Oxalyl chloride → 2-[2-(3-chlorophenyl)-ethoxymethyl]-6-fluoro-3H-pyrido[2,3-d]pyrimidin-4-one

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Reaction Steps

To a solution of 2,5-difluoropyridine-3-carboxylic acid (150 mg, 0.94 mmol) in CH2Cl2 (5 ml) at 0° C. was added oxalylchloride (97 μl, 1.13 mmol) dropwise followed by 2 drops of DMF. The reaction mixture was warmed to room temperature and stirred for 4 h. The reaction mixture was concentrated in vacuo and used in the next step without further purification. The crude acid chloride was dissolved in MeCN (5 ml) and N,N-diisopropyl ethyl amine (345 μl, 2.67 mmol) was added followed by 2-[2-(3-chlorophenyl)-ethoxy]-acetamidine hydrochloride salt (222 mg, 0.89 mmol) (prepared as described in example 79.2). The reaction mixture was stirred at room temperature for 16 h and then heated to reflux for an additional 16 h. The reaction mixture was cooled to room temperature and concentrated in vacuo to give a residue which was partitioned between water and ethyl acetate. The organic phases were combined, washed with 1N HCl, sat. NaHCO3, brine, dried over MgSO4, filtered and concentrated in vacuo to give a crude residue which was triturated with ether (3×5 ml) to give the desired product 2-[2-(3-chlorophenyl)-ethoxymethyl]-6-fluoro-3H-pyrido[2,3-d]pyrimidin-4-one (65 mg, 0.19 mmol; 22%) as an off white solid. MS: m/e=334.1 [M+H+].

Provenance & Evidence