Tetrahydrothiopyran-4-one → HCID 86651594, compound

To a mixture of 2,4-dichloropyrimidin-5-amine (1.58 g, 9.63 mmol) and dihydro-2H-thiopyran-4 (3H)-one (1.45 g, 12.5 mmol) in dichloromethane (50 ml) at 0° C. was added dropwise a 1 M solution of titanium tetrachloride (10.6 ml, 10.6 mmol) in dichloromethane. After the reaction mixture was stirred at room temperature for 2 h, sodium cyanoborohydride (1.91 g, 28.9 mmol) was added in single portion and the reaction mixture was stirred at room temperature for 16 hours. After the reaction mixture was diluted with dichloromethane, the reaction mixture was poured carefully into iced-saturated NaHCO3 solution. EtOAc was added and then the insoluble materials were filtered off. The phases of the filtrate were separated, and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with water and saturated NaCl, dried with Na2SO4 and concentrated in vacuo to give a crude oil. The crude residue was purified by silica gel chromatography (hexane/ethyl acetate, 100:0 to 3:1) to afford 2,4-dichloro-N-(tetrahydro-2H-thiopyran-4-yl)pyrimidin-5-amine (864 mg, 3.27 mmol, 34% yield) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.59-1.76 (m, 2H) 2.07-2.20 (m, 2H) 2.58-2.69 (m, 2H) 2.70-2.85 (m, 2H) 3.42-3.57 (m, 1H) 5.78 (d, J=8.84 Hz, 1H) 8.25 (s, 1H). MS [M+H] 264.

1. stirringthe reaction mixture was stirred at room temperature for 16 hours
2. filtrationthe insoluble materials were filtered off
3. customThe phases of the filtrate were separated
4. extractionthe aqueous phase was extracted with EtOAc
5. washThe combined organic phases were washed with water and saturated NaCl
6. dry with materialdried with Na2SO4
7. concentrationconcentrated in vacuo
8. customto give a crude oil
9. customThe crude residue was purified by silica gel chromatography (hexane/ethyl acetate, 100:0 to 3:1)

ORD record

ord-a9a503db827c4a6cb56cc0c208f5c36e

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08268819B2