Dimethylformamide → 2-Amino-1-ethyl-7-(3-methyl-3-trimethylsilanyloxybut-1-yn-1-yl)-N-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

In a 2 l three-necked flask, 40.7 g of 2-amino-7-chloro-1-ethyl-N-methyl-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxamide (0.145 mole) and 56.2 ml of [(1,1-dimethyl-2-propynyl)oxy]trimethylsilane (0.290 mol) are successively introduced into a mixture of 365 ml of dimethylformamide and 365 ml of triethylamine. The reaction mixture is sparged with argon for 15 minutes and then 0.983 g of CuI (5.16 mmol) and 5.1 g of bis(triphenylphosphine) palladium(II)dichloride (7.2 mmol) are added successively. The reaction mixture is heated for 15 hours at 90° C. and then concentrated under a reduced vacuum. The residue is taken up in 500 ml of an ethyl acetate/NaHCO3aq mixture (V/V=1/1) and filtered over a celite buffer, rinsing being carried out with ethyl acetate. The aqueous phase is extracted with dichloromethane (3×50 ml) and the organic phases are then combined, dried over sodium sulphate, filtered, and concentrated under vacuum. The reaction crude is purified by silica column chromatography (elution with a dichloromethane:ethyl acetate gradient, 80:20 to 50:50, and then a dichloromethane:methanol gradient, 95:5 to 90:10) so as to give 36.2 g of expected product (yield=62.3%) and also 7.4 g of desilylated product described in the next step (yield=15.5%).

Provenance & Evidence