Diisopropylethylamine → (S)-3-(2,5-difluoro-4-(methyl-sulfonyl)phenoxy)-1'-(3-fluoro-5-(trifluoromethyl)pyridin-2-yl)-[1,4'-bipiperidin]-2-one

HRID 408027노트

반응식

HRID 408027 반응식
[F:1][C:2]1[CH:21]=[C:20]([S:22]([CH3:25])(=[O:24])=[O:23])[C:19]([F:26])=[CH:18][C:3]=1[O:4][C@H:5]1[CH2:10][CH2:9][CH2:8][N:7]([CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[C:6]1=[O:17].F[C:28]1[C:33]([F:34])=[CH:32][C:31]([C:35]([F:38])([F:37])[F:36])=[CH:30][N:29]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:21]=[C:20]([S:22]([CH3:25])(=[O:24])=[O:23])[C:19]([F:26])=[CH:18][C:3]=1[O:4][C@H:5]1[CH2:10][CH2:9][CH2:8][N:7]([CH:11]2[CH2:16][CH2:15][N:14]([C:28]3[C:33]([F:34])=[CH:32][C:31]([C:35]([F:38])([F:36])[F:37])=[CH:30][N:29]=3)[CH2:13][CH2:12]2)[C:6]1=[O:17]

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 134215472,3-Difluoro-5-(trifluoromethyl)pyridineHCID 66802663(S)-3-(2,5-Difluoro-4-(methylsulfonyl)phenoxy)-1,4'-bipiperidin-2-one

생성물 1

HCID 86688124(S)-3-(2,5-difluoro-4-(methyl-sulfonyl)phenoxy)-1'-(3-fluoro-5-(trifluoromethyl)pyridin-2-yl)-[1,4'-bipiperidin]-2-one수율 46%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of (S)-3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-[1,4′-bipiperidin]-2-one (Preparation G; 30 mg, 0.077 mmol) in DMF was added 2,3-difluoro-5-(trifluoromethyl)pyridine (42 mg, 0.23 mmol) and DIEA (30 μL, 0.23 mmol) and the reaction was stirred at ambient temperature for 18 hours. The reaction was diluted with EtOAc and washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by preparative TLC (EtOAc/DCM 4:1) to give (S)-3-(2,5-difluoro-4-(methyl-sulfonyl)phenoxy)-1′-(3-fluoro-5-(trifluoromethyl)pyridin-2-yl)-[1,4′-bipiperidin]-2-one as a white solid (20 mg, 0.035 mmol, 46% yield). Mass spectrum (apci) m/z=552.2 (M+H).

후처리

  1. washwashed with brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by preparative TLC (EtOAc/DCM 4:1)

출처 및 근거

ORD 기록
ord-7c34d6fcf58e421d92f0b8c858b77219
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754226B2

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