Chlorotrimethylsilane → Adenine

HRID 1385538Notes

Reaction equation

HRID 1385538 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-β-D-ribofuranosyl)adenine was prepared from 9-β-D-arabinofuranosyladenine in a five-step synthesis using a modification of a procedure reported by M. Ikehara at al., Nucleosides and Nucleotides Vol. 2, pp. 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. Vol. 104, pg. 1316 (1982). Selective protection of the 3′ and 5′-hydroxyl groups of N6-Benzoyl-9-β-D-arabinofuranosyladenine with tetrahydropyranyl (THP) was accomplished by modification of a literature procedure G. Butke, et al., in Nucleic Acid Chemistry, Part 3, pp. 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-tetrahydropyran-2-yl)-β-D- arabinofuranosyl]adenine with trifluoromethanesulfonic anhydride in dichloromethane gave the 2′-triflate derivative N6-Benzoyl-9-[2′-O-trifluoro-methylsulfonyl-3′,5′-di-O-tetrahydropyran-2-yl)-β-D-arabinofuranosyl]adenine which was not isolated due to its lability. Displacement of the 2′-triflate group was effected by reaction with tetrabutyl ammonium fluoride in tetrahydrofuran to obtain a moderate yield of the 2′-fluoro derivative N6-Benzoyl-9-[2′-fluoro-3′,5′-di-O-tetra-hydropyran-2-yl)-β-D-arabinofuranosyl]adenine. Deprotection of the THP groups of N6-Benzoyl-9-[2′-fluoro-3′,5′-di-O-tetrahydro-pyran-2-yl)-β-D-arabinofuranosyl]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 was in agreement with the literature values. M. Ikehara and H. Miki, Chem. Pharm. Bull., Vol. 26, pp. 2449-2453 (1978). Standard methodologies such as those of foregoing examples 3 and 4 were employed to obtain the 5′-dimethoxytrityl-3′-phos-phoramidite intermediates N6-Benzoyl-9-[2′-fluoro-5′-O-(4,4′-di-methoxytrityl)-β-D-ribofuranosyl]adenine and N6-Benzoyl-[2′-deoxy-2′-fluoro-5′-O-(4,4′-dimethoxytrityl)]adenosine-3′-O-(N,N-diisopropyl-β-cyanoethyl phosphoramidite). K. K. Ogilvie, Can J. Chem. Vol. 67, pp. 831-839 (1989).

Workup

  1. customin good yield

Sources & evidence

ORD record
ord-fb764e8395864161995c6412b67b8490
Source dataset
uspto-grants-2001_07
Patent number
US06262241B1

Reaction notes

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