Ammonia → (s,s)-n-{1-[3-Carbamoyl-1-(5-fluoro-2,3-dihydro-indol-1-ylmethyl)-propylcarbamoyl]-3-methyl-butyl}-3-methyl-benzamide

Participants

Reaction Steps

The title compound of Example 43 (30 mg, 61 μmol) was treated with dioxane (2 mL) and concentrated ammonia (0.2 mL). HATU (35 mg, 92 μmol) was added and the reaction was stirred overnight. Another portion of HATU (80 mg, 210 μmol) was added and the reaction was stirred for an additional 3 hours. The reaction was then diluted with ethyl acetate and extracted once with 1 M NaOH solution. The organics were dried over MgSO4 and the solvent was removed. The residue was purified by silica gel column chromatography using DCM and methanol as solvents to afford the title compound (25 mg, 84%); 1H NMR (CDCl3, 400 MHz) δ 0.90 (s, 3H), 0.91 (s, 3H), 0.88-0.99 (m, 1H), 1.58-1.80 (m, 4H), 1.97-2.12 (m, 2H), 2.23-2.30 (m, 2H), 2.37 (s, 3H), 2.82 (s, 2H), 2.85-3.04 (m, 3H), 3.15 (dd, 1H, J1=6.5, J2=13.6), 3.34 (dd, 1H, J1=8.4, J2=16.9), 3.48 (dd, 1H, J1=8.1, J2=16.0), 4.12-4.21 (m, 1H), 4.40-4.72 (m, 1H), 5.86 (s, 1H), 6.32-6.47 (m, 2H), 6.72 (dd, 1H, J1=J2=8.4), 6.79 (d, 1H, J=7.4), 6.94 (d, 1H, J=7.6), 7.06 (d, 1H, J=8.4), 7.23-7.36 (m, 2H), 7.52-7.61 (m, 2H); HPLC-MS calcd. for C27H35FN4O3 (M+H+) 483.3, found 483.5.

Provenance & Evidence