128131-83-9

Upstream product

• 136522-33-3 (1S,4R)-4-[2-amino-6-chloro-9H-purin-9-yl]-2-cyclopentene-1-methanol 
• 765-30-0 Cyclopropylamine 
• 171887-04-0 (1R,4S)-1-[(2-amino-6-chloro-5-formamido-4-pyrimidinyl)amino]-4-(hydroxymethyl)-2-cyclopentene 
• 172015-79-1 ((1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)cyclopent-2-en-1-yl)methanol hydrochloride 
• 10310-21-1 2-Amino-6-chloropurin 
• 268737-86-6 cis-3-benzoyloxy-4-(hydroxymethyl)cyclopentene 
• 159418-20-9 (4aR,7aR)-4,4a,5,7a-Tetrahydro-cyclopenta[1,3]dioxin-2-one 
• 151765-22-9 (3S,3aR,6aR)-3-hydroxy-3,3a,4,6a-tetrahydro-2H-cyclopenta[b]furan-2-one 
• 7440-44-0 pyrographite 
• 594-45-6 ethanesulfonic acid 
• 122-51-0 orthoformic acid triethyl ester 
• 1108600-46-9 ((1S,4R)-4-(2-chloro-6-(cyclopropylamino)-9H-purin-9-yl)cyclopent-2-en-1-yl)methanol 

Downstream Products

• 188062-50-2 abacavir sulfate 
• 188062-50-2 {(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol sulphate 
• 261909-26-6 methyl ((((1S,4R)-4-(2-amino-6-(cyclopropyl-amino)-9H-purin-9-yl)cyclopent-2-en-1-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate 

Relevant academic research and scientific papers

Enantioselective syntheses of carbanucleosides from the Pauson-Khand adduct of trimethylsilylacetylene and norbornadiene

(Chemical Equation Presented) A new enantioselective approach to carbanucleosides from Pauson-Khand (PK) adduct 1 is disclosed. The chiral cyclopentenone 1 is readily accessible in enantiomerically pure form via PK reaction of trimethylsilylacetylene and norbornadiene using N-benzyl-N- diphenylphosphino-tert-butyl-sulfinamide as a chiral P,S ligand. (-)-Carbavir and (-)-Abacavir were enantioselectively synthesized starting from (-)-1. The key steps of the sequence are a photochemical conjugate addition of a hydroxymethyl radical, a retro-Diels-Alder reaction, and a palladium catalyzed allylic substitution to introduce the nucleobase.

Enantioselective and Regiodivergent Addition of Purines to Terminal Allenes: Synthesis of Abacavir

The rhodium-catalyzed atom-economic asymmetric N-selective intermolecular addition of purine derivatives to terminal allenes is reported. Branched allylic purines were obtained in high yields, regioselectivity and outstanding enantioselectivity utilizing a Rh/Josiphos catalyst. Conversely, linear selective allylation of purines could be realized in good to excellent regio- and E/Z-selectivity with a Pd/dppf catalyst system. Furthermore, the new methodology was applied to a straightforward asymmetric synthesis of carbocyclic nucleoside abacavir.

Synthesis and Antiviral Evaluation of TriPPPro-AbacavirTP, TriPPPro-CarbovirTP, and Their 1′,2′-cis-Disubstituted Analogues

Herein we describe the synthesis of lipophilic triphosphate prodrugs of abacavir, carbovir, and their 1′,2′-cis-substituted carbocyclic analogues. The 1′,2′-cis-carbocyclic nucleosides were prepared by starting from enantiomerically pure (1R,2S)-2-((benzyloxy)methyl)cyclopent-3-en-1-ol by a microwave-assisted Mitsunobu-type reaction with 2-amino-6-chloropurine. All four nucleoside analogues were prepared from their 2-amino-6-chloropurine precursors. The nucleosides were converted into their corresponding nucleoside triphosphate prodrugs (TriPPPro approach) by application of the H-phosphonate route. The TriPPPro compounds were hydrolyzed in different media, in which the formation of nucleoside triphosphates was proven. While the TriPPPro compounds of abacavir and carbovir showed increased antiviral activity over their parent nucleoside, the TriPPPro compounds of the 1′,2′-cis-substituted analogues as well as their parent nucleosides proved to be inactive against HIV.

Abacavir intermediate and method for purifying same

The invention discloses an abacavir intermediate and a method for purifying the same. The method includes heating mixtures with abacavir intermediate crude products, purified water and water-soluble organic solvents until the abacavir intermediate crude products are completely dissolved so as to obtain mixed liquid; carrying out cooling and crystallization treatment on the mixed liquid; carrying out filtering and drying treatment after crystallization treatment is carried out so as to obtain abacavir intermediate pure products. A structural formula of the abacavir intermediate is shown as a formula IV. The abacavir intermediate and the method have the advantage that the method is easy and convenient to implement and is suitable for industrial production.

PROCESS FOR THE PREPARATION OF AMINO ALCOHOL DERIVATIVES OR SALTS THEREOF

The present invention relates to a process for the preparation of amino alcohol derivatives or salts thereof. In particular the present invention relates to process for the preparation of amino alcohol derivatives or salts thereof which may be used as intermediates in the preparation of HIV reverse transcriptase inhibitors, more preferably Carbovir and Abacavir. The present invention more specifically relates to a process for the preparation of (1S,4R)-4-amino-2-cyclopentene-1-methanol of Formula IIIa. The present invention also specifically relates to process for the preparation of Abacavir sulfate of Formula II using compound of Formula IIIa prepared according to the process of the present invention.

Enantioselective synthesis of the carbocyclic nucleoside (-)-abacavir

An enantiopure β-lactam with a suitably disposed electron withdrawing group on nitrogen, participated in a π-allylpalladium mediated reaction with 2,6-dichloropurine tetrabutylammonium salt to afford an advanced cis-1,4-substituted cyclopentenoid with both high regio- and stereoselectivity. This advanced intermediate was successfully manipulated to the total synthesis of (-)-Abacavir.

Novel salts of (1S,4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol

The present invention relates to novel salts of (1S,4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1 -methanol of Formula I or solvates or hydrates thereof, wherein M represents hemimalonate, malonate, hemioxalate, oxalate, hydrobromide, dihydrobromide, hemimaleate, maleate.

Process for the Preparation of Abacavir

Process for removal of the amino protective group of a N-acylated [(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-cyclopent-2-enyl]methanol of formula (II) where R═H or a (C1-C4)-alkyl, using an inorganic base in a mixture of water and alcohol, to yield abacavir or its salts. The process proceeds very fast and the product can be obtained in high yield and purity.

PREPARATION OF SYNTHETIC NUCLEOSIDES VIA π-ALLYL TRANSITION METAL COMPLEX FORMATION

This invention provides highly regioselective and stereoselective processes for preparing synthetic nucleosides. A process for the preparation of synthetic nucleosides is provided that comprises a) preparing a bicycloamide derivative, b) reacting the bicycloamide derivative with a nucleic acid base or heterocyclic base or salt thereof in the presence of a transition metal catalyst to form a cyclopentenecarboxamide, and c) cleaving a carboxamide group from the cyclopentenecarboxamide to form the synthetic nucleoside. The processes according to the invention can be used for the synthesis of a variety of anti-viral agents, including Abacavir, Carbovir, and Entecavir, as well as derivatives thereof.

Process for the preparation of abacavir

Process for the preparation of abacavir starting from compound of formula (IV) where R1 is a (C1-C4)-alkyl radical comprising first reacting said compound (IV) with anhydrous hydrochloric acid/(C1-C6)-alcohol, and then with tri(C1-C4)-alkyl orthoformate, in the absence of water, followed by reacting the compound obtained with cyclopropylamine and hydrolysing the compound obtained to yield abacavir or its salts.