Tetrahydrofuran → 2-amino-6,6-dimethyl-4H,5H,6H,7H-[1,3]thiazolo[5,4-c]pyridin-4-one

To a stirred suspension of Intermediate 3 (0.50 g, 3.55 mmol) in THF (10 mL) was added Br2 (0.59 g, 0.19 mL, 3.72 mmol) dropwise at 0° C. The reaction mixture was then allowed to warm to r.t. and thiourea (0.27 g, 3.55 mmol), DIPEA (1.37 g, 1.85 mL, 10.65 mmol) and THF (5 mL) were added. The reaction mixture was heated to 85° C. for 1 h, cooled to r.t., and then EtOAc (10 mL) and water (10 mL) were added. The aqueous layer was extracted with EtOAc (2×15 mL) and the combined organic layers were washed with aqueous sat. NaHCO3 solution (15 mL) and brine (3×15 mL), dried (MgSO4), filtered and concentrated in vacuo to give the title compound (0.37 g, 53%) as a yellow solid that was used without further purification. δH (DMSO-d6) 7.63 (2H, s), 7.17 (1H, s), 2.62 (2H, s), 1.23 (6H, s). LCMS (ES+) 198.0 (M+H)+.

1. temperatureThe reaction mixture was heated to 85° C. for 1 h
2. temperaturecooled to r.t.
3. extractionThe aqueous layer was extracted with EtOAc (2×15 mL)
4. washthe combined organic layers were washed with aqueous sat. NaHCO3 solution (15 mL) and brine (3×15 mL)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORDレコード

ord-c77852fee39642b39b722ba176ff13c2

出典データセット

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08242116B2