反应详情

TFA (921 μl, 11.9 mmol) was added to a stirring solution of tert-butyl 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)benzoate (130 mg, 0.239 mmol) in DCM (2.4 ml) at rt. The reaction was allowed to stir for 2 h then concentrated azeotroping with toluene to dryness. The resulting solid was triturated with DCM to give the expected product 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)benzoic acid (97 mg, 0.20 mmol, 83% yield) consistent by LCMS and NMR. LC-MS retention time: 1.73 min; m/z (MH+): 488. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 3u C18 2.0×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 1 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode. 1H NMR (400 MHz, DMSO-d6) δ 13.07 (br. s, 1H), 8.37-8.30 (m, J=4.5 Hz, 1H), 8.05-7.94 (m, 4H), 7.70-7.66 (m, 3H), 7.34 (t, J=8.9 Hz, 2H), 6.67 (s, 1H), 4.23-4.10 (m, J=3.0 Hz, 2H), 2.80 (d, J=4.8 Hz, 3H).

1. concentrationthen concentrated
2. customazeotroping with toluene to dryness
3. customThe resulting solid was triturated with DCM