反应详情

温度

45 °C

5-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-2-fluorobenzoic acid (0.180 g, 0.40 mmol, Intermediate 124) was suspended in toluene (3 mL). Thionyl chloride (0.145 mL, 1.98 mmol, Aldrich) and 1drop of DMF were added and the mixture was heated to 45° C. for 15 min After cooling to room temperature, the mixture was concentrated in vacuo, and toluene was added, then the mixture was concentrated in vacuo again to give a dark yellow residue. After drying under high vacuum overnight the oil turned into a dark yellow film. This film was taken up in THF (2 mL). In separate flask ethyl 3-(dimethylamino)acrylate (0.074 g, 0.51 mmol, Acros) and triethylamine (0.082 mL, 0.59 mmol, Acros) were dissolved in THF (5 ml). The solution of the acid chloride in THF (2 ml) was added dropwise to acrylate solution, then the flask was placed in an oil bath preheated to 72° C. and stirred for 1 h. After cooling to room temperature, the mixture was diluted with EtOAc(10 mL) and water (10 mL). The layers were separated and the organic layer was washed with 1 N HCl, twice with water, once with brine, then dry over Na2SO4, filter and concentrated in vacuo to give crude product as an orange oil.

1. temperatureAfter cooling to room temperature
2. concentrationthe mixture was concentrated in vacuo, and toluene
3. additionwas added
4. concentrationthe mixture was concentrated in vacuo again
5. customto give a dark yellow residue
6. customAfter drying under high vacuum overnight the oil
7. customthe flask was placed in an oil bath
8. custompreheated to 72° C.
9. temperatureAfter cooling to room temperature
10. customThe layers were separated
11. washthe organic layer was washed with 1 N HCl, twice with water, once with brine
12. dry with materialdry over Na2SO4
13. filtrationfilter
14. concentrationconcentrated in vacuo
15. customto give crude product as an orange oil