Br[C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1.CON(C)[C:11](=[O:20])[C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[N:14][C:13]=1[CH3:19].[NH4+].[Cl-]>C1COCC1>[CH3:19][C:13]1[C:12]([C:11]([C:2]2[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=2)=[O:20])=[CH:17][CH:16]=[C:15]([CH3:18])[N:14]=1To a flask containing 5-bromo-1-methyl-1H-imidazole (360 mg, 2.24 mmol) was added THF and the solution was cooled to 0° C. To this clear homogeneous solution was added isopropyl magnesium chloride-LiCl complex (1.3 M, 2.3 mL, 2.98 mmol) which resulted in a white suspension. The reaction mixture was stirred at 0° C. for 30 min, and a THF (2 mL) solution of N-methoxy-N,2,6-trimethylnicotinamide (522 mg, 2.69 mmol, Intermediate 40, step a) was introduced and the mixture was allowed to warm to room temperature for 3 hours and then heated to 50° C. for 20 hours. The contents were cooled to room temperature, poured into a saturated NH4Cl solution and extracted with EtOAc (4×50 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. Flash chromatography on silica gel (25-50% Acetonitrile-DCM increasing gradient to 5% MeOH-DCM) afforded the title compound as a pale yellowish solid.
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