Ethanol → HCID 178518057, compound

Temperature

45 °C

Formamidine acetate (5, 1.04 Kg, 10 mol, 1.25 equiv) was added to 7.52 L of (21% wt) sodium ethoxide (EtONa) in ethanol (EtOH, 62.5 equiv) and the resulting solution was stirred for 60 minutes. 2-cyano-4,4-diethoxy-butyric acid ethyl ester (4, 1.8 Kg, 8.0 mol) was then added and the resulting reaction mixture was refluxed for seven hours. The stirring was turned off after the solution was cooled and the solids were allowed to settle. The supernatant ethanol solution was removed, leaving the solids in the bottom of the reaction flask. The ethanol was evaporated and the residue was added back to the solids remaining in the reaction flask with water and ice at a ratio of 600 mL/mol. A solution of 6 N aqueous HCl was added to the resulting solution at a ratio of 500 mL/mol at 15° C. The resulting solution was then heated at 45° C. for 45 minutes. The solution was again cooled to 15° C. and the pH was adjusted to 8.0 with the addition of aqueous ammonium hydroxide. The precipitated solids were collected by filtration, washed with water (2×225 mL/mol) and pulled dry. The solids were further washed with 1:1 ethyl acetate/heptane (500 mL/mol), then heptane (2×250 mL/mol) and dried in vacuum to afford 7H-pyrrolo[2,3-d]pyrimidin-4-ol (7, 738.6 g, 1081 g theoretical, 68.3%) as yellow to brown to yellow crystalline material. For 7: 1H NMR (DMSO-d6, 300 MHz) δ ppm 11.88 (bs, 1H), 11.80 (bs, 1H), 7.81 (s, 1H), 7.02 (dd, 1H, J=3.2, 2.3 Hz), 6.42 (dd, 1H, J=3.5, 2.3 Hz); C6H5N3O (MW, 135.12), LCMS (EI) m/e 136 (M++H) and (M++Na) m/e 158.

1. customthe resulting reaction mixture
2. temperaturewas refluxed for seven hours
3. temperaturewas cooled
4. customThe supernatant ethanol solution was removed
5. customleaving the solids in the bottom of the reaction flask
6. customThe ethanol was evaporated
7. additionthe residue was added back to the solids
8. additionA solution of 6 N aqueous HCl was added to the resulting solution at a ratio of 500 mL/mol at 15° C
9. temperatureThe solution was again cooled to 15° C.
10. additionthe pH was adjusted to 8.0 with the addition of aqueous ammonium hydroxide
11. filtrationThe precipitated solids were collected by filtration
12. washwashed with water (2×225 mL/mol)
13. custompulled dry
14. washThe solids were further washed with 1:1 ethyl acetate/heptane (500 mL/mol)
15. dry with materialheptane (2×250 mL/mol) and dried in vacuum

ORD record

ord-e0885015318a43f1bfb84c030b39face

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09290506B2