反应详情

温度

2.5 °C

Add sodium hydride, 60% dispersion in mineral oil (55.0 g×60%=33.0 g, 1.38 mol) to THF (950 mL) with stirring at 0-5° C. under nitrogen. Add a solution of 2-amino-5-methyl-thiophene-3-carbonitrile (95.0 g, 0.687 mol) and 1,2,4-trifluoro-5-nitro-benzene (121.7 g, 0.687 mol) in THF (1325 mL) dropwise over ˜1 hour, keeping the temperature below 10° C. Allow the reaction to warm to ambient temperature and stir for 8-20 hours. Cool to 10-15° C. and add aqueous 1N HCl (550 mL) dropwise over 10-15 minutes to adjust the pH to 7.0-7.2, keeping the pot temperature below 15° C. Remove most of the organic portion under reduced pressure, and then filter and rinse with water. Dry at 50-60° C. to obtain the crude product. Purify by flash chromatography, eluting with 1:1/methylene chloride:heptane to give 89.1 g (44%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 9.77 (bs, 1H), 8.33 (m, 1H), 7.09 (s, 1H), 7.07 (m, 1H), 2.47 (s, 3H). HRMS (ES) exact mass M+H calcd for C12H7F2N3O2S 318.0125; found 318.0133.

1. customthe temperature below 10° C
2. customthe reaction
3. temperatureto warm to ambient temperature
4. stirringstir for 8-20 hours
5. temperatureCool to 10-15° C.
6. customthe pot temperature below 15° C
7. customRemove most of the organic portion under reduced pressure
8. filtrationfilter
9. washrinse with water
10. customDry at 50-60° C.
11. customto obtain the crude product
12. customPurify by flash chromatography
13. washeluting with 1:1/methylene chloride