Ethyl bromoacetate → HCID 66743991, compound

To a solution of 6-bromo-3-(4-methoxybenzyl)-2,2-dimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (500 mg, 1.31 mmol) in DMF (13 mL) was added NaH (50%, 94 mg, 1.97 mmol) at 0° C. After stirring at room temperature for 15 min, ethyl bromoacetate (0.16 mL, 1.44 mmol) was added at once. After stirring at room temperature for 0.5 h, the mixture was poured into saturated aqueous NaHCO3. The organic materials were extracted with EtOAc. To the aqueous layer was added 1 M HCl until pH 5. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, and then dried over Na2SO4. After removal of the solvent at reduced pressure, the residual brown oil was mixed with N-ethyl-N-(1-methylethyl)propan-2-amine (0.24 mL, 1.37 mmol) and morpholine (0.072 mL, 0.82 mmol) in DMF (5 mL), and HATU (312 mg, 0.82 mmol) was added. After stirring at room temperature for 1 h, water and EtOAc were added to quench the reaction. 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, 95:5 hexane-EtOAc to EtOAc) to give a brown oil. After the oil was dissolved in TFA (2 mL), the mixture was stirred at 70° C. for 2 h. After removal of the solvent at reduced pressure, saturated aqueous NaHCO3 was added. 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 triturated with EtOAc and collected by filtration to afford the title compound (97 mg) as a brown solid. After concentration of the filtrate, the residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc then to 90:10 EtOAc/MeOH) to give the title compound (27 mg) as a brown solid. Total yield of the title compound (97+27 mg) was 27%:

1. stirringAfter stirring at room temperature for 0.5 h
2. extractionThe organic materials were extracted with EtOAc
3. additionTo the aqueous layer was added 1 M HCl until pH 5
4. extractionThe organic materials were extracted with EtOAc
5. washThe combined extracts were washed with water and brine
6. dry with materialdried over Na2SO4
7. customAfter removal of the solvent at reduced pressure
8. additionwas added
9. stirringAfter stirring at room temperature for 1 h
10. customto quench
11. customthe reaction
12. extractionThe organic materials were extracted with EtOAc
13. washThe combined extracts were washed with water and brine
14. dry with materialdried over Na2SO4
15. filtrationfiltered
16. customAfter removal of the solvent at reduced pressure
17. customthe residue was purified by column chromatography (Purif, silica gel, 95:5 hexane-EtOAc to EtOAc)
18. customto give a brown oil
19. stirringthe mixture was stirred at 70° C. for 2 h
20. customAfter removal of the solvent at reduced pressure, saturated aqueous NaHCO3
21. additionwas added
22. extractionThe organic materials were extracted with EtOAc
23. washThe combined extracts were washed with brine
24. dry with materialdried over Na2SO4
25. filtrationfiltered
26. customAfter removal of the solvent at reduced pressure
27. customthe residue was triturated with EtOAc
28. filtrationcollected by filtration

ORD record

ord-784f02052c3240369f31b1e10a5f8d79

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2