55343-28-7

Upstream product

• 98-88-4 benzoyl chloride 
• 707-99-3 9-(2-hydroxyethyl)adenine 

Downstream Products

• 135711-65-8 3'-Deoxy-5'-O-(monomethoxytrityl)-N⁶-<2-(4-nitrophenyl)ethoxycarbonyl>adenylyl-(2'-(O^P-<2-(4-nitrophenyl)ethyl>)->5')-3'-deoxy-N⁶-<2-(4-nitrophenyl)ethoxycarbonyl>adenylyl-(2'-(O^P-<2-nitrophenyl)ethyl)->2')-N⁶-benzoyl-9-(2'-hydroxyethyl)..... 
• 106941-25-7 Adefovir 
• 123156-01-4 9-(2-diethoxyphosphonylethyl)-N⁶-benzoyladenine 

Relevant academic research and scientific papers

Intramolecular cyclization of some acyclic nucleoside analogs

Reaction of stereoisomeric 8-bromo-9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenines (8) with concentrated aqueous ammonia, sodium hydride, potassium tert-butoxide, or 1,8-diazabicyclo-[5,4,0]undec-7-ene afforded 4′-O,8-anhydro-9-(2,3-O-isopropyliden

PHOSPHONYLMETHOXYALKYL AND PHOSPHONYLALKYL DERIVATIVES OF ADENINE

Analogues of the antivirals (2S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (Ia) and 9-(2-phosphonylmethoxyethyl)adenine (Ib), modified in the alkyl chain, are described.The phosphonylmethoxyalkyl derivatives were prepared by condensation of sodium alkoxides of hydroxyalkyladenines (or their N-protected derivatives) with dimethyl p-toluenesulfonyloxymethanephosphonate (II) followed by alkaline hydrolysis and reactions with halotrimethylsilane, or by reaction of vicinal dihydroxyalkyl derivatives with chloromethanephosphonyl dichloride (XIV) and subsequent cyclization of the intermediates XV in aqueous alkali.In the second case the pure regioisomers were also obtained from substituted dihydroxy derivatives with one free hydroxyl group.The following compounds were prepared in this way: 3-O-methyl ether IIIc and 3-O-octyl ether IVc, 9-(3-phosphonylmethoxypropyl)- (Vc), 9-(4-phosphonylmethoxybutyl)- (Vf), 9-(5-phosphonylmethoxypentyl) (Vi), 9-(2-phosphonylmethoxypropyl)- (VIc), 9-(1-phosphonylmethoxy-3-hydroxy-2-propyl)- (XIIc), 9-(2-methoxy-3-phosphonylmethoxypropyl)- (XIIIc), erythro-9-(2-phosphonylmethoxy-3,4-dihydroxybutyl)- (VIIc), and threo-9-(4-phosphonylmethoxy-2,3-dihydroxybutyl)adenine (IXc) and its enantiomer (Xc). 9-(2-Phosphonylmethoxy-3,3-dihydroxypropyl)adenine (VIII) was obtained by oxidation of VIIc with sodium periodate, 9-(2-phosphonylmethoxyethoxymethyl)adenine (XIc) by reaction of II with sodium salt of 9-(2-hydroxyethoxymethyl)adenine (XIa). 9-(1,2-Dihydroxy-2-methyl-3-propyl)adenine 1- and 2-phosphonylmethyl ether (XVIb), 9-(3,4-dihydroxybutyl)adenine 3- and 4-phosphonylmethyl ether (XVIIb) and 9-(2,3-dihydroxybutyl)adenine 2- and 3-phosphonylmethyl ether (XVIIIb) were prepared by reaction chloromethanephosphonyl dichloride (XIV) followed by alkaline treatment.Analogous reaction was also employed in the preparation of regioisomerically pure 1-phosphonylmethyl ethers of 9-(1,2-dihydroxy-3-butyl)adenine (XXIV), 9-(1,2-dihydroxy-2-methyl-3-propyl)adenine (XVIb) and 9-(1,2-dihydroxy-3-nonyl)adenine (XXV).Alkylation of adenine with diethyl chloromethoxymethanephosphonate (XXVII) followed by hydrolysis afforded 9-(phosphonylmethoxymethyl)adenine (XXVIIIb). 9-(Phosphonylmethyl)adenine (XLI) was obtained by condensation of adenine with compound II.Conversion of 9-(ω-hydroxyalkyl)adenines into the ω-halogenoalkyl derivatives followed by reaction with trialkyl phosphite and cleavage was used in the preparation of 9-(2-phosphonylethyl)adenine (XXXIVa), 9-(4-phosphonylbutyl)adenine (XXXIVb) and 9-(2-phosphonylethoxymethyl)adenine (XXXIX). 9-(2-Phosphonyl-2-hydroxyethyl)adenine (Lc) and 9-(3-phosphonyl-3-hydroxypropyl)adenine (Lb) were synthesized by treatment of ω-(adenin-9-yl)alkanals with dialkyl phosphite and subsequent cleavage with halogenotrimethylsilane; the same procedure converted 9-(2-oxopropyl)adenine (XLVIIIa) into 9-(2-phosphonyl-2-hydroxypropyl)adenine (La).

SYNTHESIS OF 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE AND RELATED COMPOUNDS

Diethyl 2-hydroxyethoxymethanephosphonate (VIII) was converted into diethyl 2-halogenoethoxymethanephosphonates IXa and IXb by reaction with triphenylphosphine and tetrachloromethane or tetrabromomethane; analogous reaction of VIII with p-toluenesulfonyl chloride afforded diethyl 2-(p-toluenesulfonyloxy)ethoxymethanephosphonate (IXc).Reaction of sodium salt of adenine with compounds IX led to 9-(2-diethoxyphosphonylmethoxyethyl)adenine (X).Compound X was converted into 9-(2-phosphonylmethoxyethyl)adenine (II) by treatment with bromotrimethylsilane whereas alkaline hydrolysis of X gave ethyl ester Vb.Reaction of 9-(2-hydroxyethyl)adenine (IIIa) or its N6-benzoyl derivative IIIb with dimethyl p-toluenesulfonyloxymethanephosphonate (IV) in the presence of sodium hydride, followed by alkaline hydrolysis yielded methyl ester Va.Morpholide XI reacted with an inorganic phosphate and diphosphate to give 9-(2-phosphorylphosphonylmethoxyethyl)adenine (XII) and 2-(diphosphorylphosphonylmethoxyethyl)adenine (XIII), respectively.