(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone → HCID 86716156、化合物

HRID 627575

反応式

HRID 627575 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]([Cl:18])[C:11]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=1)=[C:10]2[Cl:26].[CH3:27][N:28]1[C:32]([C:33]([C:35]2[CH:36]=[N:37][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:39][CH:40]=2)=[O:34])=[CH:31][N:30]=[CH:29]1>C1COCC1>[Cl:18][C:12]1[C:11]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=2)=[C:10]([Cl:26])[C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=[C:7]([C:33]([C:32]3[N:28]([CH3:27])[CH:29]=[N:30][CH:31]=3)([C:35]3[CH:36]=[N:37][C:38]([C:41]([F:43])([F:42])[F:44])=[CH:39][CH:40]=3)[OH:34])[CH:8]=2)[N:13]=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 86716097HCID 86716097、化合物2 回HCID 178418339Butyllithium

生成物 1

HCID 86716156HCID 86716156、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, 1.91 mL, 3.05 mmol) was added over approximately 1 minute to a solution of 6-bromo-2,4-dichloro-3-(3-fluorophenyl)-8-methylquinoline (1.23 g, 3.20 mmol, Intermediate 50, step c) in THF (10 mL) under argon at −78° C. After 1 minute, a solution of (1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (817 mg, 3.20 mmol, Intermediate 15, step c) in 10 mL THF under argon was added via cannula. The resulting mixture was stirred at −78° C. for 10 minutes, then transferred to an ice water bath and stirred 1 hour. 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 cream colored solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.83 (s, 1H), 8.14 (dd, J=1.83, 7.46 Hz, 1H), 7.92 (d, J=8.31 Hz, 1H), 7.65 (d, J=8.31 Hz, 1H), 7.57-7.62 (m, 1H), 7.44-7.53 (m, 1H), 7.20 (td, J=2.20, 8.31 Hz, 1H), 7.09 (t, J=6.60 Hz, 1H), 7.01-7.07 (m, 1H), 6.29 (d, J=0.98 Hz, 1H), 6.02 (br. s., 1H), 3.37 (s, 3H), 2.74 (s, 3H). MS m/e 561.2 [M+H]+.

後処理

  1. customtransferred to an ice water bath
  2. stirringstirred 1 hour
  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-751341c9db7a403bba38f8b7633fe645
出典データセット
uspto-grants-2016_04
特許番号
US09309222B2

関連ノート

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