Hydrochloric Acid → HCID 86712651, compound

LiOH.H2O (0.063 g, 1.5 mmol) was added to a solution of tert-butyl 4-(2-fluoro-4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A31) (0.30 g, 0.49 mmol) in THF (10 mL), water (2 mL) and MeOH (1.5 mL) and the resulting mixture was stirred at room temperature for 18 hours. The volatiles were removed in vacuo and 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 (MgSO4) and the volatiles removed in vacuo to give a white solid. The solid was dissolved in dry THF (12 mL) and dry DMF (2 mL) under an atmosphere of nitrogen and HOBt (0.086 g, 0.64 mmol), EDCl.HCl (0.12 g, 0.64 mmol) and DIPEA (0.43 mL, 2.4 mmol) were added. After 10 minutes ammonium carbonate (0.24 g, 2.4 mmol) was added in one portion and the resulting mixture was stirred at room temperature for 18 hours. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (65 mL) and saturated aqueous 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 volatiles were removed in vacuo to afford a pale yellow oil which was purified by silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-80% EtOAc in petroleum benzine 40-60° C.) to give the title compound A32 as a white solid (0.209 g, 69%); 1H NMR (400 MHz, CDCl3) δ 8.50 (s, 1H), 8.44 (s, 1H), 7.61 (dd, J=12.8, 2.2 Hz, 1H), 7.30-7.18 (m, 5H), 7.09 (t, J=8.4 Hz, 1H), 6.31 (s, 1H), 5.69 (s, 1H), 4.39-4.16 (m, 2H), 3.72 (s, 2H), 3.14-3.00 (m, 4H), 2.94 (tt, J=12.1, 3.3 Hz, 1H), 2.81 (t, J=11.4 Hz, 2H), 1.78 (d, J=12.2 Hz, 2H), 1.69-1.53 (m, 2H), 1.49 (s, 9H). LCMS-A: rt 6.710 min; m/z 602.3 [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 (MgSO4)
7. customthe volatiles removed in vacuo
8. customto give a white solid
9. stirringthe resulting mixture was stirred at room temperature for 18 hours
10. customThe volatiles were removed in vacuo
11. customthe residue was partitioned between EtOAc (65 mL) and saturated aqueous 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 volatiles were removed in vacuo
16. customto afford a pale yellow oil which
17. customwas purified by silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-80% EtOAc in petroleum benzine 40-60° C.)

ORD record

ord-b77ad7803a5d4715a5107c61d8c164c5

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266864B2