1,2-Cyclopropanedicarboxylic acid, trans- → trans-2-(4-(2,6-Dichlorobenzamido)pyridin-2-ylcarbamoyl)cyclopropanecarboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of N-(2-aminopyridin-4-yl)-2,6-dichlorobenzamide (141 mg, 0.50 mmol), trans-cyclopropane-1,2-dicarboxylic acid (325 mg, 2.5 mmol), and disiopropylethylamine (339 mg, 2.63 mmol) in dry DMF (5 mL) was added HATU (1951 mg, 2.5 mmol). The reaction mixture was heated at 70° C. for 6 hours and then quenched with sat. NH4Cl (100 mL). The mixture was extracted with EtOAc (3×100 mL). The combined organic extracts were dried with Na2SO4 and concentrated under reduced pressure. The residue was purified by prep HPLC (10-50% CH3CN/H2O with 0.1% formic acid) to give trans-2-(4-(2,6-dichlorobenzamido)pyridin-2-ylcarbamoyl)cyclopropanecarboxylic acid (132 mg, 67% yield). 1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 10.86 (s, 1H), 8.38 (s, 1H), 8.23 (d, J=5.6 Hz, 1H), 7.62-7.55 (m, 2H), 7.54-7.45 (m, 2H), 1.90-1.82 (m, 1H), 1.25 (dt, J=8.0, 5.4 Hz, 3H). LCMS (ESI) m/z: 394.0 [M+H+].

Provenance & Evidence