(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone → HCID 86716148, 화합물

HRID 627568노트

반응식

HRID 627568 반응식
[Li]CCCC.Br[C:7]1[CH:8]=[C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=1)[N:13]=[C:12]([O:18][CH3:19])[C:11]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=1)=[C:10]2[Cl:27].[CH3:28][N:29]1[C:33]([C:34]([C:36]2[CH:37]=[N:38][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:40][CH:41]=2)=[O:35])=[CH:32][N:31]=[CH:30]1>C1COCC1>[Cl:27][C:10]1[C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=[C:7]([C:34]([C:33]3[N:29]([CH3:28])[CH:30]=[N:31][CH:32]=3)([C:36]3[CH:37]=[N:38][C:39]([C:42]([F:44])([F:43])[F:45])=[CH:40][CH:41]=3)[OH:35])[CH:8]=2)[N:13]=[C:12]([O:18][CH3:19])[C:11]=1[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=1

참가 물질

5

반응물 3

HCID 86715442(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone2회HCID 86716096HCID 86716096, 화합물2회HCID 178418339Butyllithium

생성물 1

HCID 86716148HCID 86716148, 화합물

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

n-BuLi (1.6 M in hexane, 2.19 mL, 3.50 mmol) was added over approximately 1 min to a solution of 6-bromo-4-chloro-3-(3-fluorophenyl)-2-methoxy-8-methylquinoline (1.40 g, 3.68 mmol, Intermediate 52) in THF (5 mL) under argon at −78° C. After 1 min, a solution of (1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (939 mg, 3.68 mmol, Intermediate 15, step c) in 5 mL THF under argon was added via cannula. The resulting mixture was stirred at −78° C. for 10 min, then transferred to an ice water bath and stirred 30 min. The reaction was quenched by addition of saturated aqueous NH4Cl, diluted with water and extracted with EtOAc (3×). The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 45-60% CH3CN in [2% conc. aqueous NH4OH in DCM, aqueous phase removed]) to afford the title compound as a white foam.

후처리

  1. customtransferred to an ice water bath
  2. stirringstirred 30 min
  3. customThe reaction was quenched by addition of saturated aqueous NH4Cl
  4. additiondiluted with water
  5. extractionextracted with EtOAc (3×)
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography (silica gel, 45-60% CH3CN in [2% conc. aqueous NH4OH in DCM, aqueous phase removed])

출처 및 근거

ORD 기록
ord-3baa6ec835aa4f2da841fc1f81fc6698
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309222B2

반응 노트

불러오는 중…