Tetrahydrofuran → (S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(2,2-difluoroethyl)-2-methyl-1H-imidazole-4-carboxamide

HRID 872936노트

반응식

HRID 872936 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][C@@H:16]([NH:18][C:19]([C:21]3[N:22]=[C:23]([CH3:26])[NH:24][CH:25]=3)=[O:20])[CH3:17])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[F:27][CH:28]([F:31])[CH2:29]I.C(=O)([O-])[O-].[Cs+].[Cs+].C1COCC1>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][C@@H:16]([NH:18][C:19]([C:21]3[N:22]=[C:23]([CH3:26])[N:24]([CH2:29][CH:28]([F:31])[F:27])[CH:25]=3)=[O:20])[CH3:17])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

참가 물질

6

반응물 4

HCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 38335651,1-Difluoro-2-iodoethane3회HCID 178433048HCID 178433048, 화합물

생성물 1

HCID 70657165(S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(2,2-difluoroethyl)-2-methyl-1H-imidazole-4-carboxamide수율 27.4%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

(S)—N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-methyl-1H-imidazole-4-carboxamide (100 mg, 0.271 mmol) was suspended in acetonitrile (5 ml). 1,1-Difluoro-2-iodoethane (0.053 ml, 116 mg) and cesium carbonate (124 mg, 0.380 mmol) were added and the resulting mixture was stirred overnight at RT. Next day 2 ml of THF and 50 μl of 1,1-difluoro-2-iodoethane was added and the stirring was continued for three more nights. Another 0.2 ml of 1,1-difluoro-2-iodoethane was added and the reaction mixture was stirred overnight. The reaction mixture was evaporated. 3 ml of N,N-dimethyl formamide was added and the mixture filtered. Filtrate was purified with LC/MS-trigger. Yield 27.4%. 1H-NMR (400 MHz; CDCl3): δ 1.22 (d, 3H), 2.44 (s, 3H), 4.19-4.33 (m, 3H), 4.39 (dd, 1H), 4.51-4.62 (m, 1H), 5.82-6.13 (m, 1H), 6.61 (d, 1H), 7.49 (d, 1H), 7.52 (s, 1H), 7.64-7.71 (m, 2H), 7.85 (dd, 1H), 8.00 (d, 1H).

후처리

  1. stirringthe reaction mixture was stirred overnight
  2. customThe reaction mixture was evaporated
  3. addition3 ml of N,N-dimethyl formamide was added
  4. filtrationthe mixture filtered
  5. customFiltrate was purified with LC/MS-trigger

출처 및 근거

ORD 기록
ord-09ee73c1385b46aa8269087214d85c81
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08975254B2

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