Diisopropylethylamine → 2-[4-(benzotriazol-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 3-cyclopentyl-2-(4-iodo-6-oxo-6H-pyridazin-1-yl)-propionic acid (Intermediate 85, 1.44 g, 3.98 mmol) in N,N-dimethylformamide (18 mL, 0.22M) at 25° C. was treated with N,N-diisopropylethylamine (2.0 mL, 12.10 mmol), (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (2.64 g, 5.97 mmol) and 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-ylamine (Intermediate 4, 0.88 g, 4.46 mmol). The reaction was stirred at 25° C. over 3 nights. After this time, the reaction was diluted with ethyl acetate (150 mL) and was washed with a saturated aqueous ammonium chloride solution (150 mL), a saturated aqueous sodium bicarbonate solution (150 mL) and a saturated aqueous sodium chloride solution (150 mL), dried over magnesium sulfate, filtered, rinsed and concentrated in vacuo. Silica gel column chromatography (AnaLogix 80 g, 25-75% gradient ethyl acetate/hexanes) afforded 2-[4-(benzotriazol-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide (1.11 g, 51%) as an off-white solid as a mixture of diastereomers.

Provenance & Evidence