2-Fluoroaniline → 4-chloro-2-fluoro-N-(2-fluorophenyl)-5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]benzenesulfonamide

HRID 400520

반응식

HRID 400520 반응식
[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([S:12](Cl)(=[O:14])=[O:13])=[CH:7][C:3]=1[C:4](Cl)=[O:5].[CH2:16]1[NH:21][CH2:20][CH2:19][N:18]2[CH2:22][CH2:23][CH2:24][C@@H:17]12.C(=O)([O-])[O-].[Na+].[Na+].[F:31][C:32]1[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=1[NH2:34]>ClCCl.CO>[Cl:1][C:2]1[C:3]([C:4]([N:21]2[CH2:20][CH2:19][N:18]3[CH2:22][CH2:23][CH2:24][C@H:17]3[CH2:16]2)=[O:5])=[CH:7][C:8]([S:12]([NH:34][C:33]2[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=2[F:31])(=[O:14])=[O:13])=[C:9]([F:11])[CH:10]=1

참가 물질

7

반응물 4

HCID 95842-FluoroanilineHCID 10340Sodium Carbonate2회HCID 781249(6S)-1,4-Diazabicyclo(4.3.0)nonaneHCID 866439242-Chloro-5-(chlorosulfonyl)-4-fluorobenzoyl chloride

생성물 1

HCID 468524404-chloro-2-fluoro-N-(2-fluorophenyl)-5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]benzenesulfonamide

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매4회

실험 절차

To crude 2-chloro-5-(chlorosulfonyl)-4-fluorobenzoyl chloride (4 mmol) in anhydrous dichloromethane (100 mL) was added (S)-octahydropyrrolo[1,2-a]pyrazine (0.505 g, 4 mmol) in dichloromethane (10 mL) slowly over 10 minutes at room temperature. Then sodium carbonate (0.933 g, 8.8 mmol) was added. The mixture was stirred at room temperature overnight. Then dichloromethane was removed by concentration in vacuo, and 2-fluoroaniline (4.44 g, 40 mmol) in dichloromethane (30 mL) was added. The mixture was stirred at room temperature for 4 days. At that time, sodium carbonate (0.42 g, 4 mmol) and methanol (20 mL) were added, the mixture was stirred for 30 minutes, then filtered, and concentrated. The residue was purified by chromatography on silica gel (ethyl acetate, then methanol/ethyl acetate=1:15) to give the titled compound: 1H NMR (500 MHz, DMSO-d6) δ ppm 1.20-1.38 (m, 1H), 1.60-2.20 (m, 7H), 2.80-3.40 (m, 4H), 4.40-4.60 (m, 1H), 7.20 (m, 4H), 7.60 (m, 1H), 7.88 (m, 1H), 10.60 (br s, 1H); MS (ESI) m/z 456 (M+H)+.

후처리

  1. additionwas added
  2. stirringThe mixture was stirred at room temperature for 4 days
  3. stirringthe mixture was stirred for 30 minutes
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica gel (ethyl acetate

출처 및 근거

ORD 기록
ord-6e875489de3d4759b43dbb3d08b1ff41
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08741899B2

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