Hydrochloric Acid → (R)-N-(1-(5-Chloro-2-((1-methyl-1H-pyrazol-4-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl)acrylamide

Participants

Reaction Steps

A solution of 4 M HCl in 1,4-dioxane (0.31 mL, 1.3 mmol) was added to a solution of tert-butyl (1-{5-chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}piperidin-3-yl)carbamate (56 mg, 0.12 mmol) in methanol (1.3 mL). After 24 hrs, the mixture was concentrated to dryness by rotary evaporation. The resulting residue was suspended in EtOAc (2.5 mL) and saturated aqueous sodium bicarcarbonate solution (1.3 mL). Acryloyl chloride (13 μL, 0.16 mmol) was added and the mixture was stirred for 1 hr. The organic layer was separated, dried over MgSO4 and evaporated to give the title compound (39 mg, 69% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.40 (br. s., 1H), 8.76 (s, 1H), 8.14 (d, J=7.82 Hz, 1H), 7.83 (s, 1H), 7.47 (s, 1H), 7.05 (d, J=2.45 Hz, 1H), 6.19-6.31 (m, 1H), 6.07-6.16 (m, 1H), 5.60 (dd, J=10.03, 2.45 Hz, 1H), 4.13 (d, J=12.23 Hz, 1H), 4.03 (d, J=12.72 Hz, 1H), 3.85-3.98 (m, 1H), 3.77 (s, 3H), 2.96 (t, J=11.25 Hz, 1H), 2.80 (t, J=11.13 Hz, 1H), 1.89-2.00 (m, 1H), 1.79-1.88 (m, 1H), 1.67-1.79 (m, 1H), 1.40-1.57 (m, 1H). m/z (APCI+) for C18H21ClN8O 401.2 (M+H)+.

Provenance & Evidence