Chlorotrimethylsilane → Adenine

HRID 1418286Notes

Reaction equation

HRID 1418286 reaction equation
Cl[Si](C)(C)C.C([NH:14][C:15]1[N:23]=[CH:22][N:21]=[C:20]2[C:16]=1[N:17]=[CH:18][N:19]2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O)(=O)C1C=CC=CC=1>>[N:23]1[C:15]([NH2:14])=[C:16]2[C:20]([N:19]=[CH:18][NH:17]2)=[N:21][CH:22]=1

Participants

3

Reactant 2

HCID 6397ChlorotrimethylsilaneHCID 12919588HCID 12919588, compound

Product 1

HCID 190Adenine

Procedure

N6 -Benzoyl-9-(2'-fluoro-b-D-ribofuranosyl)adenine was prepared from 9-b-D-arabinofuranosyladenine in a five-step synthesis using a modification of a procedure reported by M. Ikehara at al., Nucleosides and Nucleotides 2:373-385 (1983). Thus, the N6 -benzoyl derivative was obtained in good yield utilizing the method of transient protection with chlorotrimethylsilane. R. A. Jones, J. Am. Chem. Soc. 104:1316 (1982). Selective protection of the 3' and 5'-hydroxyl groups of N6 -Benzoyl-9-β-D-arabinofuranosyladenine with tetrahydro-pyranyl (THP) was accomplished by modification of a literature procedure G. Butke, et al., in Nucleic Acid Chemistry, Part 3:149-152, Townsend, L. B. and Tipson, R. S. eds., (J. Wiley and Sons, New York 1986) to yield N6 -Benzoyl-9-[3',5'-di-O-tetrahydropyran-2-yl)-β-D-arabino furanosyl]adenine in good yield. Treatment of N6 -Benzoyl-9-[3',5'-di-O-tetrahydro-pyran-2-yl)-β-D-arabinofuranosyl]adenine with trifluoromethanesulfonic anhydride in dichloromethane gave the 2'-tri-flate derivative N6 -Benzoyl-9-[2'-O-trifluoromethylsulfonyl-3',5'-di-O-tetrahydropyran-2-yl)-β-D-arabino furanosyl]adenine which was not isolated due to its lability. Displacement of the 2'-triflate group was effected by reaction with tetra-butylammonium fluoride in tetrahydrofuran to obtain a moderate yield of the 2'-fluoro derivative N6 -Benzoyl-9-[2'-fluoro-3',5'-di-O-tetrahydropyran-2-yl)-β-D-arabino furanosyl]-adenine. Deprotection of the THP groups of N6 -Benzoyl-9-[2'-fluoro-3',5'-di-O-tetrahydropyran-2-yl)-β-D-arabino-furanosyl]adenine was accomplished by treatment with Dowex-50W in methanol to yield N6 -benzoyl-9-(2'-deoxy-2'-fluoro-β-D-ribofuranosyl)adenine in moderate yield. The 1H-NMR spectrum of 6 was in agreement with the literature values. M. Ikehara and H. Miki, Chem. Pharm. Bull. 26:2449-2453 (1978). Standard methodologies were employed to obtain the 5'-dimeth-oxytrityl-3'-phosphoramidite intermediates N6 -Benzoyl-9-[2'-fluoro-5'-O-(4,4'-dimethoxytrityl)-β-D-ribofuranosyl]adenine and N6 -Benzoyl-[2'-deoxy-2'-fluoro -5'-O-(4,4'-dimethoxytrityl)]adenosine-3'-O-(N,N-diisopropyl-β-cyanoethylphosphoramidite. K. K. Ogilvie, Can J. Chem. 67:831-839 (1989).

Workup

  1. customin good yield

Sources & evidence

ORD record
ord-184f6c686aad480ba53cbac28fb4eddb
Source dataset
uspto-grants-1999_03
Patent number
US05882927

Reaction notes

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