(R)-3-((s)-1-((s)-2-甲氧基-1-苯基乙基氨基)-3,3-二甲基-1-氧代-2-丁基氨基甲酰)-6-(2-甲基联苯-4-基)己酸合成路线 （共 18 条）
反应条件
1: 99 percent / N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride; i-Pr2NEt; 1-hydroxy-1,2,3-benzotriazole hydrate / CH2Cl2 / 4 - 20 °C
2: 80 percent / TFA / CH2Cl2 / 2 h / 20 °C
View Scheme
参考文献
Fray, M. Jonathan; Dickinson, Roger P.; Huggins, John P.; Occleston, Nicholas L.
Journal of Medicinal Chemistry, 2003 , vol. 46, # 16 p. 3514 - 3525
反应条件
1.1: NaN(SiMe3)2 / tetrahydrofuran / 1 h / -75 °C
1.2: 61 percent / tetrahydrofuran / -70 - -50 °C
2.1: 97 percent / aq. H2O2; LiOH / tetrahydrofuran / 0 - 20 °C
3.1: 99 percent / N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride; i-Pr2NEt; 1-hydroxy-1,2,3-benzotriazole hydrate / CH2Cl2 / 4 - 20 °C
4.1: 80 percent / TFA / CH2Cl2 / 2 h / 20 °C
View Scheme
参考文献
Fray, M. Jonathan; Dickinson, Roger P.; Huggins, John P.; Occleston, Nicholas L.
Journal of Medicinal Chemistry, 2003 , vol. 46, # 16 p. 3514 - 3525
反应条件
1: 97 percent / aq. H2O2; LiOH / tetrahydrofuran / 0 - 20 °C
2: 99 percent / N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride; i-Pr2NEt; 1-hydroxy-1,2,3-benzotriazole hydrate / CH2Cl2 / 4 - 20 °C
3: 80 percent / TFA / CH2Cl2 / 2 h / 20 °C
View Scheme
参考文献
Fray, M. Jonathan; Dickinson, Roger P.; Huggins, John P.; Occleston, Nicholas L.
Journal of Medicinal Chemistry, 2003 , vol. 46, # 16 p. 3514 - 3525
反应条件
1: n-ethyl morpholine / acetonitrile / 16.5 h / Heating / reflux
2: hydrogen / palladium 10 on activated carbon / ethanol; water / 6 h / 20 °C / 2250.23 Torr
3: PyAOP / dichloromethane / 3.75 h / 0 - 20 °C
4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C
View Scheme
参考文献
Pfizer Inc
Patent: US6350907 B1, 2002 ;
反应条件
1: 4-methyl-morpholine; benzotriazol-1-ol; N'-(3-dimethylaminopropyl)-N-ethylcarbodiimide / dichloromethane / 20 h / 0 - 20 °C
2: n-ethyl morpholine / acetonitrile / 16.5 h / Heating / reflux
3: hydrogen / palladium 10 on activated carbon / ethanol; water / 6 h / 20 °C / 2250.23 Torr
4: PyAOP / dichloromethane / 3.75 h / 0 - 20 °C
5: trifluoroacetic acid / dichloromethane / 2 h / 20 °C
View Scheme
参考文献
Pfizer Inc
Patent: US6350907 B1, 2002 ;
反应条件
1.1: [RuCl(p-cumene)((S)-2,2-bis(diphenylphosphino)-1,1-binaphthyl)]chloride; hydrogen / methanol / 40 h / 60 °C / 3102.97 Torr
1.2: 16 h / 20 - 40 °C
2.1: citric acid / dichloromethane; water
3.1: N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / dichloromethane / 0 - 20 °C
4.1: trifluoroacetic acid / dichloromethane / 16.25 h / 20 - 25 °C / |Inert atmosphere
View Scheme
参考文献
Ashcroft, Christopher P.; Challenger, Stephen; Derrick, Andrew M.; Storey, Richard; Thomson, Nicholas M.
Organic Process Research and Development, 2003 , vol. 7, # 3 p. 362 - 368
反应条件
1: N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / dichloromethane / 0 - 20 °C
2: trifluoroacetic acid / dichloromethane / 16.25 h / 20 - 25 °C / |Inert atmosphere
View Scheme
参考文献
Ashcroft, Christopher P.; Challenger, Stephen; Derrick, Andrew M.; Storey, Richard; Thomson, Nicholas M.
Organic Process Research and Development, 2003 , vol. 7, # 3 p. 362 - 368
反应条件
1: PyAOP / dichloromethane / 3.75 h / 0 - 20 °C
2: trifluoroacetic acid / dichloromethane / 2 h / 20 °C
View Scheme
参考文献
Pfizer Inc
Patent: US6350907 B1, 2002 ;
