Isopropyl isocyanate → (3aR,7S,10S,12R,21E,24aS)-7-cyclopentyl-10-({(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}carbamoyl)-5,8-dioxo-1,2,3,3a,5,6,7,8,11,12,20,23,24,24a-tetradecahydro-10H-9,12-methanocyclopenta[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinolin-19-yl propan-2-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of (3aR,7S,10S,12R,21E,24aS)-7-cyclopentyl-N-{(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-19-hydroxy-5,8-dioxo-1,2,3,3a,5,6,7,8,11,12,20,23,24,24a-tetradecahydro-10H-9,12-methanocyclopenta[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoline-10-carboxamide (Example 17) (30 mg) in dichloroethane (0.6 mL) was added isopropylisocyanate (0.037 mL) then DMAP (4.6 mg). The reaction mixture was heated to 50° C. for 1 hour. After cooling back to room temperature, the mixture was diluted with ethyl acetate and water was added. The mixture was extracted with ethyl acetate (3×). The combined organics were dried over magnesium sulfate, filtered and concentrated. Purification by reverse phase HPLC (40% ACN-100% ACN/0.05% TFA/water) yielded 27 mg of the desired product after workup with NaHCO3 and ethyl acetate. HRMS (ES+) m/z 875.3981 (M+H)+.

Provenance & Evidence