Ammonium Chloride → 3-amino-5-cyano-6-ethoxy-N-((1-((2-(pyridin-2-yl)thiazol-5-yl)methyl)piperidin-4-yl)methyl)picolinamide

Participants

Reaction Steps

To a stirred solution of the compound prepared in Example 448 (48 mg) in tetrahydrofuran (1 mL) at ambient temperature was added zinc dust (120 mg), and to the resulting stirred mixture added saturated ammonium chloride (0.5 mL). The resulting mixture was stirred at ambient temperature for 17 hours. The reaction mixture was diluted with tetrahydrofuran (5 mL) and filtered through a glass microfibre filter. The flask and filter were rinsed with additional tetrahydrofuran. The combined filtrate and rinses were concentrated to remove most of the tetrahydrofuran, and the residue was partitioned between ethyl acetate and water, with addition of 10% sodium carbonate. The organic layer was dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel, eluting with 99/1 chloroform/methanol to provide the title compound (20 mg) with the following physical data. 1H NMR (CDCl3): δ 8.60 (d, J=4.4 Hz, 1H), 8.15 (d, J=8.0 Hz, 1H), 7.79 (m, 2H), 7.68 (s, 1H), 7.32 (m, 2H), 5.77 (broad s, 2H), 4.35 (q, J=7.2 Hz, 2H), 3.80 (broad s, 2H), 3.33 (t, J=6.8 Hz, 2H), 2.99 (d, J=10.8 Hz, 2H), 2.11 (t, J=10.8 Hz, 2H), 1.76 (d, J=12.0 Hz, 2H), 1.60 (broad s, 1H), 1.41 (m, 5H);

Provenance & Evidence