(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone → HCID 86716148、化合物

HRID 627568ノート

反応式

HRID 627568 の反応式
[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

参加物

5

反応物 3

HCID 86715442(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone2 回HCID 86716096HCID 86716096、化合物2 回HCID 178418339Butyllithium

生成物 1

HCID 86716148HCID 86716148、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

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.

後処理

  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])

出典と根拠

ORDレコード
ord-3baa6ec835aa4f2da841fc1f81fc6698
出典データセット
uspto-grants-2016_04
特許番号
US09309222B2

反応ノート

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