Cyclopropanecarboxylic acid → (S)-8-chloro-1-[5-(cyclopropyl)-1,2,4-oxadiazol-3-yl]-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

HRID 867550ノート

反応式

HRID 867550 の反応式
[CH:1]1([C:4]([OH:6])=O)[CH2:3][CH2:2]1.[Cl:7][C:8]1[C:13]2[C:14](=[O:29])[N:15]3[CH2:28][CH2:27][CH2:26][C@H:16]3[C:17]3[N:18]([CH:19]=[N:20][C:21]=3[C:22](=[N:24]O)[NH2:23])[C:12]=2[CH:11]=[CH:10][CH:9]=1>CN(C)C=O>[Cl:7][C:8]1[C:13]2[C:14](=[O:29])[N:15]3[CH2:28][CH2:27][CH2:26][C@H:16]3[C:17]3[N:18]([CH:19]=[N:20][C:21]=3[C:22]3[N:24]=[C:4]([CH:1]4[CH2:3][CH2:2]4)[O:6][N:23]=3)[C:12]=2[CH:11]=[CH:10][CH:9]=1

参加物

4

反応物 2

HCID 15655Cyclopropanecarboxylic acidHCID 53703069(S)-8-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxamidoxime

生成物 1

HCID 54012187(S)-8-chloro-1-[5-(cyclopropyl)-1,2,4-oxadiazol-3-yl]-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

17.0 g (105 mmol) of N,N'-carbonyldiimidazole are added portionwise to a solution of 8.61 g (100 mmol) of cyclopropanecarboxylic acid in 30 ml of N,N-dimethylformamide. The mixture is stirred at room temperature for 1 hour and then heated rapidly to 50°. The solution obtained is added to a suspension of 33.1 g (100 mmol) of (S)-8-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxamidoxime in 100 ml of N,N-dimethylformamide and the mixture is heated to 90° for 2.5 hours. The solvent is removed on a rotary evaporator and is replaced by 100 ml of acetic acid. After stirring at 120° for 2.5 hours the mixture is again evaporated, the residue is dissolved in methylene chloride and washed with saturated sodium bicarbonate solution. The organic phase is dried over magnesium sulphate and concentrated. By chromatography of the oily residue on silica gel while eluting with ethyl acetate and recrystallization from alcohol and a small amount of methylene chloride there is obtained (S)-8-chloro-1-[5-(cyclopropyl)-1,2,4-oxadiazol-3-yl]-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one of melting point 236°-237°

後処理

  1. temperatureheated rapidly to 50°
  2. customThe solution obtained
  3. temperaturethe mixture is heated to 90° for 2.5 hours
  4. customThe solvent is removed on a rotary evaporator
  5. stirringAfter stirring at 120° for 2.5 hours the mixture
  6. customis again evaporated
  7. dissolutionthe residue is dissolved in methylene chloride
  8. washwashed with saturated sodium bicarbonate solution
  9. dry with materialThe organic phase is dried over magnesium sulphate
  10. concentrationconcentrated
  11. washBy chromatography of the oily residue on silica gel while eluting with ethyl acetate and recrystallization from alcohol

出典と根拠

ORDレコード
ord-1ac2b008adfd4bbe8d9f85adc7dc5cec
出典データセット
uspto-grants-1988_10
特許番号
US04775671

反応ノート

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