反应详情

温度

40 °C

To a solution of (7R)-7-[{2-[(tert-butoxycarbonyl)amino]ethyl}(methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylic acid (0.15 M) in DCM were added sequentially EDC (1.8 eq), N-(2,2-dimethoxyethyl)-N-methylsulfamide (1.8 eq) (prepared as described in Step 1) and DMAP (1.2 eq). The mixture was stirred at 40° C. for 1.5 hours. Further EDC (0.48 eq) and sulfamide (0.5 eq) were introduced and heating continued for 1 h. The reaction was left to cool with stirring overnight. The reaction was diluted with EtOAc and washed with 1N HCl (aq). The aqueous was extracted with EtOAc and the organics combined, washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to leave a brown gum. The residue was purified by RP-HPLC (Waters Xterra column; MeCN/H2O/0.1% TFA gradient). Fractions containing the pure compound were combined and lyophilized to afford the product as a white powder (44%). MS (ES+) m/z 728 (M+H)+.

1. temperatureheating
2. waitcontinued for 1 h
3. waitThe reaction was left
4. temperatureto cool
5. stirringwith stirring overnight
6. washwashed with 1N HCl (aq)
7. extractionThe aqueous was extracted with EtOAc
8. washwashed with brine
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customto leave a brown gum
13. customThe residue was purified by RP-HPLC (Waters Xterra column; MeCN/H2O/0.1% TFA gradient)
14. additionFractions containing the pure compound