Dicyclohexylcarbodiimide → (1R,2S)-2-{(4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclopentanecarboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

(1R,2S)-2-(4-Fluoro-benzylamino)-cyclopentanecarboxylic acid methyl ester (106 mg, 0.42 mmol) and (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1j, 140 mg, 0.42 mmol) were dissolved in a 1:1 mixture of dichloromethane and N,N′-dimethylformamide (6 mL). A 1.0 M solution of N,N′-dicyclohexylcarbodiimide in dichloromethane (0.46 mL, 0.46 mmol) was added. The reaction was stirred at 25° C. for 16 h. The mixture was concentrated in vacuo and purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 0-85% ethyl acetate in hexanes) to afford the desired product, (1R,2S)-2-{(4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclopentanecarboxylic acid methyl ester (127 mg, 0.22 mmol, 52%), as a white solid. 1H NMR (400 MHz, CDCl3) δ: 1.80-2.22 (6H, m), 3.07 (3H, s), 3.24 (1H, dd, J1=18.8 Hz, J2=8.0 Hz), 3.32 (1H, dd, J1=15.6 Hz, J2=8.0 Hz), 3.69 (1H, s), 4.63 (2H, d, J=4.8 Hz), 4.67-4.74 (1H, m), 4.82-4.89 (1H, m), 6.99-7.14 (5H, m), 7.51-7.64 (2H, m). LC-MS (ESI) calcd for C24H27FN4O7S2 566.62, found 567.1 [M+H+].

Provenance & Evidence