Hydrochloric Acid → 4-{3-[2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-benzoic acid

Participants

Reaction Conditions

Reaction Steps

The 4-{3-[2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-benzoic acid methyl ester (prepared in example 44, 840 mg, 1.54 mmol) was dissolved in dioxane (20 mL) and 6.0 M aqueous hydrochloric acid (20 mL) was added. The reaction was heated to 80° C. in a sealed vial while stirring for 8 h. Upon cooling, the reaction was diluted with water (25 mL) and the product extracted into ethyl acetate (3×50 mL). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to give the desired product, 4-{3-[2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-benzoic acid (328 mg, 40%) as a white powder: ESI-LRMS m/e calcd for C26H28ClN3O5S [M+] 529.1, found 530.2 [M+H+]; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.01-1.13 (m, 2H, CH2), 1.33-1.80 (m, 8H, 4×CH2), 1.94-2.19 (m, 1H, CH), 3.32 (s, 3 H, SO2CH3), 3.83-3.93 (m, 1H, CH), 5.26 (s, 2H, NCH2), 6.47 (d, J=2.2 Hz, 1H, Ar), 7.26 (d, Jo=8.4 Hz, 2H, Ar), 7.55 (dd, Jo=8.2, Jm=1.7 Hz. 1H, Ar), 7.65 (d, Jm=1.7 Hz, 1H, Ar), 7.74 (d, J=2.2 Hz, 1H, Ar), 7.87 (d, Jo=8.4 Hz, 2H, Ar), 7.97 (d, Jo=8.2 Hz, 1H, Ar), 10.78 (s, 1H, NH), 12.88 (br.s., 1H, CO2H).

Provenance & Evidence