反应详情

A mixture of 100 mg (0.30 mmol, 1.0 eq.) of 7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid from Example 4A, 116 mg of TBTU (0.36 mmol, 1.2 eq.) and 0.132 ml (1.2 mmol, 4.0 eq.) of 4-methylmorpholine in 2.2 ml of DMF was admixed with 103 mg (0.60 mmol, 2.0 eq.) of methyl trans-4-(aminomethyl)cyclohexanecarboxylate, and the mixture was stirred at RT overnight. The reaction mixture was admixed with water and TFA and purified by means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.1% TFA). The product fractions were combined and concentrated. Subsequently, the residue was taken up in dichloromethane and a little methanol, and washed twice with saturated aqueous sodium hydrogencarbonate solution. The aqueous phase was extracted twice with dichloromethane. The combined organic phases were dried over sodium sulphate, filtered, concentrated and lyophilized. 67 mg of the target compound were obtained (46% of theory).

1. custompurified by means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.1% TFA)
2. concentrationconcentrated
3. washa little methanol, and washed twice with saturated aqueous sodium hydrogencarbonate solution
4. extractionThe aqueous phase was extracted twice with dichloromethane
5. dry with materialThe combined organic phases were dried over sodium sulphate
6. filtrationfiltered
7. concentrationconcentrated