Chlorotrimethylsilane → Adenine

HRID 1861029Notes

Reaction equation

HRID 1861029 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-β-D-arabinofuranosyladenine in a five-step synthesis using a modification of a procedure reported by Ikehara at al. [Nucleosides and Nucleotides, 2, 373-385 (1983)]. The N-benzoyl derivative was obtained in good yield utilizing the method of transient protection with chlorotrimethylsilane. 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 tetrahydropyranyl (THP) was accomplished by modification of the literature procedure according to Butke et al. [Nucleic Acid Chemistry, Part 3, p.149, L. B. Townsend and R. S. Tipson, Eds., J. Wiley and Sons, New York, 1986], to yield N6-Benzoyl-9-[3′, 5′-di-O-tetrahydropyran-2-yl)-β-D-arabinofuranosyl]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-trifluoromethylsulfonyl-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 tetrabutylammonium 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-arabinofuranosyl]adenine. Deprotection of the THP groups of N6 -Benzoyl-9-[2′-fluoro-3′,5′-di-β-tetrahydropyran-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. [Ikehara and Miki, Chem. Pharm. Bull., 26, 2449 (1978)]. Standard methodologies were employed to obtain the 5′-dimethoxytrityl-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. [Ogilvie, Can J. Chem., 67, 831-839 (1989)].

Workup

  1. customin good yield

Sources & evidence

ORD record
ord-470dbdb43e454787849e3cf2b64aca6e
Source dataset
uspto-grants-2003_03
Patent number
US06531584B1

Reaction notes

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