethylene chloride containing chloroformate trichloromethyl ester under cooling with a cryogen (ice-salt)
After dropping 20 ml of ethylene chloride containing g, the mixture was reacted for 20 hours with stirring at room temperature. After the reaction, 50 ml of water was added to the resulting reaction product mixture to separate it into an aqueous layer and an organic layer. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.
The mixture was passed through a column (diameter 30 mm) packed with 200 g) and eluted with a mixed solvent of ethylene chloride and ethyl acetate in a volume ratio of 7:3. First, after elution with 240 ml of solvent,
The solution obtained by elution with 200 ml of solvent was concentrated under reduced pressure. Add 20 ml of benzene to the residue and filter it.
-dibenzyl-2-hydroxy-3,4,6,7
-Tetrahydro-4,5,7-trioxo-5H
-Pyrrolo[3,4-d]pyrimidine crystals 1.59g
(88%). This was recrystallized from ethyl acetate,
Pale yellow crystals with a melting point of 224-225°C were obtained. The elemental analysis values are shown below. C H N Analytical value 66.67 4.16 11.72 Calculated value 66.48 4.18 11.63 (as C 20 H 15 N 3 O 4 ) Example 4 3.07 g of 3-amino-1-phenyl-4-(phenylcarbamoyl)maleimide and 1.94 g of pyridine
20 ml of ethylene chloride containing 1.21 g of phosgene was added dropwise to 40 ml of ethylene chloride containing 1.21 g of phosgene under cooling with a cryogen (ice-salt), and the mixture was heated and reacted under reflux for 30 minutes. After the reaction, the resulting reaction product mixture was added with water at room temperature.
25 ml was added and filtered to recover 0.55 g of raw aminomaleimide crystals. The liquid was separated into an aqueous layer and an organic layer. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was recrystallized with 50 ml of ethanol to give 3,6-diphenyl-2-hydroxy-3, 3,6-diphenyl-2-hydroxy-3,
0.59 g (16
%) was obtained. The elemental analysis values are shown below. C H N Analytical value 63.35 4.36 11.30 Calculated value 63.32 4.52 11.08 (as C 20 H 17 N 3 O 5 ) Example 5 1.54 g of 3-amino-1-phenyl-4-(phenylcarbamoyl)maleimide and 1.68 g of pyridine
To 20 ml of ethylene chloride containing chloroformate trichloromethyl ester under cooling with a cryogen (ice-salt)
After dropping 20 ml of ethylene chloride containing g, the mixture was reacted for 16 hours with stirring at room temperature. After the reaction, the resulting reaction product mixture was added with water at room temperature.
50 ml was added to separate into an aqueous layer and an organic layer. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. 50 ml of ethanol was added to the resulting residue, filtered, and 3,6-diphenyl-2-hydroxy-3,
1.41 g (84%) of crystals of 4,6,7-tetrahydro-4,5,7-trioxo-5H-pyrrolo[3,4-d]pyrimidine were obtained. Example 6 3-amino-1-(P-tolyl)-4-(P-
40 ml of ethylene chloride containing 3.35 g of maleimide (tolylcarbamoyl) and 1.94 g of pyridine,
After cooling, 20 ml of ethylene chloride containing 1.21 g of phosgene was added dropwise, and the mixture was allowed to react for one day while stirring at room temperature. After the reaction, the resulting reaction product mixture was added with water at room temperature.
25 ml was added and filtered to recover 0.93 g of raw aminomaleimide crystals. The liquid was separated into an aqueous layer and an organic layer. After drying the organic layer over anhydrous sodium sulfate, 25% of benzene was added to the residue obtained by concentrating the organic layer under reduced pressure.
ml of ethylene chloride and filtrate the mixture.
After washing with 30 ml, 0.65 g of raw material aminomaleimide crystals were recovered. The liquid and washings were combined and concentrated under reduced pressure. The residue was transferred to a column (diameter
25 mm) and eluted with a mixed solvent of benzene and ethyl acetate. First, 500 ml of mixed solvent with a volume ratio of 9:1
ml, then eluted with 150 ml of a mixed solvent with a volume ratio of 4:1, and then eluted with 300 ml of a mixed solvent with a volume ratio of 4:1. The obtained solution was concentrated under reduced pressure to obtain 3,6-di(P
-tolyl)-2-hydroxy-3,4,6,7-
Tetrahydro-4,5,7-trioxo-5H-
Pyrrolo[3,4-d]pyrimidine crystals 0.34g
(9%) was obtained. This was recrystallized with ethanol,
Yellow microneedle crystals with a decomposition point of 276-77°C were obtained. The elemental analysis values are shown below. C H N Analytical value 66.25 4.19 11.79 Calculated value 66.48 4.18 11.63 (as C 20 H 15 N 3 O 4 ) Example 7 3-Amino-1-(2,4-dichlorophenyl)-4-(2,4- Add 20 ml of ethylene chloride containing 2.23 g of dichlorophenylcarbamoyl (dichlorophenylcarbamoyl)maleimide and 1.7 g of pyridine under cooling with a cryogen (ice-salt).
After 20 ml of ethylene chloride containing 1.06 g of trichloromethyl chloroformate was added dropwise, the mixture was reacted for 20 hours with stirring under cooling with a cryogen (ice-salt). After the reaction, 50 ml of water was added to the resulting reaction mixture while cooling with a cryogen (ice-salt) to separate the mixture into an aqueous layer and an organic layer. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. Ethylene chloride residue
Recrystallize with 30 ml to obtain 3,6-bis(2,4-dichlorophenyl)-2-hydroxy-3,4,6,
7-tetrahydro-4,5,7-trioxo-
0.7 g (30%, decomposition point 262-264°C) of pale yellow needle crystals of 5H-pyrrolo[3,4-d]pyrimidine was obtained. The elemental analysis values are shown below. C H N Cl Analytical value 45.93 1.78 8.67 29.99 Calculated value 45.89 1.50 8.92 30.10 (as C 18 H 7 Cl 4 N 3 O 4 ) Example 8 2.72 g of 3-amino-1-cyclohexyl-4-(cyclohexylcarbamoyl)maleimide 20 ml of ethylene chloride containing 2.27 g of chloroformic acid trichloromethyl ester was added dropwise to 70 ml of ethylene chloride containing 3.37 g of pyridine under cooling with a cryogen (ice-salt), and the mixture was allowed to react for one day while stirring at room temperature. After the reaction, the resulting reaction product mixture was added with water at room temperature.
Add 50 ml and filter, 3,6-dicyclohexyl-2-hydroxy-3,4,6,7-tetrahydro-4,5,7-trioxo-5H-pyrrolo[3,
4-d] 1.35 g (46%) of pyrimidine crystals were obtained. The liquid was separated into an aqueous layer and an organic layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was recrystallized from dioxane to further obtain the target pyrropyrimidine as an adduct with dioxane (molar ratio 2:1). Yield 0.51g (15%).
Decomposition point: 90℃. The elemental analysis values are shown below. C H N Analysis value 61.84 7.22 11.19 Calculated value 61.68 6.99 10.79 (as C 18 H 23 N 3 O 4・1/2C 4 H 8 O 2 )
Claims (1)
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】（R2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
わされるアミノマレイミド類と、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ることを特徴とする 式 （式中、R1は前記と同じ意味を有する。）で表わ
されるピロロピリミジン類の製造法。[Claims] 1 formula [In the formula, R 1 is an alkyl group having 1 to 4 carbon atoms, an alkenyl group having 2 to 4 carbon atoms, a cycloalkyl group having 5 to 7 carbon atoms, an aralkyl group having 7 to 10 carbon atoms, or [Formula] (R 2 represents an alkyl group having 1 to 4 carbon atoms or a halogen atom, and n is 0, 1, 2
Or 3. ) represents a group. ] is characterized by reacting an aminomaleimide represented by the formula with phosgene or chloroformic acid trichloromethyl ester in the presence of pyridine. (In the formula, R 1 has the same meaning as above.) A method for producing pyrrolopyrimidines represented by the formula:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15807481A JPS5859983A (en) | 1981-10-06 | 1981-10-06 | Preparation of pyrrolopyrimidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15807481A JPS5859983A (en) | 1981-10-06 | 1981-10-06 | Preparation of pyrrolopyrimidine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5859983A JPS5859983A (en) | 1983-04-09 |
| JPH0216309B2 true JPH0216309B2 (en) | 1990-04-16 |
Family
ID=15663721
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15807481A Granted JPS5859983A (en) | 1981-10-06 | 1981-10-06 | Preparation of pyrrolopyrimidine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5859983A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0752725Y2 (en) * | 1991-06-17 | 1995-12-06 | 北海道いす▲ず▼自動車株式会社 | Bed heating system for horo type trucks |
-
1981
- 1981-10-06 JP JP15807481A patent/JPS5859983A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0752725Y2 (en) * | 1991-06-17 | 1995-12-06 | 北海道いす▲ず▼自動車株式会社 | Bed heating system for horo type trucks |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5859983A (en) | 1983-04-09 |
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