Triethylamine → 6-bromo-2-(1-pyrrolidin-1-ylethyl)thieno[3,2-d]pyrimidin-4(3H)-one

To a mixture of 3-amino-5-bromothiophene-2-carboxamide (221 mg) produced in Example 1, step D, triethylamine (0.15 mL) and tetrahydrofuran (5.0 mL) was added 2-bromopropanoylchloride (0.11 mL) with stirring at room temperature. After 10 min, pyrrolidine (0.42 mL) was added, and the mixture was stirred at 70° C. for 1 hr. The reaction system was concentrated under reduced pressure, 2M aqueous sodium hydroxide solution (1.0 mL) was added to the residue, and the mixture was stirred with heating at 120° C. for 2 hr. The mixture was extracted with ethyl acetate and dried over anhydrous sodium sulfate. Insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate/hexane and methanol/ethyl acetate) to give the title compound (276 mg) as a pale-yellow solid.

1. stirringthe mixture was stirred at 70° C. for 1 hr
2. concentrationThe reaction system was concentrated under reduced pressure, 2M aqueous sodium hydroxide solution (1.0 mL)
3. additionwas added to the residue
4. stirringthe mixture was stirred
5. temperaturewith heating at 120° C. for 2 hr
6. extractionThe mixture was extracted with ethyl acetate
7. dry with materialdried over anhydrous sodium sulfate
8. customInsoluble material was removed by filtration
9. concentrationthe filtrate was concentrated under reduced pressure
10. customThe residue was purified by basic silica gel column chromatography (ethyl acetate/hexane and methanol/ethyl acetate)

ORD record

ord-0ec776e5758d47d4a78bfb895007ce47

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08722660B2