Process for acyclic phosphonate nucleotide analogs

Organic compounds -- part of the class 532-570 series – Organic compounds – Four or more ring nitrogens in the bicyclo ring system

Reexamination Certificate

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Reexamination Certificate

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07737273

ABSTRACT:
The present invention provides a novel process for the preparation of acyclic phosphonate nucleotide analogs using novel intermediates. Thus, for example, (R)-9-(2-phosphonomethoxypropyl)adenine is reacted with dimethylformamide dimethylacetal to give N4-dimethylaminomethyledino-9-(2-phosphonomethoxy ethyl) adenine, which is then reacted with chloromethyl-2-propyl carbonate in presence of triethylamine to give (R)-N4-Dimethylaminomethyledino-9-(2-phosphono methoxypropyl) adenine disoproxil, followed by deprotection with acetic acid to get tenofovir disoproxil. Tenofovir disoproxil is then treated with fumaric acid to give tenofovir disoproxil fumarate.

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patent: 5977061 (1999-11-01), Holy et al.
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patent: WO 03/095665 (2003-11-01), None
patent: WO 2004/037161 (2004-05-01), None
Magdalenajidkova, Milena Masojfdkova and Ivan Rosenberg, Transprotection of N-Benzoylated Nucleobase Derivatives by Dialkylaminomethylene Group, Institute of Organic Chemistry and biochemistry, Academy of Sciences of the Czech Republic, Nucleotides & Nucleotides, 16(12), 2151-2164 (1997), pp. 2151-2164.
PCT Notification of Transmittal of the International Search Reort and the Written Opinion of the International Search Authority, International Application No. PCT/IN2005/000247.

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