反应详情

To a suspension of 4-(2-methylbenzyl)-isonipecotic acid methyl ester hydrochloride (50 mg, 0.176 mmol) in toluene (2 ml) was added phosgene (0.912 ml of a 1.93M solution in toluene, 1.76 mmol) and triethylamine (0.074 ml, 0.528 mmol) and the mixture stirred for 48 hrs at room temperature. The excess phosgene was removed by purging the solution with argon gas for 10 min. The suspension was added to 1-(4-cyanobenzyl)-5-amino-1H-imidazole hydrochloride (100 mg, 0.528 mmol) in CH2Cl2 (10 ml) and the mixture stirrred at 50° C. for 72 hrs. The solvent was evaporated in vacuo and the residue purified by preparative HPLC (C18, 95:5 to 5:95 water: acetonitrile containing 0.1% TFA). The residue after lyophilisation was partitioned between CH2Cl2 and saturated NaHCO3 solution. The organic extract was dried (MgSO4), and evaporated to dryness

1. customThe excess phosgene was removed
2. customby purging the solution with argon gas for 10 min
3. waitthe mixture stirrred at 50° C. for 72 hrs
4. customThe solvent was evaporated in vacuo
5. customthe residue purified by preparative HPLC (C18, 95:5 to 5:95 water: acetonitrile containing 0.1% TFA)
6. customThe residue after lyophilisation was partitioned between CH2Cl2 and saturated NaHCO3 solution
7. extractionThe organic extract
8. dry with materialwas dried (MgSO4)
9. customevaporated to dryness