Orteronel; 6-[(7S)-7-羟基-6,7-二氢-5H-吡咯并[1,2-c]咪唑-7-基]-N-甲基-2-萘甲酰胺合成路线 （共 31 条）
反应条件
1.1: manganese(IV) oxide / dichloromethane / 1.5 h / 20 °C 2.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.5 h / -70 °C / Inert atmosphere 2.2: -70 - -30 °C / Inert atmosphere 2.3: -50 °C / Inert atmosphere 3.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 3 h / -15 - 0 °C 4.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0.5 h / 0 - 10 °C 5.1: acetonitrile / 0.33 h / 70 °C 5.2: 6 h / 70 °C 6.1: n-butyllithium / tetrahydrofuran; hexane / 0.83 h / -78 °C / Inert atmosphere 6.2: 16 h / 0 - 20 °C / Inert atmosphere 6.3: Inert atmosphere 7.1: ethanol 8.1: sodium hydroxide / water View Scheme
参考文献
Bioorganic and Medicinal Chemistry, , vol. 19, # 21 p. 6356 - 6374
反应条件
1.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.5 h / -70 °C / Inert atmosphere 1.2: -70 - -30 °C / Inert atmosphere 1.3: -50 °C / Inert atmosphere 2.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 3 h / -15 - 0 °C 3.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0.5 h / 0 - 10 °C 4.1: acetonitrile / 0.33 h / 70 °C 4.2: 6 h / 70 °C 5.1: n-butyllithium / tetrahydrofuran; hexane / 0.83 h / -78 °C / Inert atmosphere 5.2: 16 h / 0 - 20 °C / Inert atmosphere 5.3: Inert atmosphere 6.1: ethanol 7.1: sodium hydroxide / water View Scheme
参考文献
Bioorganic and Medicinal Chemistry, , vol. 19, # 21 p. 6356 - 6374
反应条件
1.1: n-butyllithium / tetrahydrofuran; hexane / 0.83 h / -78 °C / Inert atmosphere 1.2: 16 h / 0 - 20 °C / Inert atmosphere 1.3: Inert atmosphere 2.1: ethanol 3.1: sodium hydroxide / water View Scheme
参考文献
Bioorganic and Medicinal Chemistry, , vol. 19, # 21 p. 6356 - 6374
反应条件
1.1: triethylamine / acetonitrile / 2.5 h / 70 °C 2.1: 2-(trifluoromethyl)phenyllithium / tetrahydrofuran; hexane / 0.83 h / -65 - -55 °C / Inert atmosphere 2.2: 1.5 h / -65 °C / Inert atmosphere 2.3: Inert atmosphere 3.1: ethanol 4.1: sodium hydroxide / water View Scheme
参考文献
Bioorganic and Medicinal Chemistry, , vol. 19, # 21 p. 6356 - 6374
反应条件
1.1: hydrogen bromide; acetic acid / 2 h / 10 - 20 °C 2.1: triethylamine / acetonitrile / 2.5 h / 70 °C 3.1: 2-(trifluoromethyl)phenyllithium / tetrahydrofuran; hexane / 0.83 h / -65 - -55 °C / Inert atmosphere 3.2: 1.5 h / -65 °C / Inert atmosphere 3.3: Inert atmosphere 4.1: ethanol 5.1: sodium hydroxide / water View Scheme
参考文献
Bioorganic and Medicinal Chemistry, , vol. 19, # 21 p. 6356 - 6374
反应条件
1.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine / tetrahydrofuran; N,N-dimethyl-formamide / 18 h / 0 - 20 °C / Inert atmosphere 2.1: 2-(trifluoromethyl)phenyllithium / tetrahydrofuran; hexane / 0.83 h / -65 - -55 °C / Inert atmosphere 2.2: 1.5 h / -65 °C / Inert atmosphere 2.3: Inert atmosphere 3.1: Chiralpak AD column / ethanol; hexane / Resolution of racemate; HPLC conditions View Scheme
参考文献
Bioorganic and Medicinal Chemistry, , vol. 19, # 21 p. 6356 - 6374
反应条件
1.1: triethylamine / tetrahydrofuran / 1 h / 0 - 20 °C 2.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.83 h / -70 - -60 °C / Inert atmosphere 2.2: 0.67 h / -70 °C / Inert atmosphere 2.3: Inert atmosphere 3.1: manganese(IV) oxide / dichloromethane / 1.5 h / 20 °C 4.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.5 h / -70 °C / Inert atmosphere 4.2: -70 - -30 °C / Inert atmosphere 4.3: -50 °C / Inert atmosphere 5.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 3 h / -15 - 0 °C 6.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0.5 h / 0 - 10 °C 7.1: acetonitrile / 0.33 h / 70 °C 7.2: 6 h / 70 °C 8.1: n-butyllithium / tetrahydrofuran; hexane / 0.83 h / -78 °C / Inert atmosphere 8.2: 16 h / 0 - 20 °C / Inert atmosphere 8.3: Inert atmosphere 9.1: ethanol 10.1: sodium hydroxide / water View Scheme
参考文献
Bioorganic and Medicinal Chemistry, , vol. 19, # 21 p. 6356 - 6374
反应条件
1.1: 2-(trifluoromethyl)phenyllithium / tetrahydrofuran; hexane / 0.83 h / -65 - -55 °C / Inert atmosphere 1.2: 1.5 h / -65 °C / Inert atmosphere 1.3: Inert atmosphere 2.1: ethanol 3.1: sodium hydroxide / water View Scheme
参考文献
Bioorganic and Medicinal Chemistry, , vol. 19, # 21 p. 6356 - 6374
反应条件
1: manganese(IV) oxide / isobutyramide / 7 h / 60 °C 2: pyridine; cinchonine / tetrahydrofuran / 3.5 h / -25 - 0 °C 3: calcium chloride; sodium tetrahydroborate / ethanol; tetrahydrofuran / 6 h / -10 - 5 °C 4: calcium chloride; sodium tetrahydroborate / ethanol; tetrahydrofuran / 21.5 h / -10 - 7 °C 5: N-ethyl-N,N-diisopropylamine; methanesulfonyl chloride; sodium carbonate / tetrahydrofuran / 8 h / 25 °C View Scheme
反应条件
1: pyridine; cinchonine / tetrahydrofuran / 3.5 h / -25 - 0 °C 2: calcium chloride; sodium tetrahydroborate / ethanol; tetrahydrofuran / 6 h / -10 - 5 °C 3: calcium chloride; sodium tetrahydroborate / ethanol; tetrahydrofuran / 21.5 h / -10 - 7 °C 4: N-ethyl-N,N-diisopropylamine; methanesulfonyl chloride; sodium carbonate / tetrahydrofuran / 8 h / 25 °C View Scheme
