Diisopropylethylamine → ethyl 4-(((3S,4S)-1-((benzyloxy)carbonyl)-4-methylpyrrolidin-3-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of ethyl 3-carbamoyl-4-chloropyrrolo[1,2-b]pyridazine-6-carboxylate (Intermediate 1, 375 mg, 1.401 mmol), (3S,4S)-benzyl 3-amino-4-methylpyrrolidine-1-carboxylate (Intermediate 5, 361 mg, 1.541 mmol) and diisopropylethylamine (0.734 mL, 4.20 mmol) in DMA (5 mL) was heated to 100° C. for 3 hr. After cooling, the volatiles were removed in vacuo and the residue was triturated with water. Filtration and drying afforded a tan solid that was rinsed with hexane and redried to afford ethyl 4-(((3S,4S)-1-((benzyloxy)carbonyl)-4-methylpyrrolidin-3-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylate (650 mg, 1.396 mmol, 100% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ 11.29 (d, J=7.3 Hz, 1H), 8.34 (s, 1H), 8.13 (d, J=2.4 Hz, 1H), 7.50-7.06 (m, 7H), 5.15-4.96 (m, 2H), 4.81 (d, J=4.8 Hz, 1H), 4.35-4.20 (m, 2H), 3.85-3.63 (m, 2H), 3.45 (dd, J=10.9, 3.4 Hz, 1H), 3.09 (dt, J=16.1, 10.2 Hz, 1H), 2.72-2.58 (m, 1H), 1.34-1.27 (m, 3H), 1.07 (d, J=6.8 Hz, 3H). MS (ES+) m/z: 466.3 (M+H); LC retention time: 3.095 min (analytical HPLC Method O).

Provenance & Evidence