Hydrochloric Acid → 2-[1-Benzyl-4-(4-chlorophenyl)-3,6-dimethyl-7-oxo-pyrrolo[2,3-c]pyridin-5-yl]-2-tert-butoxy-acetic acid

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Reaction Steps

A mixture of the methyl 2-(1-benzyl-3-bromo-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-(tert-butoxy)acetate (15 mg, 0.026 mmol), trimethylboroxine (3.65 μL, 0.026 mmol) and Na2CO3 (5.56 mg, 0.052 mmol) in N,N-Dimethylformamide (DMF) (1 mL), was degassed with N2 for 5 minutes. Palladium tetrakis (3.03 mg, 2.62 μmol) was added and the mixture was degassed again with N2 for 5 minutes. The mixture was irradiated in the microwave at 140° C. for 30 minutes. The mixture was diluted with Methanol (1.000 mL), and Tetrahydrofuran (THF) (1.000 mL), treated with 2M LiOH (1 mL, 2.000 mmol) and then stirred at room temperature overnight. The mixture was treated with HCl (1M) until pH<2 and extracted with ethyl acetate. The combined extracts were concentrated and purified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min) to afford 2-(1-benzyl-4-(4-chlorophenyl)-3,6-dimethyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-(tert-butoxy)acetic acid (4.0 mg, 0.007 mmol, 30% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 7.63-7.57 (m, 1H), 7.49-7.41 (m, 2H), 7.38-7.29 (m, 6H), 6.81 (s, 1H), 5.81 (s, 2H), 5.18 (s, 1H), 3.67 (s, 3H), 1.44 (s, 3H), 1.07 (s, 9H); LCMS (m/z) ES+=493 (M+1).

Provenance & Evidence