反应详情

A 2 M aqueous solution of sodium hydroxide (6 mL, 12.00 mmol) was added to a solution of (R)-ethyl 4-((1-(tert-butoxycarbonyl)-3,3-dimethylpiperidin-4-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylate (1.187 g, 2.58 mmol) in methanol (11 mL) and tetrahydrofuran (11 mL) at room temperature. The resulting mixture was heated at reflux for 40 min and cooled to room temperature. The organic solvents were evaporated in vacuo. The residue was neutralized to pH 5 with 1 N HCl. The resulting precipitate was collected by filtration to give (R)-4-((1-(tert-butoxycarbonyl)-3,3-dimethylpiperidin-4-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylic acid as brown solid (1.13 g, 97% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.57 (br. s., 1H), 11.16 (d, J=8.8 Hz, 1H), 8.31 (s, 1H), 8.05 (d, J=1.3 Hz, 1H), 7.23 (s, 1H), 4.12-4.00 (m, 1H), 3.87 (br. s., 1H), 3.56 (d, J=12.8 Hz, 1H), 3.01 (br. s., 2H), 1.91 (dd, J=13.5, 3.2 Hz, 1H), 1.56 (d, J=8.1 Hz, 1H), 1.41 (s, 9H), 0.98 (s, 3H), 0.92 (s, 3H); MS (ES+) m/z: 432.2 (M+H); LC retention time: 3.795 min (analytical HPLC Method H).

1. temperatureThe resulting mixture was heated
2. temperatureat reflux for 40 min
3. customThe organic solvents were evaporated in vacuo
4. filtrationThe resulting precipitate was collected by filtration