Hydrochloric Acid → HCID 71537059, compound

Participants

Reaction Conditions

Reaction Steps

A solution of methyl 2-(1-benzyl-6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-(tert-butoxy)acetate (40 mg, 0.076 mmol) in Tetrahydrofuran (THF) (0.2 mL), Methanol (0.200 mL), Water (0.200 mL) was treated with NaOH (24.21 mg, 0.605 mmol) and heated at 70° C. for 3 hours. The mixture was cooled to 0° C., treated with HCl (1M) until pH <2 and then extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The resultant was dissolved in Tetrahydrofuran (THF) (0.2 mL), treated with KHMDS (0.757 mL, 0.378 mmol) and stirred at ambient temperature for one hour. Additional KHMDS (0.757 mL, 0.378 mmol) was added and the mixture was heated to 70° C. for 2 hours. The mixture was cooled to 0° C., treated with HCl (1M) until pH <2 and then extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The resultant was dissolved in N,N-Dimethylformamide (DMF) (0.5 mL), treated with MeI (0.024 mL, 0.378 mmol) and potassium carbonate (52.3 mg, 0.378 mmol) and then stirred at ambient temperature overnight. Water was added and the mixture was extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The resultant was dissolved in Tetrahydrofuran (THF) (0.2 mL), Methanol (0.200 mL) and Water (0.200 mL), treated with NaOH (24.21 mg, 0.605 mmol) and then heated to 70° C. for 3 hours. The mixture was cooled to 0° C., treated with HCl (1 M) until pH <2 and then extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min) to afford 2-(tert-butoxy)-2-(1,6-dimethyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetic acid (6 mg, 0.013 mmol, 17.72% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 7.28-7.33 (m, 1H) 6.96-7.02 (m, 1H) 6.92-6.96 (m, 1H) 6.70-6.81 (m, 1H) 5.70-5.81 (m, 1H) 5.15-5.46 (m, 1H) 4.17-4.25 (m, 5H) 3.66-3.68 (m, 3H) 2.60-2.77 (m, 2H) 2.06-2.16 (m, 2H) 1.92-2.05 (m, 3H) 0.98-1.05 (m, 9H); LCMS (m/z) ES+=439 (M+1).

Provenance & Evidence