反应详情

To a suspension of 5-bromobenzothiophene-2-carboxylic acid (109 mg, 0.42 mmol) in dichloromethane (5 mL) was added oxalyl chloride (2M in dichloromethane, 0.5 mL) and one drop of DMF. The mixture was stirred at room temperature for 1 hr and solvents were evaporated. The residue was diluted with benzene (10 mL) and then concentrated to dryness. The residue was dissolved in dichloromethane (5 mL) and treated with (S)-3-(5-amino-pyridin-2-ylamino)-pyrrolidine-1-carboxylic acid ethyl ester (106 mg, 0.42 mmol) in dichloromethane (5 mL) containing triethylamine (0.1 mL). The mixture was stirred at room temperature for 1 hr and solvents were evaporated. The residue was extracted with ethyl acetate and saturated ammonium chloride solution. Organic layer was washed with brine and dried over sodium sulfate. Solvents were evaporated and the residue was treated with methanol (1 mL) and hydrogen chloride in ether. Solvents were evaporated and the residue was treated with ether. The precipitate was filtered and washed with ether to give a light pink solid as (S)-3-{5-[(5-bromo-benzo[b]thiophene-2-carbonyl)-amino]-pyridin-2-ylamino}-pyrrolidine-1-carboxylic acid ethyl ester hydrochloride (100 mg, 48.3% yield). LCMS for C21H21BrN4O3S calcd. (m/e) 488, observed 489 (M+H).

1. customsolvents were evaporated
2. additionThe residue was diluted with benzene (10 mL)
3. concentrationconcentrated to dryness
4. dissolutionThe residue was dissolved in dichloromethane (5 mL)
5. stirringThe mixture was stirred at room temperature for 1 hr
6. customsolvents were evaporated
7. extractionThe residue was extracted with ethyl acetate and saturated ammonium chloride solution
8. washOrganic layer was washed with brine
9. dry with materialdried over sodium sulfate
10. customSolvents were evaporated
11. additionthe residue was treated with methanol (1 mL) and hydrogen chloride in ether
12. customSolvents were evaporated
13. additionthe residue was treated with ether
14. filtrationThe precipitate was filtered
15. washwashed with ether