Methanesulfonic Acid → HCID 178505360, compound

Participants

Reaction Steps

To (R)-(1-(2-(1-(4-chloro-1H-pyrazol-1-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone (Example 109-A, 100 g), prepared by the alternative method described in Example 109-A (Step 1 and Step 2), was added acetonitrile (500 mL). The mixture was stirred for 5 min at room temperature before adding methanesulfonic acid (14.38 mL, 219.29 mmol) over a period of 15 sec. The mixture was stirred for 2 h while cooling back to 19° C. The solids were filtered and washed with acetonitrile (250 mL) and dried under nitrogen for 18 h to afford the title compound (86 g, 73% over two steps from Step 2, alternative method for Example 109-A) as a white solid. HPLC retention time: 4.451 min (Method: Same as for Step 1 in the alternative method described for Example 109-A). Chiral HPLC retention time: 3.837 min (Method: Column: OJ-H 4.6×250 mm, 5 μm; S10|(5): acetonitrile+0.1% isopropylamine, 150 bar, 4 mL/min, 40° C., 0-5.5 min: 5-45% S, 5.5-7.5 min: 45% S, 7.51-8 min: 5% S). 1H NMR (400 MHz, DMSO-d6) δ 1.35-2.03 (m, 12H), 2.32 (s, 3H), 2.53-2.65 (m, 1H), 2.91-3.13 (m, 2H), 3.20-3.35 (m, 2H), 3.35-3.55 (m, 2H), 4.20-4.36 (m, 2H), 7.05 (d, 1H), 7.73 (s, 1H), 7.83 (d, 1H), 8.30 (s, 1H).

Provenance & Evidence