Synthesis of 2′-fluoro-6′-methylene-carbocyclic adenosine (FMCA) and 2′-fluoro-6′methylene-carbocyclic guanosine (FMCG)

Patent metadata

Field	Value
Publication number	US-10995093-B2
Application number	US-201916699427-A
Country	US
Kind code	B2
Filing date	Nov 29, 2019
Priority date	Apr 7, 2016
Publication date	May 4, 2021
Grant date	May 4, 2021

Abstract

The invention provides a new convergent approach for the synthesis of 2′-fluoro-6′-methylene-carbocyclic adenosine (FMCA) and 2′-fluoro-6′-methylene-carbocyclic guanosine (FMCG) from a readily available starting material in eight steps. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, (1S,3R, 4R)-3-tert-butoxy-4-(tert-butoxymethyl)-2-fluoro-5-methylenecyclopentanol (compound 8 of scheme 1A or a) in only six (6) steps is also provided. Prodrugs of these compounds are also prepared.

First claim

What is claimed is:

1. A process for preparing the compound 2′-Fluoro-6′-Methylene-Carbocyclic Adenosine (FMCA) compound 10 from compound 8

Comprising condensing an amine protected 6-amino purine compound according to the chemical structure:

where P represents one or two amine protecting groups (preferably two BOC groups) onto compound 8 in the presence of triphenylphosphine and diisopropylazidocarboxylate (DIAD) in solvent to produce compound 8P

where P represents one or two amine protecting groups; and
subjecting compound 8P to deprotection to produce compound 10 (FMCA)

wherein the synthesis is conducted in steps, wherein both compound 8P and 10 are separated and purified.

2. A process for preparing the compound 2′-Fluoro-6′-Methylene-Carbocyclic Adenosine (FMCA) compound 10 from compound 8

Comprising condensing a di-Boc protected 6-amino purine compound according to the chemical structure:

onto compound 8 in the presence of triphenylphosphine and diisopropylazidocarboxylate (DIAD) in solvent to produce compound 9

subjecting compound 9 to deprotection to produce compound 10 (FMCA)

wherein the synthesis is conducted in steps, wherein compounds 9 and 10 are separated and purified.

3. Any one or more of compounds 3, 4, 5, 6, 7, 8, 8P, 9, 9P or 9G hereof or a salt thereof.

Assignees

• Univ Georgia

Inventors

• Chu Chung K
• Mulamootttil Varughese Alexander
• Mishra Ram C
• Singh Uma Sharan

Classifications

• C07D317/44

  ortho- or peri-condensed with carbocyclic rings or ring systems · CPC title

• C07D473/26

  with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both · CPC title

• C07C43/253

  containing hydroxy or O-metal groups · CPC title

• A61P31/20

  for DNA viruses · CPC title

• C07D473/18 Primary

  one oxygen and one nitrogen atom, e.g. guanine · CPC title