反应详情

温度

120 °C

A microwave vial was charged with Solvias catalyst (8 mg), tripotassium phosphate (90 mg) and 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (available from ABCR, 24 mg). 1-(1-Methylethyl)-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1H-pyrazole-5-carboxamide (70 mg) in 1,4-dioxane (0.5 ml) was added followed by water (0.1 ml). The reaction was heated under microwave irradiation at 120° C. for 10 min. Solvias catalyst (8 mg) was added and the reaction heated under microwave irradiation at 120° C. for 10 min. Further Solvias catalyst (8 mg) and tripotassium phosphate (30 mg) were added and the reaction was heated under microwave irradiation at 120° C. for 30 min. Again further Solvias catalyst (8 mg) and tripotassium phosphate (90 mg) were added and the reaction was heated under microwave irradiation at 120° C. for 30 min. 4-Chloro-1H-pyrrolo[2,3-d]pyrimidine (12 mg) was added and the reaction was heated under microwave irradiation at 120° C. for 30 min. Addition of catalyst and base was repeated and the reaction was heated under microwave irradiation at 120° C. for 30 min. The reaction was passed through a silica cartridge preconditioned with methanol, washing with methanol, then dried under a stream of nitrogen. The residue was subjected to a DCM/water wash and then dried under a stream of nitrogen. The residue was dissolved in DMSO:methanol (1 ml, 1:1, v/v) and purified by MDAP (method A). The appropriate fraction was evaporated under a stream of nitrogen. The residue was dissolved in methanol, a few drops of 2M HCl (aq) were added and the mixture was left to stand briefly at room temperature, then evaporated under a stream of nitrogen. Sequential purification was carried out using the following system and the two gradients shown:

1. temperaturethe reaction heated under microwave irradiation at 120° C. for 10 min
2. temperaturethe reaction was heated under microwave irradiation at 120° C. for 30 min
3. temperaturethe reaction was heated under microwave irradiation at 120° C. for 30 min
4. temperaturethe reaction was heated under microwave irradiation at 120° C. for 30 min
5. additionAddition of catalyst and base
6. temperaturethe reaction was heated under microwave irradiation at 120° C. for 30 min
7. washwashing with methanol
8. customdried under a stream of nitrogen
9. washwash
10. customdried under a stream of nitrogen
11. dissolutionThe residue was dissolved in DMSO
12. custommethanol (1 ml, 1:1, v/v) and purified by MDAP (method A)
13. customThe appropriate fraction was evaporated under a stream of nitrogen
14. dissolutionThe residue was dissolved in methanol
15. additiona few drops of 2M HCl (aq) were added
16. waitthe mixture was left
17. customto stand briefly at room temperature
18. customevaporated under a stream of nitrogen
19. customSequential purification