Hydrogen chloride-ethyl acetate → Ammonia

Participants

Reaction Steps

Using the general procedure of Example 12, tert-butyl 4-[[5-chloro-4-[(2-methyl-1-oxo-3,4-dihydroisoquinolin-8-yl)amino]pyridin-2-yl]amino]-3-methylpyrazole-1-carboxylate, 68 mg was obtained from tert-butyl 4-amino-3-methylpyrazole-1-carboxylate. To a stirred solution of tert-butyl 4-[[5-chloro-4-[(2-methyl-1-oxo-3,4-dihydroisoquinolin-8-yl)amino]pyridin-2-yl]amino]-3-methylpyrazole-1-carboxylate (68 mg) in EtOAc (0.6 ml) was added HCl/EtOAc (4M, 1.0 ml) and the mixture stirred at room temperature for 2.5 hours. The reaction mixture was diluted with EtOAc (5 ml) and quenched with aq. potassium bicarbonate (0.53 g, 3 ml). The aqueous phase was extracted with EtOAc (2×5 ml), the combined organic extracts dried (Na2SO4), filtered and concentrated under reduced pressure. Purification via a ‘catch and release’ method (2 g isolute flash SCX-2, eluting with 100% MeOH then methanolic ammonia 0.5M→7M) afforded the title compound which was combined with a second batch; 59 mg. 1H NMR spectrum (methanol-d3) 2.03 (s, 3H), 2.84 (t, 2H), 3.00 (s, 3H), 3.46 (t, 2H), 6.47 (s, 1H), 6.72 (dd, 1H), 7.19 (dd, 1H), 7.23 (dd, 1H), 7.44 (bs, 1H), 7.71 (s, 1H); Mass spectrum: ESI+ MH+ 383.

Provenance & Evidence