4-Methylmorpholine → 1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Participants

Reaction Steps

Ethyl 1-(1-methylethyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate (270 mg, 0.873 mmol) was suspended in THF (1913 μl) and Methanol (6378 μl). To the mixture was added 3N NaOH (436 μl, 1.309 mmol) and the contents heated on an aluminum block at 55° C. overnight. The solvent was removed in vacuo. The remaining orange residue was dissolved with water (10 mL) and cooled with stirring in an ice bath. The contents were acidified by dropwise addition 1N HCl until precipitation ceased. The white solid was collected via vacuum filtration and the filter cake was dried open to the air, under vacuum overnight. The white solid was added to a 20 mL vial followed by 3-(aminomethyl)-6-methyl-4-propyl-2(1H)-pyridinone (208 mg, 0.960 mmol), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (251 mg, 1.309 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol hydrate (202 mg, 1.309 mmol) and DMSO (4 ml). To the same was added a magnetic stir bar and 4-methylmorpholine (618 mg, 6.11 mmol). The reaction was stirred at room temperature overnight. The reaction contents were slowly poured onto an aqueous solution of sat Na2CO3 (6 mL) and water (20 mL) and stirred in an ice bath. The resulting suspension was stirred 20 minutes. The solid was collected by vacuum filtration and dried under high vacuum overnight. The title compound was obtained as an off-white solid (388 mg, 99%). 1H NMR (400 MHz, DMSO-δ6) δ 9.00 (t, J=3.92 Hz, 1H), 8.38 (s, 1H), 8.23-8.29 (m, 2H), 8.16 (s, 1H), 7.46-7.62 (m, 3H), 5.93 (s, 1H), 5.34 (quin, J=6.63 Hz, 1H), 4.45 (d, J=4.55 Hz, 2H), 2.55 (s, 2H), 2.14 (s, 3H), 1.56 (d, J=6.57 Hz, 6H), 1.45-1.54 (m, 2H), 0.88 (t, J=7.20 Hz, 3H). LCMS(ES) [M+H]+ 444.3.

Provenance & Evidence