194602-25-0Relevant academic research and scientific papers
The discovery and process development of a commercial route to the water soluble prodrug, fosfluconazole
Bentley, Arthur,Butters, Michael,Green, Stuart P.,Learmonth, William J.,MacRae, Julie A.,Morland, Matthew C.,O'Connor, Garry,Skuse, Joanne
, p. 109 - 112 (2002)
A case history detailing the rationale behind the discovery of 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazole-1-yl)-2-propyl dihydrogen phosphate, fosfluconazole (2), a water-soluble prodrug of Diflucan, and the subsequent development of a commercial route is presented. Particular items to note are (i) that this compound was discovered in the Chemical Research and Development Department, hence Chemical Research and Development can play a key role in prodrug discovery, (ii) the strategy behind the selection of phosphate ester promoiety, by phosphorylation of a sterically hindered tertiary alcohol, (iii) the development of the initial route to remove thermally hazardous reagents and to improve processing to allow scale-up, and (iv) the identification and development of the proposed commercial process.
Preparation method of fosfluconazole
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Paragraph 0062, (2020/06/17)
The invention provides a preparation method of fosfluconazole. The method comprises the following steps: preparing fluconazole dichlorophosphate: under the protection of nitrogen, controlling the temperature to be-10 DEG C to 0 DEG C, slowly dropwise adding phosphorus oxychloride into a dichloromethane solution of triethylamine, maintaining the temperature to be-10 DEG C to 0 DEG C, performing stirring for 1 hour, slowly dropwise adding a dichloromethane solution of fluconazole, and monitoring the completion of the reaction by TLC; maintaining temperature between-10 DEG C and 0 DEG C, adding water and stirring for 30 minutes, adding inorganic base until the pH value of the water phase is at least 8; and performing standing stratification, separating out the fluconazole, wherein the organicphase contains the fluconazole dichlorophosphate, the fluconazole is prepared through the fluconazole-fluconazole dichlorophosphate-fluconazole dibenzyl phosphate-fosfluconazole ammonium salt-fosfluconazole process, the yield is increased, all intermediates are controllably prepared, the raw materials can be recycled, and raw material waste and organic waste pollution are reduced.
Synthesizing method for preparing 2,4-difluoro-alpha, alpha-bi(1hydrogen-1,2,4-triazole-1-methyl) benzyl alcohol dibenzyl phosphate
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Paragraph 0008, (2016/11/24)
The invention relates to a medicine midbody preparation method and provides a synthesizing method for preparing 2,4-difluoro-alpha, alpha-bi(1hydrogen-1,2,4-triazole-1-methyl) benzyl alcohol dibenzyl phosphate. An original technology is improved in the method, a fosfluconazole midbody is synthesized through the method by adding the catalytic amount of iodine and changing the feeding sequence, and the yield can reach over 80% and is increased by 10-20% compared with existing literature reports. Use of alkaline in the reaction process is reduced, reaction is more moderate, operation is easy, and reaction cost is lowered.
Triazole derivatives useful in therapy
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, (2008/06/13)
The invention provides compounds of formula 1, R1—OP(O)(OH)2??I wherein R1 represents the non-hydroxy portion of a triazole antifungal compound of the type comprising a tertiary hydroxy group; or a pharmaceutically accepta
