反应详情

温度

150 °C

Ethyl 2-[(4-methoxybenzyl)amino]-3-nitro-6-(trifluoromethyl)isonicotinate x193 (2.6 g, 6.5 mmol) is dissolved in methanol (100 ml), and Raney nickel (0.8 g) is added. The starting compound is hydrogenated in a Parr apparatus under a hydrogen pressure of 3 atm until the conversion of x193 is complete (1.5-2 h). The catalyst is filtered off and washed with methanol. The filtrate is evaporated to dryness. Triethyl orthoformate (100 ml) and p-toluene sulfonic acid (0.15 g) are added. The flask is equipped with a reflux condenser. The apparatus is flushed with argon, and the obtained reaction mixture is heated under vigorous stirring to 150° C. for 6 h. The reaction solution is evaporated in vacuum. The residue is partitioned between dichloromethane and a saturated aqueous solution of NaHCO3. The organic layer is dried with anhydrous sodium sulfate and evaporated. The target product is purified by chromatography on silicagel (dichloromethane/acetone) to afford 1.5 g of ethyl 3-(4-methoxybenzyl)-5-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine-7-carboxylate x196.

1. custom(1.5-2 h)
2. filtrationThe catalyst is filtered off
3. washwashed with methanol
4. customThe filtrate is evaporated to dryness
5. additionTriethyl orthoformate (100 ml) and p-toluene sulfonic acid (0.15 g) are added
6. customThe flask is equipped with a reflux condenser
7. customThe apparatus is flushed with argon
8. customthe obtained reaction mixture
9. temperatureis heated
10. customThe reaction solution is evaporated in vacuum
11. customThe residue is partitioned between dichloromethane
12. dry with materialThe organic layer is dried with anhydrous sodium sulfate
13. customevaporated
14. customThe target product is purified by chromatography on silicagel (dichloromethane/acetone)