1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 68689712, compound

Participants

Reaction Steps

N-{4-[(3S)-3-Aminopyrrolidin-1-yl]phenyl}-5-fluoro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidin-2-amine (Example 153; 220 mg, 0.556 mmol), L—lactic acid (61 mg, 0.667 mmol), HOBt mono hydrate (103 mg, 0.667 mmol) and Hunig's base (0.12 ml, 0.667 mmol) in DCM (5 ml) were reacted with EDAC (128 mg, 0.667 mmol) at room temperature under nitrogen for 18 hours. The mixture was diluted with DCM (20 ml) and washed with water (20 ml), 1 N aqueous potassium hydroxide (20 ml) and saturated aqueous sodium chloride (15 ml). The mixture was dried and after evaporation under reduced pressure purified by HPLC on a Phenomenex column, (0-50% acetonitrile/water, 0.2% TFA). The fractions were diluted with water (20 ml), basified with solid potassium carbonate, and extracted twice with EtOAc/DCM (20 ml, 2:1). The solution was washed with saturated aqueous sodium chloride (15 ml), dried and after evaporation under reduced pressure gave the title compound as a yellow solid, (79 mg, 30%). NMR: 1.20 (d, 3H), 1.37 (d, 6H), 1.90-2.04 (m, 1H), 2.11-2.27 (m, 1H), 2.47 (s, 3H), 3.00-3.09 (m, 1H), 3.20-3.47 (m, 3H), 3.91-4.00 (m, 1H), 4.32-4.47 (m, 1H), 5.38 (s, 1H), 5.40-5.49 (m, 1H), 6.49 (d, 2H), 7.30 (s, 1H), 7.32 (d, 2H), 7.76 (d, 1H), 8.40 (d, 1H), 9.06 (s, 1H); m/z 468.

Provenance & Evidence