Dimethylcarbamoyl Chloride → Hydrochloric Acid

Participants

Reaction Steps

3-(4-(1-Cyclopentylpiperidin-4-yl)phenylamino)-5-((3aR,7aR)-dihydro-1H-pyrrolo[3,2-b]pyridin-4(2H,5H,6H,7H,7aH)-yl)pyrazine-2-carboxamide (420) (82 mg, 0.16 mmol) was dissolved in 3 mL NMP. To it were added DIEA (290 μL, 1.68 mmol) and then dimethylcarbamoyl chloride (62 μL, 0.67 mmol). The mixture was stirred at RT for 2 hours, quenched with 0.5 mL TFA, and subjected to reverse phase prep HPLC using 5 mM HCl (aq) and neat MeCN as mobile phases to isolate (3aR,7aR)-4-(5-carbamoyl-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-N,N-dimethyloctahydro-1H-pyrrolo[3,2-b]pyridine-1-carboxamide (421) as HCl salt (61 mg, 64%). LC-MS (ESI): m/z (M+1) 561.9. UV: λ=267, 275, 304, 334, 372 nm. Proton NMR (CD3OD): δ 7.64 (1H, m), 7.59 (2H, d, J=7.5 Hz), 7.20 (2H, d, J=8.0 Hz), 4.18 (2H, m), 3.71 (3H, m), 3.61-3.56 (2H, m), 3.44 (1H, m), 3.13 (3H, m), 2.90 (7H, s), 2.21 (3H, m), 2.15 (2H, m), 2.07 (1H, m), 1.95 (3H, m), 1.87 (3H, m), 1.73 (4H, m), 1.61 (2H, m) ppm.

Provenance & Evidence