Ammonia → Dabrafenib

Participants

Reaction Conditions

Reaction Steps

A suspension of N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (196 mg, 0.364 mmol) and ammonia in methanol 7M (8 ml, 56.0 mmol) was heated in a sealed tube to 90° C. for 24 h. The reaction was diluted with DCM and added silica gel and concentrated. The crude product was chromatographed on silica gel eluting with 100% DCM to 1:1 [DCM:(9:1 EtOAc:MeOH)]. The clean fractions were concentrated to yield the crude product. The crude product was repurified by reverse phase HPLC (a gradient of acetonitrile:water with 0.1% TFA in both). The combined clean fractions were concentrated then partitioned between DCM and saturated NaHCO3. The DCM layer was separated and dried over Na2SO4. The title compound, N-{3-[5-(2-amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide was obtained (94 mg, 47% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.83 (s, 1 H), 7.93 (d, J=5.2 Hz, 1 H), 7.55-7.70 (m, 1 H), 7.35-7.43 (m, 1 H), 7.31 (t, J=6.3 Hz, 1 H), 7.14-7.27 (m, 3 H), 6.70 (s, 2 H), 5.79 (d, J=5.13 Hz, 1 H), 1.35 (s, 9 H). MS (ESI): 519.9 [M+H]+.

Provenance & Evidence