Acetic acid (2R,3R,4R,5R)-3,4-diacetoxy-5-(6-chloro-2-iodo-purin-9-YL)-tetrahydro-furan-2-ylmethyl ester → (2R,3R,4R,5R)-4-(Acetyloxy)-2-[(acetyloxy)methyl]-5-(6-chloro-2-cyano-9H-purin-9-yl)tetrahydro-3-furanyl acetate

HRID 1700097Notes

Reaction equation

[C:1]([O:4][C@H:5]1[C@@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@H:8]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][C:17](I)=[N:18][C:19]=3[Cl:23])[O:7][C@@H:6]1[CH2:25][O:26][C:27](=[O:29])[CH3:28])(=[O:3])[CH3:2].[Cu](C#N)[C:31]#[N:32]>CN(C)C=O>[C:1]([O:4][C@H:5]1[C@@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@H:8]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][C:17]([C:31]#[N:32])=[N:18][C:19]=3[Cl:23])[O:7][C@@H:6]1[CH2:25][O:26][C:27](=[O:29])[CH3:28])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 115 °C

Procedure

A mixture of (2R,3R,4R,5R)-4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(6-chloro-2-iodo-9H-purin-9-yl)tetrahydro-3-furanyl acetate (J. Med. Chem., 1992, 35, 248) (0.5 g, 0.93 mmol) and copper (II) cyanide (0.11 g, 1.23 mmol) in N,N-dimethylformamide was heated at 115° C. for 90 minutes. The solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel eluting with dichloromethane:ethyl acetate (4:1 by volume) to give a product which was then azeotroped sequentially with dichloromethane and diethyl ether to afford the title compound as a solid (0.22 g).

Workup

customThe solvent was removed under reduced pressure
customthe residue was purified by column chromatography on silica gel eluting with dichloromethane:ethyl acetate (4:1 by volume)
customto give a product which
customwas then azeotroped sequentially with dichloromethane and diethyl ether

Sources & evidence

ORD record: ord-a8d3398ddd294b5db1c113fd8c0bb097
Source dataset: uspto-grants-2002_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06350735B1

Reaction notes

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