Lithium triethylborohydride → (9H-fluoren-9-yl)methyl(E)-3-((S)-7-methoxy-8-(3-((S)-7-methoxy-2-(4-(4-methylpiperazin-1-yl)phenyl)-5-oxo-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)propoxy)-5-oxo-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-2-yl)allylcarbamate

Participants

Reaction Conditions

Reaction Steps

SEM dilactam 14e (0.250 g, 0.196 mmol, 1.0 eq.) was solubilised in THF (13 mL) and cooled to −78° C. under a nitrogen atmosphere. Super hydride solution (0.40 mL, 0.401 mmol, 2.04 eq.) was added dropwise over 5 min. After 20 min an aliquot was washed with water for LCMS and TLC analysis. After 30 mins water (30 mL) was added and the cold bath removed. The organic layer was extracted with EtOAc (2×40 mL) and the combined organic extracts washed with brine (40 mL), dried with MgSO4, filtered and removed under reduced pressure. The crude product was dissolved in MeOH (13 mL), DCM (7 mL) and water (1.7 mL) and enough silica gel to form a thick stirring suspension. After 5 days the suspension was filtered through a sintered funnel and washed with DCM/MeOH 9:1 (˜200 mL) until complete elution of product. The organic layer was washed with brine (2×70 mL), dried with MgSO4, filtered and the solvent removed under reduced pressure. Purification by flash chromatography (silica gel, CHCl3 100 to 96:4 v/v CHCl3/MeOH) afforded the product as a pale yellow solid (0.090 g, 47%). LC/MS (2.112 min (ES+)), m/z: 981.0 [M+H]+.

Provenance & Evidence