Isobutylene oxide → HCID 66548285, compound

Participants

Reaction Conditions

Reaction Steps

To slurry of 4-((3S,4S)-4-methyl-1-(methylsulfonyl)pyrrolidin-3-ylamino)-6-(1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide (Example 211, 40 mg, 0.099 mmol) in acetonitrile (0.3 mL) was added DBU (0.060 mL, 0.397 mmol) and 2,2-dimethyloxirane (25.02 mg, 0.347 mmol) and the resulting mixture was heated at 60° C. for ˜16 h. The mixture was cooled, diluted with MeOH, and was purified via preparative reverse-phase HPLC (method B). Fractions which contained the major product were combined and concentrated to give an aqueous solution which was lyophilized to afford a near white solid. This solid was triturated with 1 mL of aq sat. NaHCO3, sonicated, and the resulting solid was collected, rinsed with water and dried on the filter to afford 15 mg (30%) of the title compound as an off-white solid. HPLC (method B) retention time=2.57 min. LCMS (M+1)=476.2. 1HNMR (400 MHz, METHANOL-d4) δ 8.18 (s, 1H), 7.99 (s, 1H), 7.88 (d, J=1.5 Hz, 1H), 7.85 (s, 1H), 7.10 (d, J=1.5 Hz, 1H), 4.98-4.93 (m, 1H), 4.15 (s, 2H), 3.85 (dd, J=10.8, 4.4 Hz, 1H), 3.75 (dd, J=9.8, 7.8 Hz, 1H), 3.58 (dd, J=10.9, 1.7 Hz, 1H), 3.25 (t, J=10.1 Hz, 1H), 2.88 (s, 3H), 2.86-2.77 (m, 1H), 1.27-1.22 (m, 9H).

Provenance & Evidence