反应详情

HOBt (50 mg, 0.37 mmol), EDCl.HCl (78 mg, 0.41 mmol) and DIPEA (0.11 mL, 0.63 mmol) were added to a stirred solution of 2-(2-(2-(2-((6-(1-(tert-butoxycarbonyl)piperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid (A46) (74 mg, 0.13 mmol) in dry DMF (5 mL) under an atmosphere of nitrogen. After 10 minutes ammonium carbonate (121 mg, 1.26 mmol) was added in one portion and the resulting mixture was stirred for 18 hours at room temperature. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (10 mL) and saturated aqueous NaHCO3 (10 mL). The aqueous layer was extracted with EtOAc (2×10 mL) then the combined organic layers were washed with brine (10 mL) and dried over Na2SO4. The volatiles were removed in vacuo and the residue purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridges, 0-100% EtOAc in petroleum benzine 40-60° C. followed by 0-25% MeOH in EtOAc) to give the title compound A47 as clear oil (58 mg, 78%); 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H), 8.54 (s, 1H), 7.97 (s, 1H), 7.80 (s, 1H), 7.30-7.22 (m, 4H), 7.17 (d, J=8.5 Hz, 1H), 5.78 (s, 1H), 5.62 (s, 1H), 4.25 (s, 2H), 3.74 (s, 2H), 3.11 (s, 4H), 2.83 (m, 3H), 1.92 (d, J=12.3 Hz, 2H), 1.79-1.60 (m, 2H, peak obscured), 1.48 (s, 9H). LCMS-A: rt 5.549 min; m/z 585 [M+H]+.

1. customThe volatiles were removed in vacuo
2. customthe residue was partitioned between EtOAc (10 mL) and saturated aqueous NaHCO3 (10 mL)
3. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
4. washthe combined organic layers were washed with brine (10 mL)
5. dry with materialdried over Na2SO4
6. customThe volatiles were removed in vacuo
7. customthe residue purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridges, 0-100% EtOAc in petroleum benzine 40-60° C. followed by 0-25% MeOH in EtOAc)