Hydrochloric Acid → HCID 66547737, compound

Participants

Reaction Conditions

Reaction Steps

14.5 mg (16 μmol) N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S,3Z)-1,5-diphenylpent-3-en-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide trifluoroacetic acid salt (intermediate 17) was dissolved in 1 mL dioxane/water (1:1) and mixed with 20.4 μL (32 μmol) of a 15% aqueous solution of 4-oxobutanoic acid. The batch was then stirred for one hour at 100° C. After cooling to RT, 1.1 mg (17 μmol) sodium cyanoborohydride was added and the mixture was adjusted to a pH of 3 by adding approx. 150 μL 0.1N hydrochloric acid. The batch was then stirred for two hours more at 100° C. Then 1.1 mg (17 μmol) sodium cyanoborohydride was added again and the mixture was next adjusted to a pH of 3 by adding approx. 300 μL 0.1N hydrochloric acid. The batch was then stirred again for two hours at 100° C. If the reaction was still incomplete, this procedure was repeated once more. Finally, the batch was concentrated and the raw product was purified by preparative HPLC and lyophilized from dioxane, thereby yielding 13.1 mg (93% of the theoretical) of the title compound in the form of a white solid.

Provenance & Evidence