Methanesulfonyl chloride → methanesulfonic acid 3-(3-cyano-1H-indol-5-yl)-3-phenyl-propyl ester

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Reaction Conditions

Reaction Steps

To a 0° C. solution of 5-(3-hydroxy-1-pheny-propyl)-1H-indole-3-carbonitrile LXV (600 mg, 2.17 mmol) in THF/DCM (1/1, 12 ml) was added dropwise MsCl (168 μl, 2.17 mmol). The mixture was stirred at 0° C. for 10 min and TEA (360 μl, 2.58 mmol) was added dropwise. The resulting mixture was stirred at 0° C. for 2 hours, diluted with THF (6 ml), stirred at 0° C. for additional 2 hours, poured into an ice/water mixture, and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated affording the metanesulfonic acid 3-(3-cyano-1H-indol-5-yl)-3-phenyl-propyl ester as a yellow oil. A solution of this mesylate in MeNH2 (33% in EtOH, 10 ml) was heated in a sealed tube at 100° C. for 1 hour. The mixture was concentrated, and the residue was partitioned between a saturated solution of NaHCO3 and DCM. The aqueous layer was extracted twice with DCM. The combined organic layers were dried over Na2SO4, filtered, concentrated and purified via flash chromatography (DCM/MeOH/NH4OH) affording 5-(3-methylamino-1-pheny-propyl)-1H-indole-3-carbonitrile LXVI as a white solid (156 mg). MS (M+H)=290.

Provenance & Evidence