m-Chloroperbenzoic acid → HCID 24999761, compound

Participants

Reaction Steps

To a room temperature solution of 1-H-tetrazole (0.45M in acetonitrile, 56 mL, 25.3 mmol, solvent removed in vacuo prior to using) in tetrahydrofuran (100 mL) was added example 1, (4-{4-[({3-tert-butyl-1-[3-(hydroxymethyl)phenyl]-1H-pyrazol-5-yl}carbamoyl)amino]-3-fluorophenoxy}-N-methylpyridine-2-carboxamide, (5.00 g, 9.39 mmol) and di-t-butyl N,N-diethylphosphoramidite (2.11 g, 8.45 mmol). The reaction mixture was allowed to stir at room temperature for 2 h. The reaction mixture was then cooled to −40° C. and a slurry of m-chloroperoxybenzoic acid (85% in CH2Cl2, 2.74 g, 12.2 mmol) was added while keeping the reaction temperature below 0° C. The reaction mixture was allowed to warm to room temperature and stir for 10 min and then an aqueous.solution of NaHSO3 (10%, 40 mL) was added. After stirring for an additional 1 h at room temperature, the reaction was transferred to a separatory funnel and extracted with EtOAc. The organic layer was washed with NaHCO3 (2×50 mL), dried (NaSO4) and concentrated. The crude material was purified via column chromatography (CH2Cl2:2 M NH3 in MeOH, 98:2), followed by recrystallization (CH2Cl2/hexanes) to afford 3.57 g (52%) of the desired product as a white crystalline material. MS m/z 724.9 (M+H)+; Retention time (LC-MS): 3.74 min.

Provenance & Evidence