- Preparation method of posaconazole intermediate
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The invention relates to the technical field of medicine preparation, and especially relates to a preparation method of a posaconazole intermediate. The preparation method comprises the following steps: reacting a compound as shown in a formula II, serving as a raw material, with 1, 2, 4-triazole to obtain a compound as shown in a formula III, and then reacting with air or oxygen under the action of a catalyst 1 to obtain a compound as shown in a formula IV; reacting the compound as shown in the formula IV with dimethyl malonate to obtain a compound as shown in a formula V; reacting the compound shown in the formula V under the action of a reducing agent to obtain a compound shown in a formula VI; and finally, carrying out intramolecular etherification reaction on the compound shown in the formula VI, and carrying out sulfonylation reaction on the obtained product to obtain a target product I. The method has the advantages of cheap and easily available raw materials, mild reaction conditions, few reaction steps, high yield and high purity of the obtained product.
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- POSACONAZOLE, COMPOSITION, INTERMEDIATE, PREPARATION METHOD THEREFOR, AND USES THEREOF
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The present invention relates to a compound of formula III, wherein, R is selected from the group consisting of C1-C4 alkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted benzyl, preferably isopropyl; and two Ar groups may be the same or different, and are each independently selected from the group consisting of substituted or unsubstituted aryl groups, preferably substituted or unsubstituted phenyl, such as p-methoxyphenyl and the like, wherein the compound is preferably in a solid form.
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Paragraph 0246-0247
(2019/03/14)
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- Preparation method for preparing posaconazole midbody
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The invention provides a method for preparing a posaconazole midbody shown as the formula 1. According to the preparation method, a compound 2 reported in literature is used as a raw material; firstly, trialkyl silane is used for protecting hydroxyl to obtain a compound 3; then, the compound 3 takes a reaction with sodium salts 4 of triazole to obtain a compound 5; next, siloxane removal is performed under the effects of paratoluensulfonyl chloride and alkali, and toluenesulfonyl protection is performed to obtain a compound 1. The method provided by the invention can overcome the defects in the prior art; a splicing step is not performed; the occurrence of side reaction and the appearance of impurities are reduced; the reaction selectivity and the yield are improved. The formulas are shown as the accompanying drawing.
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- IMPROVED PROCESS FOR THE PREPARATION OF ((3S,5R)-5-((1H-1,2,4-TRIAZOL-1-YL)METHYL)-5-(2,4-DIFLUOROPHENYL)TETRAHYDROFURAN-3-YL)METHYL-4-METHYLBENZENESULFONATE
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The present invention relates to process for the preparation of ((3S,5R)-5-((lH-l,2,4- triazol- 1 -yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methyl-4-methylbenzene sulfonate compound of formula- 1 through novel intermediates. Further the said compound of formula- 1 is useful as a key intermediate for the preparation of Posaconazole.
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Page/Page column 22
(2015/05/06)
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- Process for the Preparation of Triazole Antifungal Drug, Its Intermediates and Polymorphs Thereof
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A process for the preparation of 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)tetrahydro-5-(1H-1,2,4-triazol-1-ylmethyl)-3-furanyl]methoxy]phenyl]-1-piperazinyl]phenyl]-2-[(1S,2S)-1-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one compound of formula-1, its intermediates and polymorphs thereof. (I)
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Paragraph 0322; 0323
(2014/12/09)
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- PROCESS FOR THE PREPARATION OF A CHIRAL COMPOUND
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The present invention relates to a process for the preparation of a compound of formula (V), in particular posaconazole, wherein said process comprises the steps of (1) providing a mixture comprising a compound of formula (IV), a protic solvent system, and a suitable base; and (2) heating the mixture of (1) to obtain a mixture comprising the compound of formula (V).
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- PROCESS FOR THE PREPARATION OF CHIRAL TRIAZOLONES
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A process for the preparation of a chiral compound, in particular posaconazole, wherein the process comprises mixing and reacting the compounds of formula (I) Y3-NH2; of formula (Ila) 0=C=N-Y0 and/or of formula (lIb) and of formula (III) in a solvent in any order to obtain a reaction mixture containing a chiral compound of formula (IV) and/or formula (V).
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- Concise asymmetric routes to 2,2,4-trisubstituted tetrahydrofurans via chiral titanium imide enolates: Key intermediates towards synthesis of highly active azole antifungals Sch 51048 and Sch 56592
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Two complimentary approaches to the key (-)-(2R)-cis-tosylate 1 and its (+)-(2S)-enantiomer 15 via generation of chiral imide enolates having a 2,2-disubstituted olefin functionality in the β-position, are described. In a 'protecting group free' sequence, reaction of the titanium enolate generated from (4R)-benzyl-2-oxazolidinone derived imide 5b with s-trioxane provided a convenient intermediate 19 which could be directly subjected to 2,4-diastereoselective iodocyclization.
- Saksena, Anil K.,Girijavallabhan, Viyyoor M.,Wang, Haiyan,Liu, Yi-Tsung,Pike, Russell E.,Ganguly, Ashit K.
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p. 5657 - 5660
(2007/10/03)
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- HIGHLY STEREOSELECTIVE ACCESS TO NOVEL 2,2,4-TRISUBSTITUTED TETRAHYDROFURANS BY HALOCYCLIZATION: PRACTICAL CHEMOENZYMATIC SYNTHESIS OF SCH 51048, A BROAD-SPECTRUM ORALLY ACTIVE ANTIFUNGAL AGENT
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A convenient synthesis of (-)-(2R)-cis-tosylate 2 is reported via stereoselective 5-exo iodocyclization of the optically active 2,2-disubstituted olefin 9a.Enzymatic desymmetrization of the homoallylic diol 4 with Novo SP435 allowed optimal pro-(S) selectivity to provide the desired (-)-(S)-monoacetate 9a.Under the irreversible reaction conditions, the presence of a bulky aryl substituent on the 2,2-disubstituted olefin seems to determine stereochemical outcome of these halocyclizations.
- Saksena, Anil K.,Girijavallabhan, Viyyoor M.,Lovey, Raymond G.,Pike, Russell E.,Wang, Haiyan,et al.
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p. 1787 - 1790
(2007/10/02)
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- PPL-catalyzed enzymatic asymmetrization of a 2-substituted prochiral 1,3-diol with remote chiral functionality: Improvements toward synthesis of the eutomers of SCH 45012
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Porcine pancreatic lipase (PPL) catalysis has been used to establish both stereocenters of the cis-(tetrahydrofuranylmethyl) tosylate 4. In addition to the enzymatic differentiation of the hydroxyl groups of the pro-chiral 1,3-diol segment of 2, successful enzymatic resolution of the racemic diol 10 provided an alternate route to the important precursor 1.
- Lovey, Raymond G.,Saksena, Anil K.,Girijavallabhan, Viyyoor M.
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p. 6047 - 6050
(2007/10/02)
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