Dichloromethane → [[2-(methylthio)-6-ethyl-7-([1,1'-biphenyl]-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester

Participants

Reaction Steps

To a suspension of 64 mg (2.66 mmol) of sodium hydride in 5 mL of benzene was added 200 mg (2.22 mmol) of methyl glycolate and a solution of 350 mg (0.89 mmol) of 2-(methylthio)-4-chloro-6-ethyl-7-([1,1′-biphenyl]-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidine in 2.5 ml of benzene then the mixture heated to 60° C. The reaction was monitored for conversion to product by TLC (silica, methylene chloride). Additional sodium hydride (96 mg) and methyl glycolate (360 mg) were added in portions over 4 days. The reaction was cooled to ambient temperature and partitioned by the addition of 15 mL of 2 M sodium hydrogen sulfate and 15 mL of ethyl acetate. The aqueous phase was extracted twice with 7 mL portions of ethyl acetate. The combined organic phases were dried with sodium sulfate and concentrated. The product was purified by flash chromatography (53 g silica, hexanes-ethyl acetate gradient 100:0 to 85:15) to provide 187 mg (47%) of [[2-(methylthio)-6-ethyl-7-([1,1′-biphenyl]-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester as a solid. nmr (300 MHz, CDCl3) δ1.10 (t, 3H), 2.16 (q, 2H), 2.52 (s, 3H), 3.80 (s, 3H), 5.03 (s, 2H), 5.32 (s, 2H), 6.25 (s, 1H), 6.62 (d, 1H), 7.1-7.6 (m, 8H)

Provenance & Evidence