Trifluoroacetic acid → HCID 60164585, compound

Temperature

35 °C

tert-Butyl 3-(2-(2-((4-(4-methylpiperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)benzoate (I21) (0.025 g, 0.046 mmol) was dissolved in dry DCM (3 mL) under an atmosphere of nitrogen. Trifluoroacetic acid (0.177 mL, 2.31 mmol) was added to the solution and the reaction was stirred at 35° C. for 2 hours. The mixture was concentrated to dryness, toluene (˜2 mL) was added to the residue and the solvent was removed in vacuo to give a yellow solid. This material was dissolved in dry THF (3 mL) and dry DMF (0.2 mL) under an atmosphere of nitrogen. To the solution were added 1-hydroxybenzotriazole (0.009 g, 0.064 mmol) and EDCl (0.012 g, 0.064 mmol) and N,N-diisopropylethylamine (0.048 mL, 0.276 mmol) and the reaction mixture was stirred at room temperature for 10 minutes. Ammonium carbonate (0.018 g, 0.18 mmol) was added in one portion, and the reaction was stirred room temperature for 20 hours. The volatiles were removed in vacuo and the residual solution was diluted with EtOAc (20 mL) and saturated aq. NaHCO3 (10 mL). The layers were separated and the organic layer was washed with water (10 mL), brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo to give a pale yellow solid. The product was dissolved in DCM (˜4 mL) and MeOH (˜1 mL) and the solvents were removed in vacuo. The process was repeated 3 times with DCM only and to give the title compound (2) (0.017 g, 76% yield over 2 steps) as a pale yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 9.97 (s, 1H), 8.60 (s, 1H), 7.95 (br s, 1H), 7.79 (s, 1H), 7.75-7.66 (m, 1H), 7.57-7.47 (m, 2H), 7.40-7.30 (m, 3H), 6.94-6.86 (m, 2H), 3.14-3.01 (m, 8H), 2.47-2.42 (m, 4H), 2.21 (s, 3H). LCMS Method C: rt 4.75 min; m/z 485.3 [M+H]+.

1. concentrationThe mixture was concentrated to dryness, toluene (˜2 mL)
2. additionwas added to the residue
3. customthe solvent was removed in vacuo
4. customto give a yellow solid
5. stirringthe reaction mixture was stirred at room temperature for 10 minutes
6. stirringthe reaction was stirred room temperature for 20 hours
7. customThe volatiles were removed in vacuo
8. additionthe residual solution was diluted with EtOAc (20 mL) and saturated aq. NaHCO3 (10 mL)
9. customThe layers were separated
10. washthe organic layer was washed with water (10 mL), brine (10 mL)
11. dry with materialdried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customto give a pale yellow solid
15. customMeOH (˜1 mL) and the solvents were removed in vacuo

ORD record

ord-ee8686ad80be48c4b0d6e4a1d6d19621

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09421205B2