2-Chlorobenzoic Acid → HCID 19783221, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 675 mg (4.28 mmol) of 2-chlorobenzoic acid, 695 mg (4.28 mmol) of 1,1'-carbonyldiimidazole (CDI), and 2 mL of dry THF was stirred at 50° C. under N2 for 3 hours. Then a solution of 851 mg (1.43 mmol) of ethyl 3-n-butyl-1-(2-chloro-5-nitrophenyl)-4-[(2'-sulfamoylbiphenyl-4-yl)methyl]-1H-pyrazole-5-carboxylate (from Step G) and 640 μL (651 mg, 4.28 mmol) of 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU) in 5 mL of dry THF was added, and stirring under N2 at 50° C. was continued overnight. The cooled reaction mixture was partitioned between 75 mL of 5% citric acid (aqueous) and 75 mL of ethyl acetate. The organic phase was washed with H2O, dried (Na2SO4), filtered, and concentrated. The orange residue was flash chromatographed on silica gel (elution with 1% MeOH in CH2Cl2) to yield 503 mg (48%) of the title compound as a solid, mp>60° C. (gradual); homogeneous by TLC in 95:5 CH2Cl2 --MeOH; mass spectrum (FAB) m/e 736 (M+1)+. 400 MHz 1H NMR (CDCl3) δ0.88 (t, J=7.3 Hz, 3H), 1.05 (t, J=7.1 Hz, 3H), 1.34 (m, 2H), 1.59 (m, 2H, partially obscured by H2O peak), 2.56 (t, J=7.8 Hz, 2H), 4.14 (q, J=7.1 Hz, 2H), overlapping 4.16 (s, 2H), 7.07 (d, J=8.1 Hz, 2H), 7.25-7.45 (m, 6H), 7.55-7.69 (m, 4H), 8.26 (dd, J=8.8, 2.6 Hz, 1H), 8.35 (dd, J=8.1, 1.3 Hz, 2H).

Provenance & Evidence