Triethylamine → (3S,4S)-tert-butyl 3-((3-carbamoyl-6-(3-methylisoxazol-5-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of (3S,4S)-tert-butyl 3-((3-carbamoyl-6-ethynylpyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate from Step 2 (88 mg, 0.221 mmol) in dichloromethane (2 mL) and triethylamine (0.046 mL, 0.332 mmol) was added (Z)—N-hydroxyacetimidoyl chloride (25.9 mg, 0.277 mmol). The solution was stirred at 40° C. overnight. After stirring overnight, the reaction was cooled to room temperature and diluted with dichloromethane. This solution was washed once with aqueous potassium carbonate, and once with water. It was then dried over sodium sulfate, filtered and concentrated. The crude material was purified by flash chromatography, eluting with 0-100% ethyl acetate in hexanes. Concentration of the pure fractions afforded the title compound (64 mg, 60.4% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.20 (t, J=9.1 Hz, 1H), 8.31 (s, 1H), 8.24 (d, J=1.3 Hz, 1H), 7.30 (br. s., 1H), 6.72 (s, 1H), 5.01-4.74 (m, 1H), 3.81-3.58 (m, 2H), 3.48-3.34 (m, 1H), 3.10-2.96 (m, 1H), 2.42 (d, J=12.8 Hz, 1H), 2.28 (s, 3H), 1.60-1.46 (m, 2H), 1.37 (d, J=19.1 Hz, 9H), 0.96-0.75 (m, 3H). MS (ES+) m/z: 455.2 (M+H); LC retention time: 3.038 min (analytical HPLC Method O).

Provenance & Evidence