[[2-(methylthio)-6-ethyl-7-([1,1'-biphenyl]-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester → [[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 85 mg (3.55 mmol) of sodium hydride in 4 mL of benzene was added 326 mg (3.55 mmol) of methyl glycolate and a solution of 200 mg (0.507 mmol) of 2-(methylthio)-4-chloro-6-ethyl-7-([1,1′-biphenyl]-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidine in 8 ml of benzene. The mixture was heated at 60° C. and monitored by TLC (silica, methylene chloride) for conversion to product. After 70 hours, 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 to provide 380 mg of yellow oil containing [[2-(methylthio)-6-ethyl-7-([1,1′-biphenyl]-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester as the major component. The crude oil was dissolved in 30 mL of ethanol, treated with 2.28 g of Raney Ni, then the mixture heated to reflux. After 18 hours, the solids were removed by filtration through a filter aid and the reaction concentrated to an oil. The oil was purified by flash chromatography ( 46 g silica, hexanes-ethyl acetate gradient 100:0 to 2:1) to provide 203 mg (quantitative yield for 2 steps) of [[6-ethyl-7-([1,1′-biphenyl]-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester as an oil. nmr (300 MHz, CDCl3) δ1.14 (t, J=7.5 Hz, 3H), 2.32 (q, J=7.5 Hz, 2H), 3.79 (s, 3H), 5.08 (s, 2H), 5.38 (s, 2H), 6.37 (s, 1H), 6.5 (d, J=7.1 Hz, 1H), 7.1-7.6 (m, 8H), 8.37 (s, 1H)

Provenance & Evidence