p-Toluenesulfonic acid monohydrate → 3-[3-(2-{[4-(1,4'-bipiperidin-1'-yl)-2-(methyloxy)phenyl]amino}-4-pyrimidinyl)-7-fluoroimidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)benzamide

Participants

Reaction Conditions

Reaction Steps

To 3-[3-(2-chloro-4-pyrimidinyl)-7-fluoroimidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluoro-phenyl)benzamide (Example 194, step B) (100 mg, 0.21 mmol) and 4-(1,4′-bipiperidin-1′-yl)-2-(methyloxy)aniline (Example 22, step C) (54 mg, 0.19 mmol) in 2,2,2-trifluoroethanol (2 mL) was added p-toluenesulfonic acid monohydrate (95 mg, 0.50 mmol). The mixture was stirred and heated on a microwave at 150° C. for 30 min, then cooled to rt. The mixture was neutralized with 0.5M sodium methoxide in MeOH. The mixture was concentrated under vacuum and the residue purified by silica gel chromatography to give a yellow oil. The oil was dissolved in minimal DCM, then hexane was added until a precipitate was formed. The slurry was cooled at −10° C. for 30 min, then poured through a Teflon filter, washing the solids with cold hexanes. The solids were dried under vacuum to give the title compound (84 mg, 0.11 mmol, 62%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 9.48 (br s, 1H), 8.51 (s, 1H), 8.32 (s, 1H), 8.20 (d, 1H, J=5.13 Hz), 8.06 (d, 1H, J=7.88 Hz), 7.82 (d, 1H, J=7.88 Hz), 7.59-7.64 (m, 2H), 7.35-7.45 (m, 2H), 7.21 (t, 2H, J=8.06 HZ), 7.01-7.09 (m, 1H), 6.67-6.69 (m, 1H), 6.43-6.51 (m, 2H), 3.70-3.81 (m, 5H), 2.65 (t, 2H, J=11.36 Hz), 2.42-2.48 (m, 4H), 2.29-2.37 (m, 1H), 1.75-1.83 (m, 2H), 1.44-1.59 (m, 6H), 1.34-1.41 (m, 2H). MS (ESI): 733 [M+H]+.

Provenance & Evidence