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

Temperature

0 °C

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)+.

1. temperatureThe suspension was cooled to −78° C.
2. stirringThe reaction was stirred at −10° C. to −30° C. for 3 hr
3. temperatureThe suspension was cooled to −60° C.
4. customto quench residual LAH
5. temperatureThe resulting suspension was warmed to 0° C.
6. additionwas added in order
7. stirringThe suspension was stirred overnight at 23° C.
8. filtrationfiltered
9. washrinsed with THF (3×10 mL) and MeOH (3×10 mL)
10. concentrationThe filtrate was concentrated via rotary evaporation, re-constituted in THF (50 mL)
11. customThe green, turbid solution was partitioned with brine (25 mL)
12. washThe aqueous layer was washed with THF (2×25 mL)
13. dry with materialdried over Na2SO4
14. filtrationfiltered
15. washrinsed with THF
16. concentrationconcentrated in vacuo
17. customThe resulting crude material was purified via medium pressure chromatography
18. concentrationconcentrated via rotary evaporation

ORD record

ord-7874652529f842088f9e386783965598

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08541417B2