Methanesulfonyl chloride → HCID 59321424, compound

Participants

Reaction Steps

3-Fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)-N-((4-phenylpiperidin-4-yl)methyl)picolinamide (crude from deprotection of 3-fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)-N-((4-phenylpiperidin-4-yl)methyl)picolinamide, 0.042 g, 0.066 mmol) was diluted in NMP (1 mL) and treated with methanesulfonyl chloride (0.010 g, 0.086 mmol) and diisopropylethylamine (0.059 mL, 0.331 mmol) at 23° C. The reaction was stirred overnight, then diluted in 10% water in acetonitrile+0.05% TFA and purified on preparative HPLC (acetonitrile/water/trifluoroacetic acid). The fractions containing the desired product were evaporated and the residue was diluted with DMF and applied on a SCX SPE cartridge. This was washed with methanol and eluted with 2M ammonia/methanol/THF. The fractions containing the desired product were concentrated to give a solid (0.0129 g, 32%) which was triturated with ethyl ether, suspended in acetonitrile and treated with a 0.1N hydrochloric acid/methanol solution (0.210 mL). The solution was diluted with water and concentrated on speedvac to give the HCl salt of the title material. 1H NMR (400 MHz, DMSO-d6) δ ppm: 1.92 (1H, ddd, J=13.58, 10.04 and 3.41 Hz), 2.25 (2H, dd, J=13.14 and 3.79 Hz), 2.31 (3H, s), 2.76-2.84 (4H, m), 2.86 (3H, s), 6.84-6.88 (1H, br d), 6.93 (1H, s), 7.03 (1H, t, J=5.31 Hz), 7.11-7.16 (2H, m), 7.23-7.29 (2H, m), 7.36-7.45 (3H, m), 7.81 (1H, s), 8.17 (1H, d, J=5.05 Hz), 8.22 (1H, d, J=5.05 Hz), 8.28 (1H, t, J=6.32 Hz), 11.84 (1H, s). LC/MS (M+H)+: 613. HPLC ret. time (Condition C): 5.588 min.

Provenance & Evidence