p-Toluenesulfonic acid → HCID 13520534, compound

Participants

Reaction Steps

To a mixture of (S)-1-[(S)-3-(benzoylthio)-2-methyl-1-oxopropyl]-4-[4-(2-methoxyethenyl)phenoxy]-L-proline, diphenylmethyl ester (3.6 g., 5.66 mmole), 4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (1.8 g., 5.7 mmole) and anisole (3.5 ml.) in 80 ml. of acetonitrile is added 120 mg. of p-toluenesulfonic acid. The reaction is essentially complete after refluxing for one hour. The solvent is removed under vacuum and the residue is triturated with diethyl ether to give a solid. The solid is purified by chromatography on an LPS-1 column eluted with ethyl acetate:pyridine:acetic acid:water (2400:50:15:27). After removal of the solvents on a rotary film evaporator using benzene to azeotrope off the acetic acid and pyridine, 3.8 g. of a homogeneous solid is obtained. Approximately half this material is passed through an LH-20 column (methanol) to give an analytically pure sample of (S)-4-[4-[[7-(aminosulfonyl)-3,4-dihydro-1,1-dioxo-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazin-3-yl]methyl]phenoxy]-1-[(S)-3-(benzoylthio)-2-methyl-1-oxopropyl]-L-proline; m.p. 170°-182° (foams); [α]D =-24.6° (c=1.0%, methanol). TLC (silica, methylene chloride:methanol:acetic acid; 8:1:1) Rf =0.47.

Provenance & Evidence