Hydrochloric Acid → 7-chloro-3-(3,3-dicyclopropyl-3-hydroxy-1-propynyl)-4,5-dihydro-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one

HRID 1606991

反応式

HRID 1606991 の反応式
[Cl:1][C:2]1[C:7]2[C:8](=[O:19])[N:9]([CH3:18])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]#[CH:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[CH:25]1([C:28]([CH:30]2[CH2:32][CH2:31]2)=[O:29])[CH2:27][CH2:26]1.Cl>O1CCCC1.CCCCCC.O.CN(C)P(=O)(N(C)C)N(C)C>[Cl:1][C:2]1[C:7]2[C:8](=[O:19])[N:9]([CH3:18])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]#[C:17][C:28]([CH:30]3[CH2:32][CH2:31]3)([CH:25]3[CH2:27][CH2:26]3)[OH:29])[C:6]=2[CH:5]=[CH:4][CH:3]=1

参加物

9

反応物 4

HCID 313Hydrochloric AcidHCID 70721Dicyclopropyl ketoneHCID 198515337-chloro-3-ethynyl-4,5-dihydro-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-oneHCID 178418339Butyllithium

生成物 1

HCID 198515587-chloro-3-(3,3-dicyclopropyl-3-hydroxy-1-propynyl)-4,5-dihydro-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒HCID 12679Hexamethylphosphoramide溶媒

実験手順

4.07 g (15 mmol) of 7-chloro-3-ethynyl-4,5-dihydro-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one was suspended in 30 ml of tetrahydrofuran and treated dropwise within 35 minutes at a maximum of -5° with 20 ml (30 mmol) of 1.6M butyllithium in hexane. After stirring in an ice-bath for 1.5 hours the mixture was cooled to -74° and there are added thereto 5 ml of hexamethylphosphoric acid triamide and, after 10 minutes, 3.30 g (30 mmol) of dicyclopropyl ketone. The mixture was left to come to room temperature during 6 hours and was stirred over the weekend. The reaction mixture was then poured into 200 ml of water, acidified to pH 7 with 4N hydrochloric acid and extracted four times with ethyl acetate. The combined organic extracts were washed twice with water, dried over magnesium sulphate and evaporated. After chromatography of the residue on silica gel while eluting with methylene chloride/methanol (19:1) and subsequent recrystallization from ethyl acetate there was obtained 7-chloro-3-(3,3-dicyclopropyl-3-hydroxy-1-propynyl)-4,5-dihydro-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one of melting point 179°-181°.

後処理

  1. temperaturewas cooled to -74°
  2. additionthere are added
  3. waitThe mixture was left
  4. waitto come to room temperature during 6 hours
  5. stirringwas stirred over the weekend
  6. extractionextracted four times with ethyl acetate
  7. washThe combined organic extracts were washed twice with water
  8. dry with materialdried over magnesium sulphate
  9. customevaporated
  10. washAfter chromatography of the residue on silica gel while eluting with methylene chloride/methanol (19:1) and subsequent recrystallization from ethyl acetate

出典と根拠

ORDレコード
ord-94a0aef4069845669ba48baec097306e
出典データセット
uspto-grants-1989_09
特許番号
US04863920

関連ノート

読み込み中…