公开(公告)号：US06562974B2

公开(公告)日：2003-05-13

申请号：US09771899

申请日：2001-01-29

申请人： Frederick Dana Cazer ,  William Douglas Cramer ,  Dennis Michael Billings ,  Gregory Eugene Parry

发明人： Frederick Dana Cazer ,  William Douglas Cramer ,  Dennis Michael Billings ,  Gregory Eugene Parry

IPC分类号： C07F958

CPC分类号： C07F9/3873 ,  C07F9/386 ,  C07F9/58

摘要： The present invention relates to a novel process for making geminal bisphosphonates. The process provides for bisphosphorylation using phosphorus trihalide, phosphorous acid as a reactant/solvent, and a base as an acid acceptor/solvent. The present invention is directed to a process for making geminal bisphosphonates of the general formula: wherein Q is oxygen, —NR4—, sulfur, selenium, or a single bond; m+n is an integer from 0 to about 5, Z is a ring selected from the group consisting of pyridine, pyridazine, pyrimidine, and pyrazine; R1 is hydrogen, substituted or unsubstituted amino, amido, hydroxy, alkoxy, halogen, carboxylate, substituted or unsubstituted alkyl (saturated or unsaturated) having from 1 to about 6 carbon atoms, substituted or unsubstituted aryl, or substituted or unsubstituted benzyl; each R2 is independently, hydrogen, or substituted or unsubstituted alkyl (saturated or unsaturated) having from 1 to about 4 carbon atoms; R3 is one or more substituents selected from the group consisting of hydrogen, substituted or unsubstituted alkyl (saturated or unsaturated) having from 1 to about 6 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted benzyl, hydroxy, halogen, carbonyl, alkoxy, nitro, amido, amino, substituted amino, carboxylate, and combinations thereof; R4 is hydrogen, substituted alkyl (saturated or unsaturated) having from 1 to about 4 carbon atoms, or acyl.

摘要翻译： 本发明涉及一种制备偕双膦酸盐的新方法。 该方法提供使用三卤化磷，亚磷酸作为反应物/溶剂和碱作为酸受体/溶剂的双磷酸化。 本发明涉及制备以下通式的偕二膦酸盐的方法：其中Q为氧，-NR4-，硫，硒或单键; m + n是0至约5的整数，Z是选自吡啶，哒嗪，嘧啶和吡嗪的环; R 1是氢，取代或未取代的氨基，酰氨基，羟基，烷氧基，卤素，羧酸酯，取代或未取代的具有1至约6个碳原子的烷基（饱和或不饱和的），取代或未取代的芳基或取代或未取代的苄基; 每个R 2独立地为氢，或具有1至约4个碳原子的取代或未取代的烷基（饱和或不饱和的）; R3是一个或多个选自氢，取代或未取代的具有1至约6个碳原子的烷基（饱和或不饱和的），取代和未取代的芳基，取代和未取代的苄基，羟基，卤素，羰基，烷氧基， 硝基，酰胺基，氨基，取代的氨基，羧酸酯及其组合; R4是氢，具有1至约4个碳原子的取代烷基（饱和或不饱和的）或酰基。