Sodium Bicarbonate → Ethyl 1-(1-methylazetidin-3-yl)-4-oxo-6-(6-(3-propylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1,4-dihydroquinoline-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

A suspension of ethyl 6-iodo-1-(1-methylazetidin-3-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (Intermediate 31, 500 mg, 1.21 mmol) in dimethoxyethane (9.7 mL) in a vial was stirred with heating to obtain solution. The solution was cooled to 30° C. and trans dichlorobis(triphenylphosphine)palladium (II) (111 mg, 0.16 mmol) was added. The mixture was stirred for ˜10 min at room temperature, then 6-(3-propylureido)-4-(4-trifluoromethylthiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 47, 1.3 eq) was added to the mixture followed by an aqueous solution of sodium bicarbonate (252 mg in 2.4 mL of water) and the vial was sealed. The mixture was stirred at 75° C. for 1 h and then cooled to 0° C. The solid that formed was isolated by filtration, washed with a small amount of dimethoxyethane, then methyl tert-butyl ether to give 735 mg of yellow solid, which was used without further purification.

Provenance & Evidence