1,2-Dichloroethane → (R)-(4'-chlorobiphenyl-2-yl)(1-(4-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonylcarbamoyl)phenyl)piperidin-4-yl)methyl diethyl phosphate, hydrochloride salt

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Reaction Steps

A mixture of (R)-4-(4-((4′-chlorobiphenyl-2-yl)(diethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoic acid (INTERMEDIATE 120, 371 mg, 0.66 mmol), (R)-4-(4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 69, 368 mg, 0.66 mmol), EDC (255 mg, 1.33 mmol), TEA (0.185 ml, 1.33 mmol), and DCE (5 ml) were stirred at r.t. for 2 hours. The mixture was diluted with DCM (15 ml) and adsorbed onto silica gel. Purification by column chromatography (ISCO, eluting with 0→10% MeOH/DCM over 19 minutes followed by elution with 0→10% 2M NH3/MeOH/DCM over 24 minutes) gave a residue which was further purified by reverse phase HPLC, according to the conditions:

Provenance & Evidence