Sodium Bicarbonate → (R)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-4-oxo-1-(pyrrolidin-3-ylmethyl)-1,4-dihydroquinoline-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

A vial was charged with (R)-ethyl 6-iodo-4-oxo-1-(pyrrolidin-3-ylmethyl)-1,4-dihydroquinoline-3-carboxylate hydrochloride (Intermediate 97, 1.0 g, 2.16 mmol), 6-(3-ethylureido)-4-(4-trifluoromethylthiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 17, 940 mg, 2.61 mmol), and sodium bicarbonate (730 mg, 8.65 mmol) in dimethoxyethane (10 mL) and water (2 mL). The reaction mixture was purged with N2 for about 5 min, then trans-dichlorobis(triphenylphosphine)palladium (II) (160 mg, 0.228 mmol) was added. The reaction mixture was heated for 3 h at 80-85° C., then cooled to room temperature and water (10 mL) was added. The precipitated solid was collected by filtration to give (R)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-4-oxo-1-(pyrrolidin-3-ylmethyl)-1,4-dihydroquinoline-3-carboxylate (1.1 g, 82.7%) as a light brown solid after drying under vacuum at 40° C. overnight.

Provenance & Evidence