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 526853노트

반응식

HRID 526853 반응식
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

참가 물질

5

반응물 3

HCID 15152585-Bromo-1-methyl-1H-imidazoleHCID 86716078(2,4-Dichloro-3-phenylquinolin-6-yl)(3-methylisoxazol-5-yl)methanone2회HCID 178418443HCID 178418443, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-1bd67ce6bcb64ff0aa39433779758dad
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346782B2

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