Dicyclohexylcarbodiimide → 4-Methyl-3-(4-methyloxazol-5-yl)-1H-1,2,4-triazole-5(4H)-thione

Temperature

0 °C

This material (498 g, 1 wt) was dissolved in dry tetrahydrofuran (5 vol), under nitrogen, cooled to 0° C. DCC (1.62 wt, 1 eq) was added portionwise followed by HOBt (1.07 wt, 1 eq). The mixture was warmed to 25±2° C. and stirred for 30 min. 4-Methyl-3-thiosemicarbazide (0.83 wt, 1 eq) was then added and the mixture further stirred for 2 h at 25±2° C. The mixture was filtered and the cake was washed with fresh tetrahydrofuran (1 vol) and dried on the filter for a few hours. The cake was suspended in 1 M aqueous NaOH (13 vol) and heated to 70° C. for 30 min. After this time, the mixture was cooled to 25±2° C. and a solid was removed by filtration. The cake was washed with 1 M aqueous NaOH (10 vol). The combined mother liquors were cooled to 0° C. and acidified to ca. pH 5 with HCl (aqueous, 16%; NOTE: keep temperature while adding HCl below +10° C.). The suspended product was isolated by filtration washing with water (2×3 vol). The cake was dried at 40° C. for 18 h in high vacuum to obtain 4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (respectively a tautomeric form thereof; 290 g, 37%).

1. temperatureThe mixture was warmed to 25±2° C.
2. stirringthe mixture further stirred for 2 h at 25±2° C
3. filtrationThe mixture was filtered
4. washthe cake was washed with fresh tetrahydrofuran (1 vol)
5. customdried on the
6. filtrationfilter for a few hours
7. temperatureheated to 70° C. for 30 min
8. temperatureAfter this time, the mixture was cooled to 25±2° C.
9. customa solid was removed by filtration
10. washThe cake was washed with 1 M aqueous NaOH (10 vol)
11. temperatureThe combined mother liquors were cooled to 0° C.
12. customacidified to ca. pH 5 with HCl (aqueous, 16%; NOTE: keep temperature while adding HCl below +10° C.)
13. customThe suspended product was isolated by filtration
14. washwashing with water (2×3 vol)
15. customThe cake was dried at 40° C. for 18 h in high vacuum

ORD record

ord-d12986b3678f4ad7a7f2200f7cac9e09

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07855298B2