4-[(1E)-2-[5-[(1R)-1-(3,5-二氯-4-吡啶基)乙氧基]-1H-吲唑-3-基]乙烯基]-1H-吡唑-1-乙醇合成路线 （共 9 条）
反应条件
1: With methanol; acetyl chloride T=20°C; 4 h; Cooling with iceInert atmosphere; 2: With sodium hydrogencarbonate in methanol; water T=20°C; 0.5 h;
参考文献
ELI LILLY AND COMPANY
Patent: US2012/83511 A1, 2012 ;
Location in patent: Page/Page column 3 ;
反应条件
1.1: 1H-imidazole / N,N-dimethyl-formamide / 3.5 h / 0 - 18 °C 2.1: N-iodo-succinimide / dichloromethane / 3.5 h / 10 - 20 °C 3.1: methanesulfonic acid / dichloromethane; tetrahydrofuran / 3.5 h / 10 - 20 °C 3.2: 10 °C 4.1: tributyl-amine / bis-triphenylphosphine-palladium(II) chloride / N,N-dimethyl-formamide / 18.67 h / 95 - 100 °C / Inert atmosphere 4.2: 3.67 h / 40 - 95 °C / Inert atmosphere 5.1: caesium carbonate / acetonitrile / 60 °C / Inert atmosphere 6.1: acetyl chloride; methanol / 4 h / 20 °C / Inert atmosphere; Cooling with ice 6.2: 0.5 h / 20 °C View Scheme
反应条件
1.1: tributyl-amine / bis-triphenylphosphine-palladium(II) chloride / N,N-dimethyl-formamide / 18.67 h / 95 - 100 °C / Inert atmosphere 1.2: 3.67 h / 40 - 95 °C / Inert atmosphere 2.1: caesium carbonate / acetonitrile / 60 °C / Inert atmosphere 3.1: acetyl chloride; methanol / 4 h / 20 °C / Inert atmosphere; Cooling with ice 3.2: 0.5 h / 20 °C View Scheme
反应条件
1.1: N-iodo-succinimide / dichloromethane / 3.5 h / 10 - 20 °C 2.1: methanesulfonic acid / dichloromethane; tetrahydrofuran / 3.5 h / 10 - 20 °C 2.2: 10 °C 3.1: tributyl-amine / bis-triphenylphosphine-palladium(II) chloride / N,N-dimethyl-formamide / 18.67 h / 95 - 100 °C / Inert atmosphere 3.2: 3.67 h / 40 - 95 °C / Inert atmosphere 4.1: caesium carbonate / acetonitrile / 60 °C / Inert atmosphere 5.1: acetyl chloride; methanol / 4 h / 20 °C / Inert atmosphere; Cooling with ice 5.2: 0.5 h / 20 °C View Scheme
反应条件
1.1: methanesulfonic acid / dichloromethane; tetrahydrofuran / 3.5 h / 10 - 20 °C 1.2: 10 °C 2.1: tributyl-amine / bis-triphenylphosphine-palladium(II) chloride / N,N-dimethyl-formamide / 18.67 h / 95 - 100 °C / Inert atmosphere 2.2: 3.67 h / 40 - 95 °C / Inert atmosphere 3.1: caesium carbonate / acetonitrile / 60 °C / Inert atmosphere 4.1: acetyl chloride; methanol / 4 h / 20 °C / Inert atmosphere; Cooling with ice 4.2: 0.5 h / 20 °C View Scheme
反应条件
1.1: tributyl-amine / bis-triphenylphosphine-palladium(II) chloride / N,N-dimethyl-formamide / 18.67 h / 95 - 100 °C / Inert atmosphere 1.2: 3.67 h / 40 - 95 °C / Inert atmosphere 2.1: caesium carbonate / acetonitrile / 60 °C / Inert atmosphere 3.1: acetyl chloride; methanol / 4 h / 20 °C / Inert atmosphere; Cooling with ice 3.2: 0.5 h / 20 °C View Scheme
反应条件
1.1: N-ethyl-N,N-diisopropylamine; n-butyllithium / hexane; tetrahydrofuran / 3 h / -78 °C 1.2: -78 - 20 °C 2.1: CHIRALPAK AD-H column / n-heptane; ethanol / Resolution of racemate 3.1: triethylamine / dichloromethane / 4 h / 20 °C / Cooling with ice 4.1: caesium carbonate / acetonitrile / 60 °C / Inert atmosphere 5.1: acetyl chloride; methanol / 4 h / 20 °C / Inert atmosphere; Cooling with ice 5.2: 0.5 h / 20 °C View Scheme
反应条件
1.1: CHIRALPAK AD-H column / n-heptane; ethanol / Resolution of racemate 2.1: triethylamine / dichloromethane / 4 h / 20 °C / Cooling with ice 3.1: caesium carbonate / acetonitrile / 60 °C / Inert atmosphere 4.1: acetyl chloride; methanol / 4 h / 20 °C / Inert atmosphere; Cooling with ice 4.2: 0.5 h / 20 °C View Scheme
反应条件
1.1: triethylamine / dichloromethane / 4 h / 20 °C / Cooling with ice 2.1: caesium carbonate / acetonitrile / 60 °C / Inert atmosphere 3.1: acetyl chloride; methanol / 4 h / 20 °C / Inert atmosphere; Cooling with ice 3.2: 0.5 h / 20 °C View Scheme
