1,2-Dichloroethane → tert-butyl {2-{[(7R)-14-cyclohexyl-11-[({[(2,2-dimethoxyethyl)(methyl)amino]sulfonyl}amino)carbonyl]-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocin-7-yl}(methyl)amino]ethyl}carbamate

Participants

Reaction Conditions

Reaction Steps

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)+.

Provenance & Evidence