Ammonia → HCID 25129212, compound

Participants

Reaction Steps

To a stirred solution of the product of Example 435 (217 mg, 0.4 mmol) in DMF (10 mL) was added HATU (169 mg, 0.4 mmol), Hunig's base (0.1 ml, 0.4 mmol) and NH3 (0.5 M in dioxane) (2.2 mL, 0.7 mmol). The resulting solution was stirred at rt overnight, diluted with H2O, and extracted with EtOAc(3×50 mL). The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give an oil which was purified by flash chromatography (0-7% MeOH/CH2Cl2) to give the title compound as a racemic mixture. The racemic mixture was separated by HPLC on a chiralcel OD column with 20% MeOH/CO2 as the mobile phase. The faster eluting enantiomer (E1) has a retention time of 4.0 minutes, while the slower enantiomer (E2) has a retention time of 4.6 minutes. E1: 1H NMR (500 MHz, (CD3)2CO): δ 8.11 (s, 1H), 7.73 (d, J=7.5 Hz, 1H), 7.31-7.35 (m, 3H), 7.28 (dd, J=1.5, 7.5 Hz, 1H), 7.18 (dd, J=1.5, 7.5 Hz, 1H), 7.13 (d, J=7.5 Hz, 1H), 7.09 (d, J=7.5 Hz, 2H), 6.55 (s, 1H), 6.31 (s, 1H), 5.11 (d, J=17.5 Hz, 1H), 4.81 (d, J=17.5 Hz, 1H), 1.85 (s, 3H), 1.74 (s, 3H). LCMS: m/e 587.08 (M+H)+.

Provenance & Evidence