Hydrochloric Acid → HCID 86712660, compound

LiOH.H2O (41.0 mg, 0.960 mmol) was added to a solution of tert-butyl 4-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-methylphenyl)piperidine-1-carboxylate (A42) (0.196 g, 0.320 mmol) in THF (7 mL), water (1.5 mL) and MeOH (1 mL) and the resulting mixture stirred at room temperature for 19 hours. The volatiles were removed in vacuo, then the residue was partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4 and the volatiles removed under reduced pressure. The residue was dissolved in dry THF (6 mL) and dry DMF (1 mL) under an atmosphere of nitrogen then HOBt (0.056 g, 0.41 mmol), EDCl.HCl (0.079 g, 0.41 mmol) and DIPEA (0.28 mL, 1.3 mmol) were added. After 10 minutes ammonium carbonate (0.15 g, 1.6 mmol) was added in one portion and the resulting mixture stirred at room temperature for 19 hours. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (65 mL) and saturated NaHCO3 (65 mL). The aqueous layer was extracted with EtOAc (2×50 mL) then the combined organic layers were washed with brine (50 mL) and dried over MgSO4. The solvent was removed in vacuo and the residue purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-80% EtOAc in petroleum benzine 40-60° C.) to give the title compound A43 as a white solid (0.16 g, 84%); 1H NMR (400 MHz, CDCl3) δ 8.49 (s, 1H), 8.20 (s, 1H), 7.46 (dd, J=8.4, 2.0 Hz, 1H), 7.37 (d, J=1.9 Hz, 1H), 7.28-7.18 (m, obscured by solvent), 7.13 (d, J=8.4 Hz, 1H), 6.33 (s, 1H), 5.68 (s, 1H), 4.40-4.16 (m, 2H), 3.68 (s, 2H), 3.17-2.95 (m, 4H), 2.91-2.68 (m, 3H), 2.34 (s, 3H), 1.73 (d, J=12.3 Hz, 2H), 1.68-1.53 (m, 2H), 1.50 (s, 9H). LCMS-A: rt 6.670 min; m/z 598.1 [M+H]+.

1. customThe volatiles were removed in vacuo
2. customthe residue was partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL)
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
5. washThe combined organic layers were washed with brine (50 mL)
6. dry with materialdried over MgSO4
7. customthe volatiles removed under reduced pressure
8. dissolutionThe residue was dissolved in dry THF (6 mL)
9. stirringthe resulting mixture stirred at room temperature for 19 hours
10. customThe volatiles were removed in vacuo
11. customthe residue was partitioned between EtOAc (65 mL) and saturated NaHCO3 (65 mL)
12. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
13. washthe combined organic layers were washed with brine (50 mL)
14. dry with materialdried over MgSO4
15. customThe solvent was removed in vacuo
16. customthe residue purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-80% EtOAc in petroleum benzine 40-60° C.)

ORD record

ord-94f0398ee2ff41bd90a45a8aaf38d5ea

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266864B2