Cesium carbonate → methyl 2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-4-fluorobenzoate

Participants

Reaction Conditions

Reaction Steps

To a dried 25 mL flask was introduced 3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-amine (Intermediate C, 110 mg, 0.48 mmol), methyl 2-bromo-4-fluorobenzoate (93.1 mg, 0.40 mmol), Pd2(dba)3 (18.3 mg, 0.02 mmol), BINAP (24.9 mg, 0.04 mmol), and Cs2CO3 (182 mg, 0.56 mmol). The flask was degassed followed by the addition of toluene (1 mL), and the mixture was heated to 110° C. for 20 h. The mixture was then cooled to rt, and diluted with ethyl acetate. The solid was filtered off, and the solvent was removed under reduced pressure. The residue was redissolved in methanol/THF (4:1, v/v) and filtered through a C8-silica plug. HPLC purification using gradient elution from 30% to 90% acetonitrile in water afforded 136.2 mg (89%) of the title compound. 1H NMR (300 MHz, CD2Cl2) δ 9.42 (s, 1H), 7.85 (dd, 1H), 7.21-7.30 (m, 4H), 6.86 (dd, 1H), 6.44 (dt, 1H), 6.11 (s, 1H), 3.70 (s, 3H), 2.04 (s, 3H), 1.30 (s, 9H). ES-MS m/z 381.9 (MH+); HPLC RT (min) 4.50.

Provenance & Evidence