Sodium Bicarbonate → tert-butyl 2-(6-amino-5-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-3-yl)-4,5-dihydrothieno[2,3-c]pyridine-6(7H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (250 mg, 0.63 mmol), tert-butyl 2-bromo-4,5-dihydrothieno[2,3-c]pyridine-6(7H)-carboxylate (198 mg, 0.63 mmol), and NaHCO3 (1.56 mL, saturated solution in H2O) in N,N-dimethylformamide (8.3 mL) was degassed with a nitrogen stream for 20 min. To this mixture was added [1,1′-bis(diphenylphosphino)-ferrocene]palladium (II) dichloride (46 mg, 0.06 mmol) and the reaction was stirred in a microwave for 10 min at 120° C. The resulting crude mixture was diluted with ethyl acetate (30 mL) and filtered. The filtrate was washed with H2O (2×15 mL) and brine (1×15 mL), concentrated under reduced pressure, and purified via silica gel chromatography to provide tert-butyl 2-(6-amino-5-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-3-yl)-4,5-dihydrothieno[2,3-c]pyridine-6(7H)-carboxylate. This material (137 mg, 0.27 mmol) was treated with HCl (4 mL, 4.0 N in dioxane) for 1 hr, and solvent was removed under reduced pressure. The residue was dissolved in MeOH (500 mL) and treated with cold diethyl ether (˜15 mL). The resulting precipitate was collected and dried in vacuo to provide the hydrochloride salt of 3-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl)pyridin-2-amine as a bright yellow solid (103 mg, 37% yield over two steps); 1H NMR (DMSO-d6): 9.50 (s, 2H), 8.44 (d, J=2.4 Hz, 1H), 7.85-7.46 (m, 4H), 7.05 (s, 1H), 4.29 (s, 2H), 3.39-3.25 (m, 2H), 2.85-2.81 (m, 2H); ES-MS: m/e=412.2 (M+H).

Provenance & Evidence