反应详情

20.5 mg (0.11 mmol) of tert-butyl [1-(aminomethyl)cyclopropyl]carbamate were initially charged in a 96-well deep well multititre plate. A solution of 33.2 mg (0.1 mmol) of 7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid from Example 4A in 0.4 ml of DMF/dichloromethane (1:1, v/v) and a solution of 49.4 mg (0.13 mol) of HATU in 0.4 ml of DMF/dichloromethane (1:1, v/v) were added successively. After adding 20.2 mg (0.20 mmol) of 4-methylmorpholine, the mixture was shaken at RT overnight. Subsequently, the mixture was heated to 60° C. and shaken at this temperature for 7 h. Then the solvent was evaporated off completely. The residue was admixed with 0.6 ml of TFA and shaken at room temperature overnight. Then the mixture was concentrated fully, the residue was dissolved in 0.8 ml of DMF and filtered, and the target compound was isolated from the filtrate by preparative LC-MS (Method 9). The product-containing fractions were concentrated under reduced pressure using a centrifugal dryer. The residue of each product fraction was dissolved in 0.6 ml of DMSO. These were combined and finally freed of the solvent in a centrifugal dryer. 0.5 mg (1.3% of theory) of the title compound were obtained.

1. temperatureSubsequently, the mixture was heated to 60° C.
2. stirringshaken at this temperature for 7 h
3. customThen the solvent was evaporated off completely
4. stirringshaken at room temperature overnight
5. concentrationThen the mixture was concentrated fully
6. dissolutionthe residue was dissolved in 0.8 ml of DMF
7. filtrationfiltered
8. customthe target compound was isolated from the filtrate by preparative LC-MS (Method 9)
9. concentrationThe product-containing fractions were concentrated under reduced pressure
10. dissolutionThe residue of each product fraction was dissolved in 0.6 ml of DMSO