2-Butyn-1-ol → HCID 58792128, compound

In 4 ml of N,N-dimethylformamide was dissolved 333 mg of 5-chloro-3-methylthio-1,2,4-thiadiazole, and 142 mg of pyrrolidine was added dropwise at room temperature. The mixture was stirred for 6 hours. The reaction mixture was diluted with tert-butyl methyl ether, and extracted with tert-butyl methyl ether after the addition of 10% hydrochloric acid. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude 3-methylthio-5-(pyrrolidin-1-yl)-1,2,4-thiadiazole. In 4 ml of chloroform was added the crude 3-methylthio-5-(pyrrolidin-1-yl)-1,2,4-thiadiazole, and 1.52 g of 3-chloroperbenzoic acid (content: 65 weight %) was added under ice-cooling. The mixture was stirred at room temperature for 6 hours. The reaction mixture was washed with 10%-sodium sulfite aqueous solution and saturated sodium bicarbonate aqueous solution. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude mixture of 3-methylsulfinyl-5-(pyrrolidin-1-yl)-1,2,4-thiadiazole and 3-methylsulfonyl-5-(pyrrolidin-1-yl)-1,2,4-thiadiazole. The crude mixture of 3-methylsulfinyl-5-(pyrrolidin-1-yl)-1,2,4-thiadiazole and 3-methylsulfonyl-5-(pyrrolidin-1-yl)-1,2,4-thiadiazole was mixed with 4 ml of N,N-dimethylformamide and 140 mg of 2-butyn-1-ol, and 120 mg sodium hydride (oil suspension; content: 60 weight %) under ice-cooling. The mixture was stirred for 15 minutes and at room temperature for 6 hours. The reaction mixture was extracted with tert-butyl methyl ether after the addition of saturated sodium chloride aqueous solution. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 158 mg of 3-(2-butynyloxy)-5-(pyrrolidin-1-yl)-1,2,4-thiadiazole (hereinafter, referred to as the present compound (1)).

1. additionwas added dropwise at room temperature
2. extractionextracted with tert-butyl methyl ether
3. additionafter the addition of 10% hydrochloric acid
4. washThe organic layer was washed with water
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customto obtain a crude 3-methylthio-5-(pyrrolidin-1-yl)-1,2,4-thiadiazole
8. additionwas added under ice-
9. temperaturecooling
10. stirringThe mixture was stirred at room temperature for 6 hours
11. washThe reaction mixture was washed with 10%-sodium sulfite aqueous solution and saturated sodium bicarbonate aqueous solution
12. dry with materialThe organic layer was dried over anhydrous sodium sulfate
13. concentrationconcentrated under reduced pressure
14. customto obtain a crude
15. temperaturecooling
16. stirringThe mixture was stirred for 15 minutes and at room temperature for 6 hours
17. extractionThe reaction mixture was extracted with tert-butyl methyl ether
18. additionafter the addition of saturated sodium chloride aqueous solution
19. dry with materialThe organic layer was dried over anhydrous sodium sulfate
20. concentrationconcentrated under reduced pressure

ORD record

ord-c62d10b3b7f64cdcb0ca6f8e195b5776

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07371746B2