Hydrochloric Acid → HCID 86706106, compound

Participants

Reaction Steps

A solution of ((S)-2-{(S)-3-[(R)-1-(7-bromo-quinolin-2-yl)-ethylcarbamoyl]-tetrahydro-pyridazin-1-yl}-1-methyl-2-oxo-ethyl)-carbamic acid tert-butyl ester (838 mg, 1.44 mmol) in dichloromethane (20 mL) was treated with hydrogen chloride in 1,4-dioxane (4 M, 1.44 mL, 5.76 mmol) and stirred for 2 h at room temperature. The solution was evaporated to dryness. The residue was dissolved in dichloromethane (20 mL) and (2S,3S)-2-hydroxy-3-methoxy-butyric acid (193 mg, 1.44 mmol) was added followed by N,N-diisopropylethylamine (1.0 mL, 5.76 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (819 mg, 2.16 mmol). The solution was stirred at room temperature for 20 h and then evaporated to dryness. The residue was purified by silica gel chromatography eluting with a gradient of acetone/ethyl acetate 1:9 to 1:1 to yield the title compound (243 mg, 31%) as a white gum. 1H NMR (300 MHz, CDCl3) δ 1.14 (d, J=6.2 Hz, 3H), 1.33-1.50 (m, 6H), 1.58 (d, J=6.7 Hz, 3H), 2.20-2.30 (m, 1H), 2.66-2.79 (m, 1H), 3.26-3.63 (m, 3H), 3.37 (s, 3H), 3.90 (d, J=11.8 Hz, 1H), 4.20 (d, J=5.1 Hz, 1H), 4.46-4.56 (m, 1H), 5.20-5.31 (m, 1H), 5.36-5.49 (m, 1H), 7.41 (d, J=8.5 Hz, 1H), 7.61-7.70 (m, 2H), 8.15 (d, J=8.5 Hz, 1H), 8.41 (s, 1H). LCMS (m/z) 550.0, 552.0 [M+H], Tr=2.05 min.

Provenance & Evidence