Diisopropylethylamine → HCID 68291496, compound

Temperature

80 °C

To a solution of 6-bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (Intermediate 2, 0.27 g, 0.99 mmol) in DMF (1 mL) was added (±)-cis-benzyl 3-amino-4-methoxypyrrolidine-1-carboxylate (Intermediate 12, 0.3 g, 1.18 mmol) and DIPEA (0.37 mL, 2.1 mmol). The mixture was heated at 80° C. overnight. The mixture was then poured into water, stirred for 1 h, and filtered. The solid was rinsed with water, dried under vacuum. The solid was dissolved in acetonitrile (5 mL) and iodotrimethylsilane (0.590 g, 2.95 mmol) was added at 0° C., then the mixture was stirred at rt for 3 h, diluted with ether and stirred at rt for 1 h. The solids were filtered and rinsed with ether and dried to afford the hydroiodide salt of 6-bromo-4-((cis-4-methoxypyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (0.4 g, 84% yield) as brown solid. 1H NMR (400 MHz, METHANOL-d4) δ 8.17 (s, 1H), 7.70 (d, J=1.5 Hz, 1H), 7.07 (s, 1H), 4.97-4.88 (m, 2H), 4.56 (br. s., 1H), 4.16-4.09 (m, 1H), 3.67 (dd, J=11.4, 7.7 Hz, 1H), 3.53-3.50 (m, 3H), 3.50-3.45 (m, 1H), 3.40-3.34 (m, 1H), 3.11 (dd, J=11.6, 8.5 Hz, 1H); MS (ES+) m/z: 353.1, 354.0 (M+H); LC retention time: 2.01 min (analytical HPLC Method J).

1. filtrationfiltered
2. washThe solid was rinsed with water
3. customdried under vacuum
4. dissolutionThe solid was dissolved in acetonitrile (5 mL)
5. stirringthe mixture was stirred at rt for 3 h
6. stirringstirred at rt for 1 h
7. filtrationThe solids were filtered
8. washrinsed with ether
9. customdried

ORD record

ord-e75787f5c2ac4b9c9b20c9bba36eedb4

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987268B2