反应详情

A solution of N-(5-(3-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide (LXXXIV) (52 mg, 0.127 mmol), 5-(4-methylpiperazin-1-yl)pyridine-3,4-diamine (LVIII) (29 mg, 0.13 mmol) and sulfur (45 mg, 0.13 mmol) in dry DMF (10 mL) was heated at 140° C. overnight. The reaction was cooled and evaporated under vacuum. The viscous residue was dried overnight under vacuum. The solid was washed with cold water and dried under vacuum. The crude product (L V) was dissolved in DCM (5 mL) followed by Et3SiH (48 μL, 0.30 mmol) and slowly addition of TFA (2.5 mL) The reaction was stirred until TLC (10% MeOH/DCM) showed the reaction was complete. The reaction was evaporated under vacuum and the residue was treated with water, sonicated and then basified with aq. ammonia. The solids were filtered, washed with cold water and dried. The crude product was heated in EtOAc and filtered hot to remove impurities. The hot EtOAc solution was allowed to slowly cool to room temperature and filtered to give 3-methyl-N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-c]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide 1 as a pink solid (36 mg, 0.071 mmol, 59% yield). 1H NMR (DMSO-d6, 500 MHz) δ ppm 0.97 (d, 6H), 2.13 (m, 1H), 2.27 (m, 4H), 3.45 (m, 4H), 6.70 (s, 1H), 7.79 (dd, 2H), 8.36 (s, 1H), 8.62 (s, 1H), 8.65 (s, 1H), 8.66 (s, 1H), 8.84 (s, 1H), 10.26 (s, 1H), 12.97 (s, 1H), 13.82 (s, 1H); ESIMS found for C28H31N9O m/z 510.5 (M+H).

1. temperatureThe reaction was cooled
2. customevaporated under vacuum
3. customThe viscous residue was dried overnight under vacuum
4. washThe solid was washed with cold water
5. customdried under vacuum
6. dissolutionThe crude product (L V) was dissolved in DCM (5 mL)
7. customThe reaction was evaporated under vacuum
8. additionthe residue was treated with water
9. customsonicated
10. filtrationThe solids were filtered
11. washwashed with cold water
12. customdried
13. temperatureThe crude product was heated in EtOAc
14. filtrationfiltered hot
15. customto remove impurities
16. filtrationfiltered