6,7-Dihydro-4H-pyrano[4,3-d]thiazol-2-ylamine

Synthesis

GENERAL STEPS: Tetrahydro-4H-pyran-4-one (500 mg, 4.99 mmol), sulfur powder (160 mg, 4.99 mmol), cyanamide (210 mg, 4.99 mmol), and pyrrolidine (4 μL, 0.05 mmol) were dissolved in isopropanol (3 mL) and the reaction was stirred for 1.5 hours at room temperature. Upon completion of the reaction, the mixture was partitioned between water and ethyl acetate (EtOAc) and the aqueous phase was extracted with additional ethyl acetate. The organic phases were combined, washed sequentially with water and saturated brine and dried over anhydrous magnesium sulfate (MgSO). The crude product was purified by fast column chromatography eluting with a gradient of mixed solvents (0-10% MeOH) of dichloromethane (DCM) and methanol (MeOH) to afford 6,7-dihydro-4H-pyrano[4,3-D]thiazol-2-amine as a yellow oil, which was crystallized after standing (500 mg, 64% yield). Mass spectrum (MS): m/z = 156.9 ([M + H]+).

References

[1] Patent: WO2016/1341, 2016, A1. Location in patent: Page/Page column 85
[2] Patent: WO2009/67613, 2009, A1. Location in patent: Page/Page column 129