Formic Acid → HCID 59514507, compound

Temperature

60 °C

To acetic anhydride (0.48 mL, 5.13 mmol) at 0° C. under Ar atmosphere was added formic acid (0.24 mL, 6.31 mmol) dropwise followed by heating of the mixture at 60° C. for 2 hours. After cooling to room temperature, THF (1 mL) was added followed by a solution of methyl [2-(4-aminobenzyl)-4-chloro-6-(dimethylamino)pyrimidin-5-yl]acetate (0.660 g, 1.97 mmol) in THF (1 ml). This was then stirred for 3 hours and concentrated to dryness. The remaining residue was dissolved in THF and cooled to 0° C. followed by the dropwise addition of borane dimethyl sulfide complex until the vigorous effervescence ceased. The mixture was gently refluxed for 14 hours and then cooled to 0° C. Methanol was added and the mixture was stirred at room temperature for 1 hour followed by the addition of concentrated HCl to pH ˜5 and stirring was continued for another 30 minutes. The solvent was evaporated in vacuo, the remaining residue basified with water and 1N NaOH, and the aqueous layer was extracted with Et2O. The combined organic extracts was dried over anhydrous Na2SO4, filtered, and concentrated to dryness to give the crude product which was chromatographed onver silica gel eluting with 5% acetone in CH2Cl2 to give methyl {4-chloro-6-(dimethylamino)-2-[4-(methylamino)benzyl]pyrimidin-5-yl}acetate (0.260 g, 38% yield) as a pale yellow oil.

1. temperatureAfter cooling to room temperature
2. concentrationconcentrated to dryness
3. dissolutionThe remaining residue was dissolved in THF
4. temperaturecooled to 0° C.
5. additionfollowed by the dropwise addition of borane dimethyl sulfide complex until the vigorous effervescence
6. temperatureThe mixture was gently refluxed for 14 hours
7. temperaturecooled to 0° C
8. additionMethanol was added
9. stirringthe mixture was stirred at room temperature for 1 hour
10. additionfollowed by the addition of concentrated HCl to pH ˜5
11. stirringstirring
12. waitwas continued for another 30 minutes
13. customThe solvent was evaporated in vacuo
14. extractionthe aqueous layer was extracted with Et2O
15. dry with materialThe combined organic extracts was dried over anhydrous Na2SO4
16. filtrationfiltered
17. concentrationconcentrated to dryness
18. customto give the crude product which
19. customwas chromatographed onver silica gel eluting with 5% acetone in CH2Cl2

ORD record

ord-151a4ee74ab049a4a2537664b3b54613

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07812160B2