Lithium triethylborohydride → (9H-fluoren-9-yl)methyl(R)-1-((S)-1-((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)allylamino)-1-oxopropan-2-ylamino)-3-methyl-1-oxobutan-2-ylcarbamate

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Reaction Conditions

Reaction Steps

SEM Fmoc amine 18e (0.245 g, 0.170 mmol, 1.0 eq) was solubilised in THF (10.6 mL) and cooled to −78° C. under a nitrogen atmosphere. Super hydride solution (0.347 mL, 0.347 mmol, 2.04 eq) was added drop wise over 4 minutes. After 45 minutes an aliquot was diluted with water and MeOH for LCMS After stirring for a further 10 minutes, the reaction mixture was diluted with water (35 mL) and the cold bath removed. The organic layer was extracted with EtOAc (2×35 mL) and the combined organic extracts washed with brine (35 mL), dried with MgSO4, filtered and concentrated under reduced pressure. The crude material was dissolved in MeOH (12.8 mL), DCM (6.4 mL) and water (2.15 mL) and enough silica gel was added to form a thick suspension which was left stirring for 5 days. The suspension was filtered and washed with DCM/MeOH 9:1 (˜200 mL) until complete elution of product. The organic layer was washed with brine (2×100 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (silica gel; 40:1 v/v DCM/MeOH to 20:1 v/v DCM/MeOH) to afford the product (0.100 g, 51%). LC/MS (2.117 min (ES+)), m/z: 575.7 ½[M+2H]+.

Provenance & Evidence