Methanesulfonic Acid → HCID 42598186, compound

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Reaction Steps

To 4-amino-5-(3-fluoro-4-{[(6-methylpyridin-2-yl)carbamoyl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide (5.9 g) was added THF (650 mL). The mixture was heated until dissolution took place (up to 80° C.). In a separate flask methane sulfonic acid (2.5 mL) was diluted with THF (25 mL). 17 mL of the methane sulfonic acid solution in THF was added to the solution of 4-amino-5-(4-{[(6-methylpyridin-2-yl)carbamoyllamino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide in THF. The mixture was left to stir for 16 h. The solid was filtered using a 0.2 uM membrane filter. The solid was dried to give 7.91 g (97%) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.68 (t, 1H), 8.60 (br s, 1H), 8.38 (t, 1H), 8.30 (s, 1H), 8.03 (s, 1H), 7.70 (t, 1H), 7.30 (d, 1H), 7.18 (d, 1H), 7.02 (bd, 1H), 6.85 (d, 1H), 3.98 (m, 2H), 2.54 (s, 3H), 2.32 (s, 6H); ES-MS m/z 503.30 (MH)+, HPLC RT (Method A) 2.64 min. DSC mp.=249.97° C. (after stirring in MeOH for 1 Week and drying mp.=258.99° C.) Anal. Calc'd for C22H18F4N8O2.2(CH4O3S): C, 41.50%; H, 3.77%; F, 10.94%; N, 16.13%; O, 18.43%; S, 9.23%. Found: C, 41.21%; H, 3.51%; N, 15.69%. Karl Fischer Titration: 0.96% water.

Provenance & Evidence