反应详情

To a stirred solution of methyl 7H-indolo[2,1-a][2]benzazepine-10-carboxylate, 13-cyclohexyl, 6-carboxylic acid (200 mg, 0.48 mmol), 2-(piperazin-1-yl)pyrimidine (95 mg, 0.58 mmol) and triethylamine (0.20 mL, 1.45 mmol) in DMF (3 mL) was added HATU (220 mg, 0.58 mmol). The reaction mixture was stirred at rt for 2 h, diluted with H2O (˜6 mL) and the solids were collected by filtration, washed with H2O, dissolved into MeOH//THF (1:1, 4 mL) and treated with 1M aqueous NaOH (0.60 mL). The reaction mixture was stirred and heated at 80° C. with microwave irradiation for 20 min in a sealed tube, additional 1 M aqueous NaOH (0.10 mL.) was added and the reaction was reheated at 80° C. for 10 min. The clear solution was diluted with H2O (1 mL), neutralized with 1M aqueous HCl (0.70 mL) and concentrated to remove organic solvents. The resultant solids were collected by filtration, washed with H2O and dried under vacuum to yield 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6-[[4-(2-pyrimidinyl)-1-piperazinyl]carbonyl] (125 mg, 0.23 mmol, 48%) as a light yellow solid. LCMS: m/e 548 (M+H)+, ret time 1.52 min, column A, 2 minute gradient.

1. filtrationthe solids were collected by filtration
2. washwashed with H2O
3. dissolutiondissolved into MeOH//THF (1:1, 4 mL)
4. additiontreated with 1M aqueous NaOH (0.60 mL)
5. stirringThe reaction mixture was stirred
6. temperatureheated at 80° C. with microwave irradiation for 20 min in a sealed tube
7. additionadditional 1 M aqueous NaOH (0.10 mL.) was added
8. waitthe reaction was reheated at 80° C. for 10 min
9. additionThe clear solution was diluted with H2O (1 mL)
10. concentrationconcentrated
11. customto remove organic solvents
12. filtrationThe resultant solids were collected by filtration
13. washwashed with H2O
14. customdried under vacuum