Hydrochloric Acid → Hydrochloric Acid

温度

100 °C

A 25 mL round bottom flask was charged with 2-chloro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (74 mg, 0.282 mmol), 1-(3-bromo-5-fluoro-pyridin-4-yl)-2-ethoxy-ethanol (62 mg, 0.235 mmol), 2M aqueous sodium carbonate (0.235 mL, 0.470 mmol) and DMF (5 mL). The reaction mixture was evacuated and flushed with N2 twice, followed by addition of PdCl2(dppf). CH2Cl2 adduct (9.6 mg, 0.012 mmol). The reaction was stirred under N2 at 100° C. for 30 min. The reaction mixture was cooled to room temperature diluted with ethyl acetate and washed with water twice. The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude was dissolved in DMF (5 mL) and purified by HPLC using an Xbridge Shield RP18 column and gradient 0.1% aqueous NH4OH in acetonitrile to afford a solid, which was dissolved in DCM (2 mL) and 4N HCl in dioxane (0.5 mL). The solvents were evaporated and the product was lyophilized to afford the product 2-chloro-4-[4-(2-ethoxy-1-hydroxy-ethyl)-5-fluoro-pyridin-3-yl]-benzonitrile as an HCl salt. 1H NMR (400 MHz, MeOD, HCl salt) δ ppm 1.17 (t, J=6.9 Hz, 3H), 3.46-3.57 (m, 2H), 3.81 (dd, J=6.7, 1.4 Hz, 2H), 4.90 (t, J=6.8 Hz, 1H), 7.61 (dd, J=8.0, 1.6 Hz, 1H), 7.86 (d, J=1.5 Hz, 1H), 7.96 (d, J=8.1 Hz, 1H), 8.36 (s, 1H), 8.60 (d, J=2.8 Hz, 1H); HRMS: (ESI) m/z 321.0801 [(M+H)+ Calcd for C16H14ClFN2O2 321.0806].

1. customThe reaction mixture was evacuated
2. customflushed with N2 twice
3. additionfollowed by addition of PdCl2(dppf)
4. temperatureThe reaction mixture was cooled to room temperature
5. washwashed with water twice
6. dry with materialThe organic layer was dried over sodium sulfate
7. concentrationconcentrated in vacuo
8. dissolutionThe crude was dissolved in DMF (5 mL)
9. custompurified by HPLC
10. customto afford a solid, which
11. customThe solvents were evaporated

ORDレコード

ord-7781022fe5da4ac181465ebf8868a592

出典データセット

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08519134B2