4-(Trifluoromethyl)aniline → 4-chloro-3-[(8aR)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]-N-[4-(trifluoromethyl)phenyl]benzenesulfonamide

HRID 1951501

반응식

HRID 1951501 반응식
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([S:11](Cl)(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4](Cl)=[O:5].[CH2:15]1[NH:20][CH2:19][CH2:18][N:17]2[CH2:21][CH2:22][CH2:23][C@H:16]12.C(=O)([O-])[O-].[Na+].[Na+].[F:30][C:31]([F:40])([F:39])[C:32]1[CH:38]=[CH:37][C:35]([NH2:36])=[CH:34][CH:33]=1>ClCCl.CO>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([S:11]([NH:36][C:35]2[CH:37]=[CH:38][C:32]([C:31]([F:30])([F:39])[F:40])=[CH:33][CH:34]=2)(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4]([N:20]1[CH2:19][CH2:18][N:17]2[CH2:21][CH2:22][CH2:23][C@@H:16]2[CH2:15]1)=[O:5]

참가 물질

7

반응물 4

HCID 99644-(Trifluoromethyl)anilineHCID 10340Sodium Carbonate2회HCID 7004239(8aR)-Octahydropyrrolo(1,2-a)pyrazineHCID 545501992-Chloro-5-(chlorosulfonyl)benzoyl chloride

생성물 1

HCID 468516554-chloro-3-[(8aR)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]-N-[4-(trifluoromethyl)phenyl]benzenesulfonamide

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매3회

실험 절차

To crude 2-chloro-5-(chlorosulfonyl)benzoyl chloride (2 mmol) in anhydrous dichloromethane (50 mL) was added (R)-octahydropyrrolo[1,2-α]pyrazine (0.252 g, 2 mmol) in dichloromethane (4 mL) slowly over 10 minutes at room temperature. Then sodium carbonate (0.46 g, 4.4 mmol) was added. The mixture was stirred at room temperature overnight. Then dichloromethane was removed by concentration, and 4-(trifluoromethyl)aniline (3.22 g, 20 mmol) was added. The mixture was stirred at 70° C. overnight. Then sodium carbonate (0.21 g, 2 mmol) and methanol (5 mL) were added at room temperature. 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=1:10) to give the titled compound: 1H NMR (500 MHz, DMSO-d6) δ ppm 1.30 (m, 1H), 1.55 (m, 1H), 1.70-2.00 (m, 4H), 2.60 (m, 2H), 2.80-3.50 (m, 4H), 4.40-4.60 (m, 1H), 7.30 (m, 2H), 7.62 (m, 2H), 7.82 (m, 3H), 11.00 (br s, 1H); MS (ESI) m/z 488 (M+H)+.

후처리

  1. additionwas added
  2. stirringThe mixture was stirred at 70° C. overnight
  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-452b663ebbd143318b1c07c27fb7df85
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08404719B2

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