反应详情

温度

60 °C

2,6-difluoro-4-methoxybenzoic acid (22.6 mg, 120 μmol) was weighed into a microwave vial and CH2Cl2 (1 mL) was added followed by HATU (34.3 mg, 90.3 μmol) and Et3N (20 μl, 144 μmol). After stirring 10 minutes, tert-butyl 2-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)ethylcarbamate (20 mg, 60 μmol) was added to the solution. The reaction mixture was heated at 60° C. for one hour. Then, TFA (1 mL) was added and heated for one hour at 90° C. in order to remove the Boc-protecting group from the amine. The solvent was evaporated. The resulting oil was dissolved in DMSO (1 mL) and purified by Prep LC/MS to give N-[4-(2-amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-2,6-difluoro-4-methoxy-benzamide trifluoroacetate (8.2 mg, 0.02 mmol, 34%) as a white solid. LCMS m/z (%)=403 (M+H). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.16 (s, 2H), 3.70 (s, 3H), 3.84 (s, 3H), 4.17 (t, J=5.56 Hz, 2H), 6.36 (d, J=1.77 Hz, 1H), 6.89 (d, J=9.85 Hz, 1H), 7.24 (d, J=9.09 Hz, 1H), 7.49 (d, J=1.77 Hz, 1H), 7.63 (d, J=2.78 Hz, 1H), 7.77 (dd, J=9.09, 2.53 Hz, 1H), 7.89 (br. s., 3H), 10.69 (s, 1H), 13.46 (s, 1H).

1. additionwas added
2. temperatureheated for one hour at 90° C. in order
3. customto remove the Boc-
4. customThe solvent was evaporated
5. dissolutionThe resulting oil was dissolved in DMSO (1 mL)
6. custompurified by Prep LC/MS