312904-12-4

Upstream product

• 107-11-9 1-amino-2-propene 
• 204254-96-6 (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester 
• 312904-11-3 ethyl (3R,4S,5R)-5-N-allyllamino-3-(1-ethylpropoxy)-4-hydroxy-1-cyclohexene-1-carboxylate 
• 877238-95-4 (3aR,7R,7aS)-7-amino-2,2-diethyl-3a,6,7,7a-tetrahydro-benzo[1,3]dioxole-5-carboxylic acid ethyl ester 
• 1233402-45-3 C₁₄H₂₃NO₆ 
• 1233402-38-4 C₁₄H₂₄O₅ 
• 1233402-37-3 C₂₁H₃₄O₈ 
• 1233402-36-2 C₁₅H₂₆O₆ 
• 1233402-34-0 C₁₀H₁₈O₅ 
• 1233402-33-9 C₁₀H₁₆O₆ 
• 1257984-90-9 C₂₂H₃₆O₈ 
• 1257984-89-6 C₁₅H₂₆O₅ 
• 25636-49-1 3,3-dimethoxypentane 

Downstream Products

• 332047-17-3 ethyl (3R,4S,5R)-5-N-benzylideneamino-3-(1-ethylpropoxy)-4-hydroxy-1-cyclohexene-1-carboxylate 
• 332047-22-0 ethyl (3R,4S,5R)-5-N-formylamino-3-(1-ethylpropoxy)-4-hydroxy-1-cyclohexene-1-carboxylate 
• 196618-13-0 oseltamivir 
• 312904-15-7 ethyl (3R,4R,5S)-5-N-allylamino-4-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate 
• 332047-18-4 ethyl (3R,4S,5R)-5-N-benzylideneamino-3-(1-ethylpropoxy)-4-methanesulfonyloxy-1-cyclohexene-1-carboxylate 
• 312904-18-0 ethyl (3R,4R,5S)-4-N-acetylamino-5-N-allylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate 
• 312904-17-9 ethyl (3R,4S,5R)-5-amino-3-(1-ethylpropoxy)-4-methanesulfonyloxy-1-cyclohexene-1-carboxylate 
• 877238-97-6 ethyl (3R,4S,5R)-3-(1-ethylpropoxy)-5-N-formylamino-4-methanesulfonyloxy-1-cyclohexene-1-carboxylate 

Relevant academic research and scientific papers

Preparation method of oseltamivir

The invention discloses a preparation method of oseltamivir. The preparation method comprises the steps: taking (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester as a raw material; carrying out a ring-opening reaction with benzylamine, carrying out catalytic hydrogenation debenzylation protection, carrying out Boc-protected N-acylation, carrying out an O-sulfonylation reaction with substituted sulfonyl chloride or trifluoromethanesulfonic anhydride, and carrying out a substitution reaction with benzylamine; carrying out catalytic hydrogenation debenzylation protection and O-acetylation reaction again; and finally removing Boc protection under an acidic condition to prepare oseltamivir. The preparation process is simple, low in cost and suitable for process amplification preparation to meet industrial production of oseltamivir raw drugs.

NITRO GROUP-CONTAINING ETHER COMPOUND AND METHOD FOR PRODUCING SAME

It is possible to produce oseltamivir safely and stably in large quantities by using as a starting material tartaric acid, mannitol or arabinose, via nitro group-containing ether compound of the formula (1). (wherein R1, R2 and Rsup

Process for the preparation of 4,5-diamino shikimic acid derivatives

The present invention relates to a process for the preparation of a 4,5-diamino shikimic acid derivative of formula and pharmaceutically acceptable addition salts thereof wherein R1, R1′ are independent of each other H or alkyl, R2 is an alkyl and R3, R4 are independent of each other H or an alkanoyl, with the proviso that not both R3 and R4 are H. 4,5-diamino shikimic acid derivatives of formula I, especially the (3R,4R,5S)-5-amino-4-acetylamino-3-(1-ethyl-propoxy)-cyclohex-1-ene-carboxylic acid ethyl ester and its pharmaceutically acceptable additional salts are potent inhibitors of viral neuraminidase.

The synthetic development of the anti-influenza neuraminidase inhibitor oseltamivir phosphate (Tamiflu): A challenge for synthesis & process research

The evolution of the synthesis of oseltamivir phosphate (Tamiflu), used for the oral treatment and prevention of influenza virus infections (viral flu) is described. Oseltamivir phosphate is the ethyl ester prodrug of the corresponding acid, a potent and selective inhibitor of influenza neuraminidase. The discovery chemistry route and scalable routes used for kilo laboratory production as well as the technical access to oseltamivir phosphate from (-)-shikimic acid proceeding via a synthetically well-developed epoxide building block followed by azide transformations are reviewed. Synthesis and process research investigations towards azide-free conversions of the key epoxide building block to oseltamivir phosphate are discussed. The search for new routes to oseltamivir phosphate independent of shikimic acid including Diels-Alder approaches and transformations of aromatic rings employing a desymmetrization concept are presented in view of large-scale production requirements.

Process for preparing 1,2-diamino compounds

The invention provides a multistep process for preparing 1,2-diamino compounds and pharmaceutically acceptable addition salts thereof from 1,2-epoxides.

New, azide-free transformation of epoxides into 1,2-diamino compounds: Synthesis of the anti-influenza neuraminidase inhibitor oseltamivir phosphate (Tamiflu)

A new, azide-free transformation of the key precursor epoxide 6 to the influenza neuraminidase inhibitor prodrug oseltamivir phosphate (1, Tamiflu) is described. This sequence represents a new and efficient transformation of an epoxide into a 1,2-diamino compound devoid of potentially toxic and hazardous azide reagents and intermediates and avoids reduction and hydrogenation conditions. Using catalytic MgBr2·OEt2 as a new, inexpensive Lewis acid, the introduction of the first amino function was accomplished by opening of the oxirane ring with allylamine followed by Pd/C-catalyzed deallylation to the amino alcohol 16. The introduction of the second amino group was then accomplished via an efficient reaction cascade involving a domino sequence preferably utilizing a transient imino protection. Selective acetylation of the resulting diamine 17 was achieved under acidic conditions providing the crystalline 4-acetamido-5-N-allylamino-derivative 18, which upon deallylation over Pd/C and phosphate salt formation afforded drug substance 1. The overall yield of this route from 6 of 35-38% exceeds the yield of the azide-based process (27-29%) and does not require any chromatographic purification.