N-[4-(4-氟苯基)-6-(1-甲基乙基)-5-[(1E)-3-氧代-1-丙烯基]-2-嘧啶基]-N-甲基-甲烷磺酰胺合成路线 （共 11 条）
反应条件
dipyridinium dichromate in dichloromethane
T=20°C; 5.25 h; Molecular sieve;
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
1: With diisobutylaluminium hydride in toluene
T=-9 - 25°C;
2: With methanol in toluene
参考文献
ASTRAZENECA UK LIMITED
Patent: WO2007/7119 A1, 2007 ;
Location in patent: Page/Page column 6; 25-26 ;
WO 2007/007119 A1
反应条件
1: With trichlorophosphate
T=0 - 85°C; 36 h;
2: With sodium hydroxide in water
pH=8 - 8.5; 1 h; Cooling with ice; Product distribution / selectivity;
参考文献
AUROBINDO PHARMA LIMITED; MALLELA, Sambhu Prasad Sarma; NANDI, Sukumar; NANGI, Gangadhara Bhima Shankar; ANANTA, Rani; MEENAKSHISUNDERAM, Sivakumaran
Patent: WO2010/38124 A1, 2010 ;
Location in patent: Page/Page column 19-20 ;
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
6: acetic anhydride; dimethyl sulfoxide / 24 h / 20 °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
5: acetic anhydride; dimethyl sulfoxide / 24 h / 20 °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
4: acetic anhydride; dimethyl sulfoxide / 24 h / 20 °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: Oxonereg;; sodium hydrogencarbonate / tetrabutyl-ammonium chloride / dichloromethane; water; acetone / 16 h / 0 - 20 °C
2: 1,4-diaza-bicyclo[2.2.2]octane / 1,4-dioxane / 24 h / 40 °C
3: acetic anhydride; dimethyl sulfoxide / 24 h / 20 °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 hydrogencarbonate; water / 1 h / 100 °C
2: acetic anhydride; dimethyl sulfoxide / 24 h / 20 °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: 1,4-diaza-bicyclo[2.2.2]octane / 1,4-dioxane / 24 h / 40 °C
2: acetic anhydride; dimethyl sulfoxide / 24 h / 20 °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: trans-N-(4-(4-fluorophenyl)-6-isopropyl-5-(3-oxoprop-1-enyl)pyrimidin-2-yl)-N-methylmethanesulfonamide With lithium chloride; (S)-(-)-1,1'-bi-(2-naphthyloxy)(diisopropoxy)titanium in tetrahydrofuran
T=20°C; 0.166667 h;
2: 1-ethoxy-1,3-bis-(trimethylsilanyloxy)-buta-1,3-diene With N,N,N',N,-tetramethylethylenediamine in tetrahydrofuran
T=20°C;
3: With phosphoric acid; trifluoroacetic acid
more than 3 stages;
参考文献
ASTRAZENECA UK LIMITED
Patent: WO2007/7119 A1, 2007 ;
Location in patent: Page/Page column 20 ;
WO 2007/007119 A1
