Hydrochloric Acid → HCID 66743324, compound

A mixture of 1-ethyl-2-methyl-6-(5-methyl-1H-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (120 mg, 0.335 mmol) and TFA (1.0 mL) was stirred at room temperature for 1 day. After removal of the solvent at reduced pressure, the residue was treated with saturated aqueous NaHCO3. The organic materials were extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, EtOAc) to give a yellow crystalline solid. The solid was dissolved in DMA (1.5 mL). To the mixture, 2,2-dimethoxypropane (1.5 mL), CSA (15 mg) and MgSO4 (100 mg) were added. The mixture was stirred at 80° C. for 2 h. The mixture was poured into saturated aqueous NaHCO3. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, EtOAc) to give a yellow crystalline solid. The solid was mixed with MeOH (1.0 mL) and 1 M aqueous HCl (1.0 mL). After stirring at 50° C. for 1 h, saturated aqueous NaHCO3 was added to the mixture. The organic materials were extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was dissolved in acetic acid (0.50 mL). To the solution were added acetone (1.0 mL) and PTSA (10 mg). After stirring at 60° C. for 1 h, saturated aqueous NaHCO3 and EtOAc were added to the mixture. The organic materials were extracted with EtOAc. The combined extracts were washed with brine, and then dried over Na2SO4. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, 90:10 hexane/EtOAc to EtOAc), then crystallized from EtOAc/heptane to give the title compound (24 mg, 24%) as a colorless solid:

1. customAfter removal of the solvent at reduced pressure
2. additionthe residue was treated with saturated aqueous NaHCO3
3. extractionThe organic materials were extracted with EtOAc
4. washThe combined extracts were washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. customAfter removal of the solvent at reduced pressure
8. customthe residue was purified by column chromatography (Purif, silica gel, EtOAc)
9. customto give a yellow crystalline solid
10. stirringThe mixture was stirred at 80° C. for 2 h
11. extractionThe organic materials were extracted with EtOAc
12. washThe combined extracts were washed with water and brine
13. dry with materialdried over Na2SO4
14. filtrationfiltered
15. customAfter removal of the solvent at reduced pressure
16. customthe residue was purified by column chromatography (Purif, silica gel, EtOAc)
17. customto give a yellow crystalline solid
18. stirringAfter stirring at 50° C. for 1 h
19. extractionThe organic materials were extracted with EtOAc
20. washThe combined extracts were washed with brine
21. dry with materialdried over Na2SO4
22. filtrationfiltered
23. customAfter removal of the solvent at reduced pressure
24. dissolutionthe residue was dissolved in acetic acid (0.50 mL)
25. additionTo the solution were added acetone (1.0 mL) and PTSA (10 mg)
26. stirringAfter stirring at 60° C. for 1 h
27. additionsaturated aqueous NaHCO3 and EtOAc were added to the mixture
28. extractionThe organic materials were extracted with EtOAc
29. washThe combined extracts were washed with brine
30. dry with materialdried over Na2SO4
31. customAfter removal of the solvent at reduced pressure
32. customthe residue was purified by column chromatography (Purif, silica gel, 90:10 hexane/EtOAc to EtOAc)
33. customcrystallized from EtOAc/heptane

ORD record

ord-34892069a9564d5f8a9eb889b6edd4c7

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2