Dichloromethane → (2S,4S)-4-{4-[6-Amino-5-(5-chloro-8-fluoroisoquinolin-3-yl)-pyridin-3-yl]-pyrazol-1-yl}-pyrrolidine-2-carboxylic acid dimethylamide

Participants

Reaction Steps

To a solution of (2S,4S)-4-{4-[6-amino-5-(5-chloro-8-fluoroisoquinolin-3-yl)-pyridin-3-yl]-pyrazol-1-yl}-pyrrolidine-2-carboxylic acid (5.00 mg, 0.00889 mmol) in DCM (2 mL, 0.02 mol) was added dimethylamine hydrochloride (20 mg, 0.2 mmol) and DIPEA (0.2 mL, 1.0 mmol), and stirred for 1 min. TBTU (5.71 mg, 0.0178 mmol) was then added, and the solution was stirred at rt for 10 min. The material was transferred to a separatory funnel. The organic layer was washed with water, and concentrated in vacuo. The material was loaded onto a prep TLC plate, eluting with 6% (7N NH3 in MeOH/DCM. The band containing the product was collected and the product was eluted with 1:1 MeOH/DCM. The solution was concentrated in vacuo to afford the title compound as a yellow solid. 1H NMR (400 MHz, CD3OD): δ=2.15-2.22 (m, 1H), 2.82-2.90 (m, 1H), 2.99 (s, 3H), 3.10-3.13 (m, 3H), 3.21-3.26 (m, 1H), 3.49 (dd, J=12.3, 3.2 Hz, 1H), 4.15 (t, J=8.2 Hz, 1H), 4.99-5.05 (m, 1H), 7.38 (dd, J=9.6, 8.3 Hz, 1H), 7.84-7.91 (m, 2H), 8.13-8.17 (m, 2H), 8.27 (d, J=2.3 Hz, 1H), 8.43 (s, 1H), 9.60 (s, 1H). MS (ES+): m/z=480.13/482.11 (100/36) [MH+]. HPLC: tR=1.89 min (ZQ2, polar—5 min).

Provenance & Evidence