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    • 7. 发明申请
    • PROCESS FOR THE PREPARATION OF 4-CHLOROPYRIDINE-N-OXIDES
    • 制备4-氯吡啶-N-氧化物的方法
    • WO2002102779A1
    • 2002-12-27
    • PCT/NL2002/000379
    • 2002-06-11
    • DSM N.V.BODE DE, RonusLIEBREGTS, Constantinus, Simon, MariaZWAAN, Wilhelmus
    • BODE DE, RonusLIEBREGTS, Constantinus, Simon, MariaZWAAN, Wilhelmus
    • C07D213/89
    • C07D213/89
    • Process for the preparation of a 4-chloropyridine-N-oxide of formula (1) in which R 1 , R 2 and R 3 each independently stand for H, an alkyl group or an alkoxy group and R 4 stands for an alkyl group or an alkoxy group, in which the corresponding 4-H-pyridine-N-oxide is subjected to a treatment with Cl 2 , resulting in the formation of 4-Cl-pyridine-N-oxide. Preferably R 1 stands for H, R 2 stands for H or methyl, and R 3 and R 4 both stand for CH 3 , or R 1 and R 2 both for H, R 3 for methoxy and R 4 for methyl. Preferably the chlorination is carried out in the presence of a base, for example an (earth) alkali metal hydroxide or carbonate, and water, and use is made of between 1 and 3 base equivalents, calculated relative to the quantity of 4-H-pyridine-N-oxide and 0 to 10 equivalents of water, calculated relative to the quantity of 4-H-pyridine-N-oxide. The 4-Cl-pyridine-N-oxide obtained can subsequently be subjected to a treatment with a substituted or unsubstituted alcohol in the presence of a base. The resulting compounds are suitable for use in the preparation of pharmaceuticals, for example omeprazol, pantoprazol, rabeprazol and lansoprasol.
    • 制备式(1)的4​​-氯吡啶-N-氧化物的方法,其中R 1,R 2和R 3各自独立地代表H,烷基或烷氧基, 4>代表烷基或烷氧基,其中相应的4-H-吡啶-N-氧化物用Cl 2处理,导致形成4-Cl-吡啶-N-氧化物。 R 1代表H,R 2代表H或甲基,R 3和R 4均代表CH 3,或R 1和R 2均为H,R' 3>甲氧基,R 4为甲基。 优选地,氯化在碱例如(碱土金属氢氧化物或碳酸盐)和水的存在下进行,并且使用1至3个碱当量,相对于4-H- 吡啶-N-氧化物和0至10当量的水,相对于4-H-吡啶-N-氧化物的量计算。 得到的4-Cl-吡啶-N-氧化物随后可以在碱的存在下用取代或未取代的醇进行处理。 所得化合物适用于制备药物,例如奥美拉唑,泮托拉唑,雷贝唑和兰索普索。