Hydrochloric Acid → HCID 66749332, compound

Temperature

60 °C

To a solution of N-allyl-2,4-dibromo-1,3-thiazole-5-carboxamide (13.0 g, 39.9 mmol) in dichloromethane (260 mL) was added phosphorus pentachloride (9.93 g, 47.7 mmol) and 4M hydrochloric acid in dioxane (1.52 mL, 6.06 mmol). The reaction was heated to 60° C. for 90 minutes under an atmosphere on nitrogen. The reaction was allowed to cool to room temperature and then aminoacetaldehyde dimethyl acetal (47.8 mL, 439 mmol) was added slowly through the condenser. The mixture was heated to 60° C. for 2 hours under an atmosphere of nitrogen then cooled to room temperature, and water was added (200 mL). The layers were separated and the organic phase was washed with water again (2×200 mL). The organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and washed with dichloromethane (200 mL). To this dichloromethane solution of the intermediate was added 4M hydrochloric acid in dioxane (120 mL, 480 mmol) and the solution was stirred at 60° C. for 16 hours. The solution was decanted (leaving behind an oily black residue on the flask) then the solvent was evaporated and the residue was diluted with ethyl acetate and saturated sodium bicarbonate solution. The layers were separated and the aqueous phase was extracted three more times with ethyl acetate. The organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Column chromatography was performed to yield the title compound (8.04 g, 58%). LCMS: (FA) ES+ , 306 (parent minus allyl group). 1H NMR (300 MHz, d4-methanol) δ: 7.37-7.31 (m, 1H), 7.20-7.16 (m, 1H), 6.02-5.86 (m, 1H), 5.26-5.18 (m, 1H), 5.07-4.96 (m, 1H), 4.68-4.59 (m, 2H).

1. temperatureto cool to room temperature
2. temperatureThe mixture was heated to 60° C. for 2 hours under an atmosphere of nitrogen
3. temperaturethen cooled to room temperature
4. customThe layers were separated
5. washthe organic phase was washed with water again (2×200 mL)
6. washThe organic extracts were washed with brine
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. washwashed with dichloromethane (200 mL)
10. customThe solution was decanted (
11. customleaving behind an oily black residue on the flask) then the solvent
12. customwas evaporated
13. additionthe residue was diluted with ethyl acetate and saturated sodium bicarbonate solution
14. customThe layers were separated
15. extractionthe aqueous phase was extracted three more times with ethyl acetate
16. washThe organic extracts were washed with brine
17. dry with materialdried over anhydrous sodium sulfate
18. filtrationfiltered
19. concentrationconcentrated in vacuo

ORD record

ord-1721a48f39764c358ccc9d0d4dd35f0f

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796268B2