Hydrochloric Acid → HCID 89463057, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2-(1-benzyl-6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-((tetrahydro-2H-pyran-2-yl)oxy)acetonitrile (1.8 g, 3.09 mmol) in Ethanol (50 mL) was treated with NaOH (25 mL, 144 mmol) and the mixture was heated at 140° C. in a sealed tube overnight. HCl (conc.) was added until pH<2 and then the mixture was extracted with ethyl acetate. The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. The resulting residue was dissolved in Methanol (30 mL), cooled to 0° C. and then treated with TMS-diazomethane (6.19 mL, 12.38 mmol). The mixture was stirred for 2 hours and then concentrated. The resulting residue was dissolved in t-Butyl acetate (10 mL), treated with perchloric acid (0.186 mL, 3.09 mmol) and then stirred at ambient temperature overnight. The mixture was diluted with ethyl acetate, washed with 1M NaOH, then brine. The organic phase was then dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel (0-70% ethyl acetate/hexanes) to afford the title compound (280 mg) as well as 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-hydroxyacetate (500 mg). An ice cold 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-hydroxyacetate (500 mg) in t-Butyl acetate (5 mL) was treated with perchloric acid (1 eq.) then kept at 0° C. for 2 days without stirring. The mixture was diluted with ethyl acetate, washed with 1M NaOH, then brine. The organic phase was then dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel (0-70% ethyl acetate/hexanes) to afford the title compound (290 mg). The material from each purification was combined to give the title compound (570 mg, 34% yield). 1H NMR (400 MHz, CHLOROFORM-d) ppm 7.37-7.29 (m, 5H), 7.15 (m, 1H), 7.02-6.91 (m, 1H), 6.74 (m, 1H), 5.99-5.67 (m, 3H), 5.28 (s, 0.7H), 5.10 (s, 0.3H), 4.27-4.15 (m, 2H), 3.77 (s, 2H), 3.73 (s, 1H), 3.67 (s, 3H), 2.77-2.58 (m, 2H), 2.17-2.03 (m, 2H), 1.92 (s, 3H), 1.12 (s, 3H), 0.97 (s, 6H); LC/MS (m/z) ES+=529 (M+1).

Provenance & Evidence