反应详情

0.321 g of cis-6-(4-tert-butoxycarbonylcyclohexyloxy)nicotinic acid (1 mmol, 1 eq.) is placed in 50 mL of acetonitrile at room temperature. 0.33 mL of diisopropylethylamine (2 mmol, 2 eq.), 0.466 g of bromotris-pyrrolidinophosphonium hexafluorophosphonate (1 mmol, 1 eq.) and 0.270 g of 5-(3-chlorobenzyl)[1.3.4]thiadiazol-2-ylamine (1.2 mmol, 1.2 eq.) are successively added with stirring. After 4 days at room temperature, the reaction medium is evaporated and 15 mL of DMF are added. The medium is stirred again for 18 hours, diluted in ethyl acetate, washed three times with brine, dried over magnesium sulfate, filtered and evaporated. The residue is chromatographed on silica gel, eluting with a gradient of ethyl acetate in heptane ranging from 5% to 50%. After evaporating the fractions of interest, the residue is chromatographed on silica gel with a gradient of ethyl acetate in dichloromethane ranging from 2% to 20%. 0.262 g of tert-butyl cis-4-{5-[5-(3-chlorobenzyl)[1.3.4]thiadiazol-2-ylcarbamoyl]pyridin-2-yloxy}cyclohexanecarboxylate is obtained.

1. customthe reaction medium is evaporated
2. addition15 mL of DMF are added
3. stirringThe medium is stirred again for 18 hours
4. additiondiluted in ethyl acetate
5. washwashed three times with brine
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. customevaporated
9. customThe residue is chromatographed on silica gel
10. washeluting with a gradient of ethyl acetate in heptane ranging from 5% to 50%
11. customAfter evaporating the fractions of interest
12. customthe residue is chromatographed on silica gel with a gradient of ethyl acetate in dichloromethane ranging from 2% to 20%