Ethylamine → HCID 66744037, compound

A mixture of 1,2,2-trimethyl-4-oxo-1,2,3,4-tetrahydrothieno[3,2-d]pyrimidine-6-carbaldehyde (100 mg, 0.446 mmol), MS4A powder (100 mg) and 2 M ethylamine in THF (2.00 mL, 4.00 mmol) was stirred for 1 h at room temperature. Then, the mixture was concentrated under reduced pressure to give a yellow solid. Then, the residue was suspended with 2 M ethylamine in THF (2.00 mL, 4.00 mmol) and MgSO4 (100 mg). The mixture was stirred overnight and concentrated under reduced pressure to give yellow solid. Then, the residue was suspended with 2 M ethylamine in THF (2.00 mL, 4.00 mmol). The mixture was stirred for 4 h and concentrated under reduced pressure to give yellow solid. Then, 1-[(isocyanomethyl)sulfonyl]-4-methylbenzene (131 mg, 0.669 mmol), potassium carbonate (123 mg, 0.892 mmol) and MeOH (3 mL) were added to the residue, and the mixture was stirred at 60° C. for 1 h. 1-[(Isocyanomethyl) sulfonyl]-4-methylbenzene (131 mg, 0.669 mmol) and potassium carbonate (123 mg, 0.892 mmol) were added again, and the mixture was stirred at 60° C. overnight. 1-[(Isocyanomethyl) sulfonyl]-4-methylbenzene (131 mg, 0.669 mmol) and potassium carbonate (123 mg, 0.892 mmol) were added again, and the mixture was stirred at 60° C. for 2 h. The mixture was poured into saturated aqueous NaHCO3 (80 mL) and extracted with EtOAc (80 mL), and the extract was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure to afford orange gum. This residue was purified by column chromatography (Purif, NH, 95:5 hexane/EtOAc to EtOAc) and preparative HPLC (YMC CombiPrep. Hydrosphere C18). The fractions containing the title compound were collected and basified by addition of saturated aqueous NaHCO3. Extraction with EtOAc, drying over MgSO4, filtration and concentration under reduced pressure gave the title compound (11.5 mg, 9.8%) as pale yellow solid:

1. concentrationThen, the mixture was concentrated under reduced pressure
2. customto give a yellow solid
3. stirringThe mixture was stirred overnight
4. concentrationconcentrated under reduced pressure
5. customto give yellow solid
6. stirringThe mixture was stirred for 4 h
7. concentrationconcentrated under reduced pressure
8. customto give yellow solid
9. stirringthe mixture was stirred at 60° C. for 1 h
10. stirringthe mixture was stirred at 60° C. overnight
11. stirringthe mixture was stirred at 60° C. for 2 h
12. extractionextracted with EtOAc (80 mL)
13. washthe extract was washed with brine
14. dry with materialdried over MgSO4
15. filtrationfiltered
16. concentrationconcentrated under reduced pressure
17. customto afford orange gum
18. customThis residue was purified by column chromatography (Purif, NH, 95:5 hexane/EtOAc to EtOAc) and preparative HPLC (YMC CombiPrep. Hydrosphere C18)
19. additionThe fractions containing the title compound
20. customwere collected
21. additionbasified by addition of saturated aqueous NaHCO3
22. extractionExtraction with EtOAc
23. dry with materialdrying over MgSO4, filtration and concentration under reduced pressure

ORD record

ord-f1acdf5f75384bbabb7caf53f07b518c

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2