(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
trifluoroacetic acid in dichloromethane
T=20°C; 2 h;
参考文献
Pfizer Inc
Patent: US6350907 B1, 2002 ;
Location in patent: Example 14 ;
反应条件
1.1: Mg; I2 / tetrahydrofuran / Heating
1.2: 60 percent / tetrahydrofuran / -40 - 0 °C
2.1: Et3SiH; TFA / 0 - 20 °C
3.1: (COCl)2; DMF / CH2Cl2 / -10 - 20 °C
4.1: n-BuLi / tetrahydrofuran; hexane / 0.5 h / -70 - -50 °C
4.2: 91 percent / tetrahydrofuran; hexane / -70 - 0 °C
5.1: NaN(SiMe3)2 / tetrahydrofuran / 1 h / -75 °C
5.2: 61 percent / tetrahydrofuran / -70 - -50 °C
6.1: 97 percent / aq. H2O2; LiOH / tetrahydrofuran / 0 - 20 °C
7.1: 99 percent / N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride; i-Pr2NEt; 1-hydroxy-1,2,3-benzotriazole hydrate / CH2Cl2 / 4 - 20 °C
8.1: 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
1.1: 79 percent / Pd(OAc)2; PPh3; aq. Na2CO3 / acetone / 18 h / Heating
2.1: Mg; I2 / tetrahydrofuran / Heating
2.2: 60 percent / tetrahydrofuran / -40 - 0 °C
3.1: Et3SiH; TFA / 0 - 20 °C
4.1: (COCl)2; DMF / CH2Cl2 / -10 - 20 °C
5.1: n-BuLi / tetrahydrofuran; hexane / 0.5 h / -70 - -50 °C
5.2: 91 percent / tetrahydrofuran; hexane / -70 - 0 °C
6.1: NaN(SiMe3)2 / tetrahydrofuran / 1 h / -75 °C
6.2: 61 percent / tetrahydrofuran / -70 - -50 °C
7.1: 97 percent / aq. H2O2; LiOH / tetrahydrofuran / 0 - 20 °C
8.1: 99 percent / N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride; i-Pr2NEt; 1-hydroxy-1,2,3-benzotriazole hydrate / CH2Cl2 / 4 - 20 °C
9.1: 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: 81 percent / N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride; N-methylmorpholine; 1-hydroxy-1,2,3-benzotriazole hydrate / CH2Cl2 / 2 - 20 °C
2: 97 percent / HCl(gas) / CH2Cl2; dioxane / 4 - 20 °C
3: 99 percent / N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride; i-Pr2NEt; 1-hydroxy-1,2,3-benzotriazole hydrate / CH2Cl2 / 4 - 20 °C
4: 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: 81 percent / N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride; N-methylmorpholine; 1-hydroxy-1,2,3-benzotriazole hydrate / CH2Cl2 / 2 - 20 °C
2: 97 percent / HCl(gas) / CH2Cl2; dioxane / 4 - 20 °C
3: 99 percent / N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride; i-Pr2NEt; 1-hydroxy-1,2,3-benzotriazole hydrate / CH2Cl2 / 4 - 20 °C
4: 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 / HCl(gas) / CH2Cl2; dioxane / 4 - 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
1.1: sodium carbonate / palladium diacetate; triphenylphosphine / water; acetone / 18 h / Heating / reflux
2.1: iodine; magnesium / tetrahydrofuran / 1 h / Heating / reflux
3.1: tetrahydrofuran / 1.5 h / -40 °C
3.2: 0 °C
4.1: triethylsilane / trifluoroacetic acid / 2 h / 0 - 20 °C
5.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 5 h / -10 - 20 °C
6.1: tetrahydrofuran; hexane / 1.25 h / -70 °C
7.1: sodium hexamethyldisilazide / tetrahydrofuran / 1 h / -75 °C
7.2: 2.33 h / -70 °C
8.1: lithium hydroxide; dihydrogen peroxide / tetrahydrofuran; water / 3 h / 0 - 20 °C
8.2: pH 6
9.1: benzotriazol-1-ol; N'-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine / dichloromethane / 19 h / 4 - 20 °C
10.1: 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: Mg; I2 / tetrahydrofuran / Heating
1.2: 60 percent / tetrahydrofuran / -40 - 0 °C
2.1: Et3SiH; TFA / 0 - 20 °C
3.1: (COCl)2; DMF / CH2Cl2 / -10 - 20 °C
4.1: n-BuLi / tetrahydrofuran; hexane / 0.5 h / -70 - -50 °C
4.2: 91 percent / tetrahydrofuran; hexane / -70 - 0 °C
5.1: NaN(SiMe3)2 / tetrahydrofuran / 1 h / -75 °C
5.2: 61 percent / tetrahydrofuran / -70 - -50 °C
6.1: 97 percent / aq. H2O2; LiOH / tetrahydrofuran / 0 - 20 °C
7.1: 99 percent / N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride; i-Pr2NEt; 1-hydroxy-1,2,3-benzotriazole hydrate / CH2Cl2 / 4 - 20 °C
8.1: 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
1.1: (COCl)2; DMF / CH2Cl2 / -10 - 20 °C
2.1: n-BuLi / tetrahydrofuran; hexane / 0.5 h / -70 - -50 °C
2.2: 91 percent / tetrahydrofuran; hexane / -70 - 0 °C
3.1: NaN(SiMe3)2 / tetrahydrofuran / 1 h / -75 °C
3.2: 61 percent / tetrahydrofuran / -70 - -50 °C
4.1: 97 percent / aq. H2O2; LiOH / tetrahydrofuran / 0 - 20 °C
5.1: 99 percent / N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride; i-Pr2NEt; 1-hydroxy-1,2,3-benzotriazole hydrate / CH2Cl2 / 4 - 20 °C
6.1: 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
1.1: Et3SiH; TFA / 0 - 20 °C
2.1: (COCl)2; DMF / CH2Cl2 / -10 - 20 °C
3.1: n-BuLi / tetrahydrofuran; hexane / 0.5 h / -70 - -50 °C
3.2: 91 percent / tetrahydrofuran; hexane / -70 - 0 °C
4.1: NaN(SiMe3)2 / tetrahydrofuran / 1 h / -75 °C
4.2: 61 percent / tetrahydrofuran / -70 - -50 °C
5.1: 97 percent / aq. H2O2; LiOH / tetrahydrofuran / 0 - 20 °C
6.1: 99 percent / N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride; i-Pr2NEt; 1-hydroxy-1,2,3-benzotriazole hydrate / CH2Cl2 / 4 - 20 °C
7.1: 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
