Methanol → 3-(hydroxymethyl)pyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-6(5H)-one

Participants

Reaction Conditions

Reaction Steps

To a suspension of methyl 6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidine-3-carboxylate (0.62 g, 2.55 mmol) in THF (Volume: 15 mL) was added Sodium hydride (0.092 g, 3.82 mmol) at 0° C. The reaction was stirred at 0° C. for 15 min. The suspension was cooled to −78° C. and Lithium aluminum hydride solution (2.294 mL, 4.59 mmol) was added during 10 min. The reaction was stirred at −10° C. to −30° C. for 3 hr. The suspension was cooled to −60° C. and MeOH (500 μL) was added to quench residual LAH. The resulting suspension was warmed to 0° C. and H2O (0.175 mL), 5N NaOH (0.175 mL), followed by H2O (0.525 mL) was added in order. The suspension was stirred overnight at 23° C., filtered, rinsed with THF (3×10 mL) and MeOH (3×10 mL). The filtrate was concentrated via rotary evaporation, re-constituted in THF (50 mL), neutralized to pH 4-5 with 3N HCl (1.5 mL). The green, turbid solution was partitioned with brine (25 mL). The aqueous layer was washed with THF (2×25 mL), the organic extracts were combined, dried over Na2SO4, filtered, rinsed with THF and concentrated in vacuo. The resulting crude material was purified via medium pressure chromatography using a gradient eluant of CH2Cl2/MeOH. The appropriate fractions were combined and concentrated via rotary evaporation to provide 3-(hydroxymethyl)pyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-6(5H)-one (0.312 g, 1.450 mmol, 56.9% yield) as a green solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.59 (d, J=5.56 Hz, 2 H) 5.45 (t, J=5.68 Hz, 1 H) 6.73 (dd, J=3.54, 3.03 Hz, 1 H) 7.06 (dd, J=3.54, 1.77 Hz, 1 H) 7.54-7.59 (m, 1 H) 7.67 (dd, J=3.03, 1.52 Hz, 1 H) 8.34 (d, J=1.77 Hz, 1 H) 11.66 (s, 1 H). ESI-MS: m/z 216.1 (M+H)+.

Provenance & Evidence