ChemicalBook CAS DataBase List Acyclovir

Acyclovir synthesis

6synthesis methods

Product Name:Acyclovir
CAS Number:59277-89-3
Molecular formula:C8H11N5O3
Molecular Weight:225.2

Acyclovir, 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one (36.1.5), is synthesized by alkylating guanine with 1-benzoyloxy-2-chloromethoxyethane in triethylamine. The hydroxyl and amino groups of guanine are previously protected with a trimethylsilyl group by being treated with hexamethyldisilazane. After hydrolysis the resulting product with water, 9-(2-benzoyloxymethoxymethyl)guanine (36.1.4) is isolated. Treating this with a methanol solution of ammonia removes the benzoyl protecting group from the hydroxyethoxymethyl fragment, giving acyclovir.

Another way of preparing acyclovir begins with 2,6-dichloropurine, which is alkylated with the same 1-benzoyloxy-2-chloromethoxyethane, but in a triethylamine—dimethylformamide system to make 2,6-dichloro-9-(2-benzoyloxyethoxymethyl)purine (36.1.6). Treating this with a methanol solution of ammonia replaces both chlorine atoms with amino groups, and subsequent diazotization using sodium nitrite in dilute acetic acid selectively replaces one of the two amino groups for a hydroxyl group, in particular the amino group at position C6 of the purine system. Finally, treating the product with a methanol solution of ammonia removes the benzoyl protection from the synthesized 9-(2-benzoyloxyethoxymethyl)guanine (36.1.4) to make acyclovir.

75128-73-3 Synthesis

9-[(2-Acetoxyethoxy)methyl]-N2-acetylguanine

75128-73-3
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$6.00/1g

59277-89-3
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$5.00/250mg

Yield:59277-89-3 92%

Reaction Conditions:

with sodium hydroxide

Steps:

EXAMPLES:

Example 4 Synthesis of acyclovir from 9-((2-acetoxyethoxy) methyl)-N² -acetylguanine. To 5.0 g of 9-((2-acetoxyethoxy)methyl)-N² -acetylguanine was added 50 ml of an aqueous 5% sodium hydroxide solution, and the mixture was sitrred for 24 hours at room temperature for reaction. The resulting reaction solution was neutralized with 1N hydrochloric acid, and the precipitated crystals were collected by filtration, whereby 3.2 g of acyclovir was obtained. Yield, 92%. ¹ H NMR (300 MHz, DMSO-d₆) analytical values: δ, 3.47 (4H, brs, H-3' & 4'), 4.66 (1H, brs, OH), 5.35 (2H, s, H-1'), 6.49 (2H, brs, NH₂), 7.81 (1H, s. H-8). Mass spectral analytical value: MH⁺ =226.

References:

US5336770,1994,A

646-06-0 Synthesis