Cesium carbonate → methyl 2-(tert-butoxy)-2-(6-methyl-1-(4-(methylsulfonyl)benzyl)-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate

Participants

Reaction Conditions

Reaction Steps

A suspension of methyl 2-(tert-butoxy)-2-(6-methyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (17 mg, 0.044 mmol) in Acetonitrile (0.4 mL) was treated with Cs2CO3 (57.9 mg, 0.178 mmol), 4-methylsulfonylbenzyl bromide (44.3 mg, 0.089 mmol), and stirred at 70° C. for 1.5 hours. The reaction was cooled to rt, diluted with water and 1N HCl, extracted with EtOAc, washed with Brine, dried with Na2SO4, filtered, and concentrated. Purification with column chromatography (0-100% EtOAc/Hexane) gave methyl 2-(tert-butoxy)-2-(6-methyl-1-(4-(methylsulfonyl)benzyl)-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (22 mg, 0.040 mmol, 90% yield) as yellow oil. The ester intermediate was dissolved in Methanol (0.5 mL) and Tetrahydrofuran (THF) (0.5 mL), treated with 2M LiOH (0.120 mL, 0.24 mmol), and stirred at 60° C. for 2 hours. The reaction was concentrated and purified with reverse phase HPLC (20-100% MeCN/H2O-0.1% TFA) to give title compound (9.3 mg, 0.017 mmol, 37.6 yield) as off white solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 1.00 (s, 9H), 2.44 (s, 3H), 3.02 (s, 3H), 3.64 (s, 3H), 5.47 (s, 1H), 5.81 (d, J=15.7 Hz, 1H), 6.02 (d, J=15.6 Hz, 1H), 6.10 (d, J=2.8 Hz, 1H), 7.05 (d, J=2.9 Hz, 1H), 7.29 (d, J=8.1 Hz, 2H), 7.32-7.43 (m, 3H), 7.47-7.58 (m, 1H), 7.89 (d, J=8.4 Hz, 2H). LCMS (m/z) ES+=537 (M+1).

Provenance & Evidence