反应详情

温度

120 °C

N-[5-Bromo-2-(methyloxy)-3-pyridinyl]cyclopropanesulfonamide (208 mg, 0.371 mmol), 2-methyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide (128 mg, 0.417 mmol) and Pd(PPh3)4 (43 mg, 0.037 mmol) were weighed to a microwave vial. DMF (3 ml) was added and the reaction was heated in the microwave at 120° C. for 30 min. LCMS showed incomplete reaction, therefore the mixture was reheated at 120° C. for a further 30 min. The residue was passed through a 1 g silica cartridge, pre-conditioned with methanol, washing with methanol. The solvent was evaporated in the blow down unit. The residue was purified on a 40 g silica cartridge on the ISCO Companion, using a 0.5-6% methanol in DCM gradient over 14 mins at a flow rate of 40 ml/min. Fractions containing desired material were combined and concentrated in vacuo, then subjected to further purification on the ISCO companion using a reverse phase 13 g column, with 0.1% TFA in MeCN and 0.1% TFA in water as eluents and a gradient of 15-65% MeCN over 14 mins. Fractions containing desired material were combined and concentrated in vacuo. The residue was dissolved in IPA (3 ml) and 2M NaOH (aq., 3 ml) was added and the reaction mixture left overnight. The IPA was evaporated and the aqueous was acidified using 2M HCl (aq). The precipitate was filtered, washing with water, then dissolved in 1 ml DMSO:methanol (1:1, v/v) and purified by MDAP (Method E) to afford the title compound (27 mg).

1. customreaction
2. washwashing with methanol
3. customThe solvent was evaporated in the blow down unit
4. customThe residue was purified on a 40 g silica cartridge on the ISCO Companion
5. customover 14 mins
6. additionFractions containing desired material
7. concentrationconcentrated in vacuo
8. customsubjected to further purification on the ISCO companion
9. waitwith 0.1% TFA in MeCN and 0.1% TFA in water as eluents and a gradient of 15-65% MeCN over 14 mins
10. additionFractions containing desired material
11. concentrationconcentrated in vacuo
12. dissolutionThe residue was dissolved in IPA (3 ml)
13. addition2M NaOH (aq., 3 ml) was added
14. waitthe reaction mixture left overnight
15. customThe IPA was evaporated
16. filtrationThe precipitate was filtered
17. washwashing with water
18. dissolutiondissolved in 1 ml DMSO:methanol (1:1
19. customv/v) and purified by MDAP (Method E)