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 526853Notes

Reaction equation

HRID 526853 reaction equation
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

Participants

5

Reactant 3

HCID 15152585-Bromo-1-methyl-1H-imidazoleHCID 86716078(2,4-Dichloro-3-phenylquinolin-6-yl)(3-methylisoxazol-5-yl)methanone2×HCID 178418443HCID 178418443, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-1bd67ce6bcb64ff0aa39433779758dad
Source dataset
uspto-grants-2016_05
Patent number
US09346782B2

Reaction notes

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