N-[4-(4-氟苯基)-5-[(1E)-3-羟基-1-丙烯-1-基]-6-(1-甲基乙基)-2-嘧啶基]-N-甲基-甲烷磺酰胺合成路线 （共 12 条）
反应条件
1: 4,4,5,5-tetramethyl-2-[3-(tetrahydro-2H-pyran-2-yloxy)prop-(1E)-enyl]-1,3,2-dioxaborolane With potassium carbonate; 1,1'-bis(di-tert-butylphosphino)ferrocene palladium dichloride in water; acetonitrile
T=20°C; 0.0833333 h;
2: N-(5-bromo-4-(4-fluorophenyl)-6-isopropylpyriinidin-2-yl)-N-methylmethanesulfonamide in water; acetonitrile
T=77°C; 5 h; Heating / reflux;
3: With water; sodium hydrogencarbonate; hydrogenchloride
more than 3 stages;
参考文献
ASTRAZENECA UK LIMITED
Patent: WO2007/7119 A1, 2007 ;
Location in patent: Page/Page column 26-27 ;
WO 2007/007119 A1
反应条件
1: With diisobutylaluminium hydride in toluene
T=-78 - -70°C;
2: With hydrogenchloride in water; toluene
参考文献
Dandala, Ramesh; Mallela, Sambhu Prasad Sarma; Garimella, Narayan K.A.S.S.; Nandi, Sukumar; Buridipad, Sunil Kumar; Nangi, Gangadhar Bhima Shankar; Meenakshisunderam, Sivakumaran
Patent: US2010/48899 A1, 2010 ;
Location in patent: Page/Page column 11 ;
反应条件
sodium hydrogencarbonate; Aliquatreg; 336 in water
T=100°C; 1 h;
参考文献
LEK Pharmaceuticals d.d.
Patent: EP2423195 A1, 2012 ;
Location in patent: Page/Page column 55 ;
反应条件
1,4-diaza-bicyclo[2.2.2]octane in 1,4-dioxane
T=40°C; 24 h;
参考文献
LEK Pharmaceuticals d.d.
Patent: EP2423195 A1, 2012 ;
Location in patent: Page/Page column 54 ;
反应条件
1: With lithium aluminium tetrahydride in tetrahydrofuran
T=-50 - 20°C; 0.75 h;
2: With hydrogenchloride in tetrahydrofuran; water
Product distribution / selectivity;
参考文献
Dandala, Ramesh; Mallela, Sambhu Prasad Sarma; Nandi, Sukumar; Nangi, Gangadhar Bhima Shankar; Buridipadu, Sunil Kumar; Meenakshisunderam, Sivakumaran
Patent: US2010/29940 A1, 2010 ;
Location in patent: Page/Page column 9 ;
反应条件
1: With diisobutylaluminium hydride in toluene
T=-5 - 5°C; 3 h;
2: With water; acetic acid in ethyl acetate; toluene
参考文献
UNICHEM LABORATORIES LIMITED
Patent: WO2006/100689 A1, 2006 ;
Location in patent: Page/Page column 10 ;
反应条件
1: With methyl chloroformate in tetrahydrofuran
T=0 - 5°C; 0.5 h;
2: With sodium tetrahydroborate in tetrahydrofuran
T=0 - 20°C; 30 h;
3: With hydrogenchloride in tetrahydrofuran; water
Product distribution / selectivity;
参考文献
AUROBINDO PHARMA LIMITED
Patent: WO2008/72078 A1, 2008 ;
Location in patent: Page/Page column 17 ;
反应条件
1: potassium carbonate / acetone / 4.17 h / 20 °C
2: sodium hydride / tetrahydrofuran; mineral oil / 48 h / 25 °C
3: triethylamine / dichloromethane / 17 h / -5 °C / Inert atmosphere
4: Oxonereg;; sodium hydrogencarbonate / tetrabutyl-ammonium chloride / dichloromethane; water; acetone / 16 h / 0 - 20 °C
5: 1,4-diaza-bicyclo[2.2.2]octane / 1,4-dioxane / 24 h / 40 °C
View Scheme
参考文献
LEK PHARMACEUTICALS D.D.; CASAR, Zdenko; STERK, Damjan; JUKIC, Marko
Patent: WO2012/13325 A1, 2012 ;
反应条件
1: sodium hydride / tetrahydrofuran; mineral oil / 48 h / 25 °C
2: triethylamine / dichloromethane / 17 h / -5 °C / Inert atmosphere
3: Oxonereg;; sodium hydrogencarbonate / tetrabutyl-ammonium chloride / dichloromethane; water; acetone / 16 h / 0 - 20 °C
4: 1,4-diaza-bicyclo[2.2.2]octane / 1,4-dioxane / 24 h / 40 °C
View Scheme
参考文献
LEK PHARMACEUTICALS D.D.; CASAR, Zdenko; STERK, Damjan; JUKIC, Marko
Patent: WO2012/13325 A1, 2012 ;
反应条件
1: triethylamine / dichloromethane / 17 h / -5 °C / Inert atmosphere
2: Oxonereg;; sodium hydrogencarbonate / tetrabutyl-ammonium chloride / dichloromethane; water; acetone / 16 h / 0 - 20 °C
3: 1,4-diaza-bicyclo[2.2.2]octane / 1,4-dioxane / 24 h / 40 °C
View Scheme
参考文献
LEK PHARMACEUTICALS D.D.; CASAR, Zdenko; STERK, Damjan; JUKIC, Marko
Patent: WO2012/13325 A1, 2012 ;
