Patent EP-0136543-A2 (EP)
Title: Method for the preparation of nucleosidealkyl, aralkyl and aryl phosphonites and phosphonates
Inventor: ENGELS JOACHIM DR
IPC: C07H21/00
Filed: 1984-08-30
Abstract: 1. Claims for the contracting states : BE, CH, LI, DE, FR, GB, IT, LU, NL, SE A process for the preparation of deoxyribonucleoside phosphonates of the general formula I  see diagramm : EP0136543,P14,F1  in which T denotes a protecting group for a primary hydroxyl group, B denotes a nucleoside base radical in which any exoamino group present is protected, G denotes a protecting group for a secondary hydroxyl group, Z denotes oxygen, sulfur or selenium and R denotes alkyl having up to 8 C atoms, cyclohexyl, benzyl, or phenyl which is optionally substituted by fluorine, chlorine, bromine, lower alkyl, lower alkoxy or trifluoromethyl, characterized in that a difunctional phosphonylating reagent of the general formula II  see diagramm : EP0136543,P14,F2  in which X denotes chlorine or Y and Y denotes a group of the formula  see diagramm : EP0136543,P14,F3  R**1 and R**2 representing identical or different alkyl or cycloalkyl radicals having up to 8 C atoms, or phenyl radicals, or R**1 and R**2 , together with the nitrogen, representing a saturated or unsaturated heterocyclic ring which can contain further hetero atoms, being reacted with a nucleoside of the general formula III  see diagramm : EP0136543,P14,F4  in which T and B have the meanings given above, the resulting compound of the general formula IV  see diagramm : EP0136543,P14,F5  being reacted with a compound of the general formula V  see diagramm : EP0136543,P15,F1  in which B and G have the meanings given above, and the resulting compounds of the general formula VI  see diagramm : EP0136543,P15,F2  in which T, R, B and G have the meanings given above, being oxidatively converted to compound of the general formula I. 1. Claims for the contracting state AT A process for the preparation of deoxyribonucleoside phosphonates of the general formula I  see diagramm : EP0136543,P15,F3  in which T denotes a protecting group for a primary hydroxyl group, B denotes a nucleoside base radical in which any exoamino group present is protected, G denotes a protecting group for a secondary hydroxyl group, Z denotes oxygen, sulfur or selenium and R denotes alkyl having up to 8 C atoms, cyclohexyl, benzyl, or phenyl which is optionally substituted by fluorine, chlorine, bromine, lower alkyl, lower alkoxy or trifluoromethyl, characterized in that a difunctional phosphonylating reagent of the general formula II  see diagramm : EP0136543,P16,F1  in which X denotes chlorine or Y and Y denotes a group of the formula  see diagramm : EP0136543,P16,F2  R**1 and R**2 representing identical or different alkyl or cycloalkyl radicals having up to 8 C atoms, or phenyl radicals, or R**1 and R**2 , together with the nitrogen, representing a saturated or unsaturated heterocyclic ring which can contain further hetero atoms, being reacted with a nucleoside of the general formula III  see diagramm : EP0136543,P16,F3  in which T and B have the meanings given above, the resulting compound of the general formula IV  see diagramm : EP0136543,P16,F4  being reacted with a compound of the general formula V  see diagramm : EP0136543,P16,F5  in which B and G have the meanings given above, and the resulting compounds of the general formula VI  see diagramm : EP0136543,P17,F1  in which T, R, B and G have the meanings given above, being oxidatively converted to compound of the general formula I.