Potassium Carbonate → HCID 57905085, compound

Temperature

23 °C

To ethyl 5-hydroxy-2-((2S,6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxylate (1.90 g, 6.37 mmol)in dry THF (60 mL) was added methanesulfonyl chloride (1.49 mL, 19.1 mmol) and di-isopropyl-ethylamine (3.56 mL, 20.0 mmol) at 0° C. The reaction mixture was stirred at 23° C. for 3 h. The THF was removed in vacuo, the crude material was dissolved in ethyl acetate (50 mL) and washed with 1N NaHCO3 (50 mL). The aqueous solution was then washed with ethyl acetate (3×20 mL) and the combined organic fractions were dried (MgSO4) filtered and concentrated in vacuo to give a brown oil. The crude oil was dissolved in EtOH:THF (20 mL:20 mL) and to this was added K2CO3 (0.881 g, 6.37 mmol) and H2O (1.0 mL). The reaction mixture was stirred at 65° C. for 17 h. The solvent was removed in vacuo, the crude material was dissolved in ethyl acetate (50 mL) and washed with H20 (50 mL) and HCl aq. 1N (50 mL). The acidic aqueous phase was extracted with ethyl acetate (2×50 mL). The combined organic fractions were dried (MgSO4) and concentrated in vacuo. The crude material was purified by preparative HPLC using a C18 column and trifluoroacetic acid in the mobile phase to afford the compound 1.16 g (65% yield) of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 10.75 (1 H, s), 4.94 (1 H, d, J=2.3 Hz), 4.49-4.58 (3 H, m), 4.01-4.13 (2 H, m), 2.05-2.17 (2 H, m,), 1.96 (1 H, dd, J=13.6, 2.0 Hz), 1.76 (2 H, m), 1.39-1.49 (4 H, m). LCMS (+ESI, M+H+) m/z 281. HRMS (ESI+) calculated for C13H16N2O5 [M+H+] :281.1137; found: 281.1147.

1. customThe THF was removed in vacuo
2. dissolutionthe crude material was dissolved in ethyl acetate (50 mL)
3. washwashed with 1N NaHCO3 (50 mL)
4. washThe aqueous solution was then washed with ethyl acetate (3×20 mL)
5. dry with materialthe combined organic fractions were dried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto give a brown oil
9. stirringThe reaction mixture was stirred at 65° C. for 17 h
10. customThe solvent was removed in vacuo
11. dissolutionthe crude material was dissolved in ethyl acetate (50 mL)
12. washwashed with H20 (50 mL) and HCl aq. 1N (50 mL)
13. extractionThe acidic aqueous phase was extracted with ethyl acetate (2×50 mL)
14. dry with materialThe combined organic fractions were dried (MgSO4)
15. concentrationconcentrated in vacuo
16. customThe crude material was purified by preparative HPLC

ORD record

ord-52760d740f3c47129e2d52e91833eb52

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129398B2