Diisopropylethylamine → 8-Fluoro-11-{3-[2-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-2-trifluoromethyl-5H-dibenzo[b,e][1,4]diazepine

HRID 1350535ノート

反応式

HRID 1350535 の反応式
Cl.[F:2][C:3]1[CH:4]=[CH:5][C:6]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[CH:16][C:10]=3[C:9]([NH2:21])=[N:8][C:7]=2[CH:22]=1.C(N(C(C)C)CC)(C)C.[F:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][CH2:40][CH:41]2[CH2:46]N[CH2:44][CH2:43][NH:42]2)=[CH:35][CH:34]=1>CN1CCCC1=O.C(OCC)(=O)C>[F:2][C:3]1[CH:4]=[CH:5][C:6]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([C:17]([F:18])([F:20])[F:19])=[CH:16][C:10]=3[C:9]([N:21]3[CH2:44][CH2:43][NH:42][CH:41]([CH2:40][CH2:39][C:36]4[CH:37]=[CH:38][C:33]([F:32])=[CH:34][CH:35]=4)[CH2:46]3)=[N:8][C:7]=2[CH:22]=1

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 178109312-[2-(4-Fluorophenyl)ethyl]piperazineHCID 1357977638-Fluoro-2-trifluoromethyl-5h-dibenzo[b,e][1,4]diazepin-11-ylaminehydrochloride

生成物 1

HCID 1357977548-Fluoro-11-{3-[2-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-2-trifluoromethyl-5H-dibenzo[b,e][1,4]diazepine収率 28.3%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
195 °C

実験手順

Heat a solution of 8-fluoro-2-trifluoromethyl-5H-dibenzo[b,e][1,4]diazepin-11-ylamine hydrochloride (0.2 g, 0.60 mmol) and diisopropylethylamine (0.086 g, 0.66 mmol) in 1-methyl-2-pyrrolidinone (4 mL) to 60° C. After 30 minutes, add 2-[2-(4-fluoro-phenyl)-ethyl]-piperazine (0.38 g, 1.81 mmol) and heat the reaction mixture to 195° C. for 16 hours. Cool reaction mixture to ambient temperature. Dilute with of ethyl acetate (50 ml) and wash twice with saturated aqueous sodium chloride then twice with water. Collect the organic layer and dry over sodium sulfate. Remove solvent under reduced pressure. Purification via flash chromatography, eluting with a linear gradient starting with 100% dichloromethane and going to 85% of dichloromethane with 15% 2M ammonia in methanol, gives the free base of the title compound (0.083 g, 0.17 mmol, 28% yield) as a yellow amorphous solid: Mass Spectrum (m/e): 487(M+1).

後処理

  1. temperatureCool
  2. customreaction mixture to ambient temperature
  3. washwash twice with saturated aqueous sodium chloride
  4. customCollect the organic layer
  5. dry with materialdry over sodium sulfate
  6. customPurification via flash chromatography
  7. washeluting with a linear gradient

出典と根拠

ORDレコード
ord-fa7b3d6dfea540159183632721f50086
出典データセット
uspto-grants-2007_05
特許番号
US07214673B2

反応ノート

読み込み中…