5-Bromo-1-methyl-1H-imidazole → (2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(3-methylisoxazol-5-yl)methanol

HRID 526853ノート

反応式

HRID 526853 の反応式
C([Mg]Br)C.Br[C:6]1[N:10]([CH3:11])[CH:9]=[N:8][CH:7]=1.[Cl:12][C:13]1[C:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[C:21]([Cl:29])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:30]([C:32]3[O:36][N:35]=[C:34]([CH3:37])[CH:33]=3)=[O:31])[CH:19]=2)[N:14]=1>C(Cl)Cl>[Cl:12][C:13]1[C:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[C:21]([Cl:29])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:30]([C:6]3[N:10]([CH3:11])[CH:9]=[N:8][CH:7]=3)([C:32]3[O:36][N:35]=[C:34]([CH3:37])[CH:33]=3)[OH:31])[CH:19]=2)[N:14]=1

参加物

5

反応物 3

HCID 15152585-Bromo-1-methyl-1H-imidazoleHCID 86716078(2,4-Dichloro-3-phenylquinolin-6-yl)(3-methylisoxazol-5-yl)methanone2 回HCID 178418443HCID 178418443、化合物

生成物 1

HCID 117869589(2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(3-methylisoxazol-5-yl)methanol

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

Ethylmagnesium bromide (3 M in Et2O, 0.064 mL, 0.193 mmol) was added dropwise to a solution of 5-bromo-1-methyl-1H-imidazole (31.0 mg, 0.193 mmol) in DCM (1 mL) under a nitrogen atmosphere. The mixture was stirred at room temperature for 15 minutes, then was cooled to 0° C. A solution of (2,4-dichloro-3-phenylquinolin-6-yl)(3-methylisoxazol-5-yl)methanone (49.2 mg, 0.128 mmol, Intermediate 3: step b) in DCM (2 mL) was added via cannula. The mixture was stirred at room temperature for 2 hours. The reaction was quenched by addition of saturated aqueous NH4Cl and was diluted with water. The mixture was extracted three times with EtOAc. The organic phase was dried (Na2SO4), filtered, and concentrated to dryness. The crude product was purified by RP-HPLC (10-90% CH3CN—H2O, 0.1% TFA) to afford the title compound along with the intended product (2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(3-methylisoxazol-5-yl)methanol. 1H NMR (400 MHz, DMSO-d6) δ 8.41 (s, 1H), 8.06 (d, J=9.05 Hz, 1H), 7.92 (d, J=8.80 Hz, 1H), 7.47-7.63 (m, 3H), 7.36-7.47 (m, 2H), 6.53 (br. s., 1H), 6.34 (s, 1H), 2.23-2.38 (m, 2H), 2.20 (s, 3H), 0.76 (t, J=7.21 Hz, 3H); MS m/e 413.1 (M+H)+.

後処理

  1. temperaturewas cooled to 0° C
  2. stirringThe mixture was stirred at room temperature for 2 hours
  3. customThe reaction was quenched by addition of saturated aqueous NH4Cl
  4. additionwas diluted with water
  5. extractionThe mixture was extracted three times with EtOAc
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe crude product was purified by RP-HPLC (10-90% CH3CN—H2O, 0.1% TFA)

出典と根拠

ORDレコード
ord-1bd67ce6bcb64ff0aa39433779758dad
出典データセット
uspto-grants-2016_05
特許番号
US09346782B2

反応ノート

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