# US 2017/0253584 A1 · Preparation of 2'-fluoro-2'-alkyl-substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2017/0253584 A1
- Document ID: US20170253584A1
- Status: Published application
- Kind: A1
- Application number: 15/425,198
- Filed: 2017-02-06
- Published: 2017-09-07
- Earliest claimed: 2004-09-14
- Assignees: Gilead Pharmasset LLC
- Inventors: Byoung Kwon Chun; Jinfa Du; Suguna Rachakonda; Peiyuan Wang
- Web page: https://patentgrep.com/patent/US20170253584A1

## CPC

- C07D 411/04: directly linked by a ring-member-to-ring-member bond
- A61K 31/7072: having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
- A61P 31/14: for RNA viruses
- C07D 307/20: Oxygen atoms
- C07D 307/33: in position 2, the oxygen atom being in its keto or unsubstituted enol form
- C07D 317/00: Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D 317/30: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- C07D 407/04: directly linked by a ring-member-to-ring-member bond
- C07H 15/203: Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
- C07H 19/06: Pyrimidine radicals
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)

## Abstract

The present invention provides (i) processes for preparing a 2′-deoxy-2′-fluoro-2′-methyl-D-ribonolactone derivatives, (ii) conversion of intermediate lactones to nucleosides with potent anti-HCV activity, and their analogues, and (iii) methods to prepare the anti-HCV nucleosides containing the 2′-deoxy-2′-fluoro-2′-C-methyl-β-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside.

## Claims

### Claim 1

A compound of formula
wherein
R′ and R″ are independently H, lower alkyl (C1-C6), aryl (C6-C20), optionally substituted benzyl, trialkylsilyl, t-butyl-dialkylsilyl, t-butyldiphenylsilyl, TIPDS, THP, MOM, MEM, acetyl, benzoyl, or optionally substituted acyl; or R′ and R″ form a cyclopentyl or cyclohexanyl group;
R1 and R2 are independently H, lower alkyl (C1-C6), aryl (C6-C20), hydroxymethyl, methoxymethyl, halomethyl, optionally substituted ethenyl, halovinyl, optionally substituted ethynyl, or optionally substituted allyl; and
R3 is H, aryl, arylalkyl, or lower alkyl (C1-C6).

### Claim 2 (depends on 1)

The compound of claim 1,
wherein
R′ and R″ are independently H or lower alkyl (C1-C6);
R1 and R2 are independently H, or lower alkyl (C1-C6); and
R3 is H or lower alkyl (C1-C6).

### Claim 3

A compound of formula
wherein
each R1 is independently lower alkyl (C1-C6), optionally substituted phenyl, or optionally substituted benzyl; or R1 forms a cyclopentyl or cyclohexanyl group;
R2 and R3 are independently hydrogen, lower alkyl (C1-C6), hydroxymethyl, methoxymethyl, halomethyl, optionally substituted ethenyl, halovinyl, optionally substituted ethynyl, or optionally substituted allyl; and
R4 is independently arylalkyl, or lower alkyl (C1-C10).

### Claim 4 (depends on 3)

The compound of claim 3,
wherein
each R1 is independently lower alkyl (C1-C6);
R2 and R3 are independently hydrogen, or lower alkyl (C1-C6); and
R4 is independently lower alkyl (C1-C10).

### Claim 5 (depends on 3)

The compound of claim 3, having the formula

### Claim 6

A compound of formula
wherein
R2 and R3 are independently H, alkyl (C1-C10), hydroxymethyl, methoxymethyl, halomethyl, optionally substituted ethenyl, halovinyl, optionally substituted ethynyl, or optionally substituted allyl;
R5 and R6 are methoxymethyl, methoxyethyl, benzyloxymethyl, ethoxymethyl, trityl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, acetyl, pivaloyl, benzoyl, toluoyl, 4-phenyl benzoyl, 2-nitrobenzoyl, 3-nitrobenzoyl, 4-nitrobenzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, or substituted benzoyl;
Nu is F, Cl, Br, N3, CN, NO3, SCN, OR or NR2 wherein R is acyl or lower alkyl (C1-C10); and
L is a leaving group.

### Claim 7 (depends on 6)

The compound of claim 6,
wherein
R2 and R3 are independently H, alkyl (C1-C10), or halomethyl;
R5 and R6 are benzoyl;
Nu is F; and
L is OAc.

### Claim 8 (depends on 7)

The compound of claim 7, wherein R2 is H and R3 is methyl.

### Claim 9

A compound of formula

### Claim 10

A compound of formula IIIa, IIIb or IIIc
wherein
each R1 is independently lower alkyl (C1-C6), optionally substituted phenyl, or optionally substituted benzyl;
R2 and R3 are independently hydrogen, lower alkyl (C1-C6), hydroxymethyl, methoxymethyl, halomethyl, optionally substituted ethenyl, optionally substituted ethynyl, or optionally substituted allyl; and
R4 is independently hydrogen, aryl, arylalkyl, or lower alkyl (C1-C10).

### Claim 11 (depends on 10)

The compound of claim 10,
wherein
each R1 is lower alkyl (C1-C6);
R2 and R3 are independently hydrogen, or lower alkyl (C1-C6); and
R4 is lower alkyl (C1-C10).

### Claim 12 (depends on 10)

The compound of claim 10, having the formula