Diisopropylethylamine → HCID 117868325, compound

Participants

Reaction Steps

A 200 uL aliquot of HATU (23.41 mg, 0.062 mmol) and diisopropylethylamine (21.51 μl, 0.123 mmol) were added to a 200 uL aliquot of 4-(6-azaspiro[3.4]octan-8-ylamino)-6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide HBr (from Step 6, 15 mg, 0.041 mmol) and cyclopropane carboxylate (1.5 equiv.) in DMF. The reaction was stirred for 3 h at room temperature. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 0-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to afford the title compound (3.9 mg). 1H NMR (500 MHz, METHANOL-d4/CDCl3) δ 8.11 (d, J=11.9 Hz, 1H), 7.80 (d, J=9.9 Hz, 1H), 7.78-7.71 (m, 2H), 6.91 (dd, J=14.1, 1.7 Hz, 1H), 4.83-4.75 (m, 1H), 4.13 (dd, J=10.4, 5.0 Hz, 1H), 4.07-3.99 (m, 1H), 3.96 (s, 1.5H), 3.94 (s, 1.5H), 3.98-3.76 (m, 2H), 2.37 (dd, J=11.1, 7.2 Hz, 1H), 2.28-1.95 (m, 5H), 1.12-0.70 (m, 4H)

Provenance & Evidence