Methanesulfonyl chloride → Rac-methanesulfonic acid 3-{4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-2-hydroxy-propyl ester

Participants

Reaction Conditions

Reaction Steps

To a cooled (0° C.) solution of rac-3-{4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-propane-1,2-diol (619 mg, 1.54 mmol) in THF (15 mL), DIPEA (399 mg, 3.08 mmol) followed by methansulfonyl chloride (247 mg, 2.16 mmol) is added. The mixture is stirred at 0° C. for 1 h, then at rt for 1 h. The mixture is diluted with DCM, washed with brine (3×50 mL), dried over MgSO4, filtered, concentrated and dried to give crude rac-methanesulfonic acid 3-{4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-2-hydroxy-propyl ester (955 mg) as a light brown oil; LC-MS: tR=0.54 min; [M+1]+=480.10. b) A solution of the above rac-methanesulfonic acid 3-{4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-2-hydroxy-propyl ester (600 mg, 1.33 mmol) in 7 M NH3 in methanol (10 mL) is stirred in a sealed vessel at 80° C. for 16 h. The mixture is diluted with EA and washed with water and brine. The organic extract is dried over MgSO4, filtered and concentrated. The crude product is purified on prep. TLC plates using DCM containing 10% of methanol to give the title compound (242 mg) as a pale yellow resin; LC-MS: tR=0.63 min; [M+1]+=400.93.

Provenance & Evidence