反应详情

温度

85 °C

A suspension of 2-methyl-2H-indazol-6-ylamine [Davies J. Chem. Soc.; 1955; 2412-2419] (809 mg, 5.5 mmol) in DCE (13.5 mL) was treated at 0° C. consecutively with, trimethylaluminium (2 M) in toluene (4.23 mL, 8.46 mmol), 2-{[2-(3-methyl-ureido)-pyridin-4-ylmethyl]-amino}-nicotinic acid methyl ester (1.34 g, 4.23 mmol) and DCE (20 mL). The reaction mixture was placed under a nitrogen atmosphere and heated for 10 hours at 85° C. (bath temperature). On cooling the reaction was poured into aqueous sodium-potassium tartrate solution (150 mL) and partitioned between EtOAc and water. The organic phase was washed with brine, dried, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel (Gradient elution: 100% CH2Cl2 to 90% CH2Cl2/10% MeOH) to give N-(2-methyl-2H-indazol-6-yl)-2-{[2-(3-methyl-ureido)-pyridin-4-ylmethyl]-amino}-nicotinamide (964 mg, 53%) as a solid; Mp. 205-207° C.

1. temperatureOn cooling the reaction
2. custompartitioned between EtOAc and water
3. washThe organic phase was washed with brine
4. customdried
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by chromatography on silica gel (Gradient elution: 100% CH2Cl2 to 90% CH2Cl2/10% MeOH)