Ammonium Chloride → tert-butyl ((1S,4S)-4-(2-cyclopropyl-2-hydroxyethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamate

Participants

Reaction Steps

To a solution of cyclopropyl magnesium bromide (6.88 mL of a 0.5 M solution in THF, 3.44 mmol, 8 eq) in THF (5 mL) at 0° C. under Ar was added a solution of the product of Step A (195 mg, 0.43 mmol, 1 eq) in THF (17 mL) dropwise over 30 min. After 45 min, saturated NH4Cl was added, the solution extracted with ethyl acetate, the organics combined, dried over MgSO4 and concentrated. Purification by chromatography (12 g column) eluting with 30 to 100% EtOAc/heptane afforded the title compound of Step B as a mix of diastereomers. 1H NMR (CHLOROFORM-d) δ: 8.70 (br. s., 1H), 7.70 (br. s., 1H), 6.11-6.42 (m, 1H), 5.77 (t, J=5.1 Hz, 1H), 4.81 (d, J=12.2 Hz, 4H), 4.03 (dt, J=12.8, 6.2 Hz, 1H), 3.81-3.98 (m, 1H), 3.59-3.75 (m, 2H), 3.03-3.25 (m, 2H), 2.69-3.00 (m, 2H), 2.19-2.67 (m, 3H), 1.91-2.18 (m, 3H), 1.55-1.88 (m, 5H), 1.42 (s, 9H), 0.88-0.99 (m, 1H), 0.42-0.56 (m, 2H), 0.14-0.35 (m, 2H). Calculated for C25H32F3N3O4: 496.2 (M+1). found: 496.2.

Provenance & Evidence