6-Fluoropyridin-2-amine → HCID 68688006, compound

Participants

Reaction Conditions

Reaction Steps

Part C′: When the procedures described above were employed utilizing 2-amino-6-fluoropyridine as the commercial starting material the isolated crude product of part C was 3.90 g of a mixture of tert-butyl 4-(1-(6-fluoropyridin-2-yl)-1H-tetrazol-5-yl)piperazine-1-carboxylate and tert-butyl 4-(1-(6-azidopyridin-2-yl)-1H-tetrazol-5-yl)piperazine-1-carboxylate. This crude product was dissolved in a mixture of 120 mL of methanol and 20 mL of water. To this solution at 25° C. was added in portions 1.60 g of sodium borohydride, and the mixture was stirred at 25° C. for 4 h. The reaction mixture then was concentrated under vacuum, and the residue was diluted with water and ethyl acetate. The phases were separated, and the organic phase was washed with water (×2) and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography on silica gel (elution: 0-100% diethyl ether/methylene chloride) afforded tert-butyl 4-(1-(6-fluoropyridin-2-yl)-1H-tetrazol-5-yl)piperazine-1-carboxylate (3.26 g) [Mass Spec.: m/e: 350.32 (M+H)+ [calc'd: 350.17]; 1H NMR (300 MHz, CDCl3) δ 8.05 (m, 1H), 7.78 (m, 1H), 7.05 (m, 1H), 3.60 (m, 4H), 3.40 (m, 4H), 1.46 (s, 9H)] and tert-butyl 4-(1-(6-aminopyridin-2-yl)-1H-tetrazol-5-yl)piperazine-1-carboxylate (0.28 g) [Mass Spec.: m/e: 347.37 (M+H)+ [calc'd: 347.19]; 1H NMR (300 MHz, DMSO-D6) δ 7.64 (t, 1H, J=8 Hz), 6.79 (d, 1H, J=8 Hz), 6.60 (d, 1H, J=8 Hz), 6.55 (br s, 2H), 3.40 (m, 4H), 3.24 (m, 4H), 1.41 (s, 9H)].

Provenance & Evidence