Dimethylamine → HCID 66548110, compound

Participants

Reaction Steps

To solution of 5-(3-carbamoyl-4-((3S,4S)-1-(1-cyanocyclopropanecarbonyl)-4-methylpyrrolidin-3-ylamino)pyrrolo[1,2-b]pyridazin-6-yl)picolinic acid (15 mg, 0.026 mmol), DIPEA (0.018 mL, 0.102 mmol) and BOP (16.94 mg, 0.038 mmol) in DMF (0.3 mL) was added a 2 M solution of dimethylamine in THF (0.026 mL, 0.051 mmol) and the resulting mixture was stirred for 1 h. The mixture was concentrated to remove the THF and was purified by preparative LC/MS with the following conditions: column: Waters XBridge C18, 19×200 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: 10-100% B over 15 minutes, then a 7-minute hold at 100% B; Flow: 25 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to afford 7.2 mg of the title compound. LCMS (method H) retention time=1.78 min. (MH+501.2). 1H NMR (500 MHz, METHANOL-d4, appeared as rotomers) δ 9.06 (dd, J=7.9, 1.5 Hz, 1H), 8.40-8.29 (m, 2H), 8.22 (dd, J=11.1, 1.7 Hz, 1H), 7.80 (d, J=7.9 Hz, 1H), 7.47-7.34 (m, 1H), 5.28-5.04 (m, 1H), 4.58-4.42 (m, 2H), 4.13-3.87 (m, 2H), 3.64-3.52 (m, 1H), 3.34-3.26 (m, 6H), 3.09-2.89 (m, 1H), 2.01-1.83 (m, 1H), 1.80-1.59 (m, 3H), 1.51-1.35 (m, 3H).

Provenance & Evidence