- Preparation method of rosuvastatin calcium intermediate
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The invention provides a preparation method of a rosuvastatin calcium intermediate. The preparation method of the rosuvastatin calcium intermediate, namely, the compound shown as formula I in the description comprises the following steps: (1) a compound 5 shown as formula II in the description is generated from 4-fluorobenzaldehyde, methyl isobutyrylacetate and urea under the action of a catalyst; (2) a compound 6 shown as formula III in the description is generated from the compound 5 under the action of potassium persulfate as an oxidizing agent; (3) a compound 7 shown as formula IV in the description is generated from the compound 6, tosyl chloride and N-methyl methanesulfonamide under the action of a catalyst; (4) the target compound shown as the formula I is generated from the compound 7 under the action of a vitride solution as a reducing agent and crystallized with a crystallization solution, and a purified target compound is obtained. The preparation method of the rosuvastatin calcium intermediate has the advantages of low production cost, mild condition and simple and convenient operation.
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Paragraph 0004
(2017/10/23)
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- Efficient Construction of the Nucleus of Rosuvastatin Calcium
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A novel and efficient five-step synthetic route, including a Biginelli reaction, dehydrogenation, chlorination, sulfonamidation, and reduction, for the core of Rosuvastatin was established. All steps were systematically studied. Tert-butylhydroperoxide aqueous solution was applied in the dehydrogenation instead of nitric acid. N,N-dimethylaniline was employed as a catalyst to accelerate the chlorination proceeding smoothly, and its catalytic mechanism is discussed. In the sulfonamidation, the conversion of compound 5 was obviously improved by use of NaH and acetonitrile. In addition, two sulfonamidation side products 6 and 7 were detected and isolated. Thus, under the optimized reaction conditions, the target product was obtained in 60.4% total yield, much higher than the reported yield (36.4%).
- Zhou, Yingtao,Lin, Chenhui,Xing, Yuzhi,Chen, Ligong,Yan, Xilong
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p. 1898 - 1903
(2017/05/29)
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- Synthesis, characterization and crystal structure of N-(4-(4-Fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide
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N-[4-(4-Fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl]-N-methylmethane sulfonamide (I), an important intermediate to synthesize rosuvastatin, an HMG-CoA reductase inhibitor. It was prepared from methyl 4-(4-fluorophenyl)-6-isopropyl-2-(methylamino)pyrimidine-5-carboxylate (1) via mesylation by mesyl chloride and sodium tert-pentoxide, then reduction by DIBAL/HCl. The product was characterized by NMR and LC-MS. The crystal structure of compound I was investigated using X-ray diffraction and SHELXTL-97 software. The result indicated that compound I crystallized in the monoclinic system, space group C2/C with a = 29.683(6), b = 7.6290 (15), c = 18.215(4) ?, V = 3451.1 (16) ?3; Z 8.
- Xu, Jia-Ying,Cheng, Wei-Hua,Zhu, Xun,Wu, Huan-Ling,Wang, Kai
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p. 7766 - 7768
(2015/02/19)
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- A PROCESS FOR THE PREPARATION OF INTERMEDIATES OF ROSUVASTATIN
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The present invention provides a process for the preparation of the rosuvastatin intermediates and their conversion to rosuvastatin or its pharmaceutically acceptable salts thereof.
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Page/Page column 8; 16; 20-21
(2008/12/05)
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- PREPARATION OF ALKYL 4-(4-FLUOROPHENYL)-6-ISOPROPYL-2-[METHYL(METHYLSULFONY)AMINO]-PYRIMIDINE-5-CARBOXYLATE AND ITS SUBSEQUENT CONVERSION TO N-[4-(4-FLUOROPHENYL)-5-FORMYL-6-ISOPROPYL PYRIMIDIN-2-YL]-N-METHYLMETHANESULFONAMIDE-A KEY INTERMEDIATE IN THE SYNTHESIS OF ROSUVASTATIN
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The present invention discloses a novel process to prepare a compound of formula (IIA). By reacting a compound of formula-[D], wherein R1 is C1 to C6 alkyl, preferably R1 is methyl or ethyl, more preferably R1 is methyl ; and R2 is C1 to C8 n-alkyl or branched alkyl, cycloalkyl, phenyl , benzyl or substituted phenyl group, preferably R2 is methyl ; with N-methyl methanesulfonamide and a base, optionally with a salt of N-methyl methanesulfonamide, in suitable solvent(s) , to give a compound of formula (IIA), followed by converting compound of formula (IIA) to a compound for formula -[B], by a known process and finally converting a compound of formula (B) to a compound of formula (II), by a novel process using calcium hypochlorite / TEMPO as an oxidant.
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Page/Page column 16
(2008/06/13)
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- METHOD FOR PRODUCING PYRIMIDINE COMPOUND
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Compound (II) and compound (III) are reacted to give compound (IVa) and/or compound (IVb); which are/is then reacted with compound (V) to give compound (I). wherein X is a methylthio group and the like, R1 and R2 are each a lower alkyl group optionally having substituent(s), an aryl group optionally having substituent(s) and the like, R3 is a lower alkyl group, R4 is a hydrogen atom, a lower alkyl group optionally having substituent(s) and the like, and Q is a carboxylate group and the like.
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Page/Page column 16
(2010/11/28)
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- Process for the production of tert-butyl (E)-(6-[2-[4-(-flourophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]vinyl](4R,6S)-2, 2-dimethyl[1, 3]oioxan-4yl)acetace
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The invention concerns a process for the manufacture of tert-butyl (E)-(6-[2-4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]vinyl}-(4R, 6S)-2,2-dimethyl[1,3-dioxan-4-yl) acetate, the novel starting material used in said process and the use of the process in the manufacture of a pharmaceutical.
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- PROCESS FOR THE PREPARATION OF PYRIMIDINE DERIVATIVES
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There is described a process for the preparation of compounds of formula (1) starting from the reaction of the compounds of formulae (24), (25) and (26) to form the compound of formula (23), wherein in each case R1, R2 and R3 are each independently of the others an unsubstituted or substituted organic radical; R4 is hydrogen, unsubstituted or substituted C1-C8alkyl, C1-C8alkoxy, phenoxy or benzyloxy, or halogen; Y1 and Y2 are each independently of the other hydrogen or a protecting group, or Y1 and Y2 together are a protecting bridge; and X1 is hydrogen, an organic radical or a cation; and also novel intermediates.
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- Process for preparing 2-amino-4-(4-fluorphenyl)-6-alkylpyrimidine-5-carboxylate
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A process for the preparation of a compound of the formula: wherein the variables are herein below defined.
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- Crystalline salts of 7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3r,5s)-3,5-dihydroxyhept-6-enoic acid
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The invention relates to crystalline salts of the compound (E)-7-[4-(4-fluorophenyl)-6-iso-propyl-2-[methyl(methyl-sulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid of formula (I),as well as processes for their manufacture, pharmaceutical compositions containing them, and their uses.
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- PROCESS FOR THE PREPARATION OF ROSUVASTATIN
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The present invention relates to a cost effective and industrially advantageous process for the preparation of 4-4(fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulphonylamino)-5-pyrimidinecarboxaldehyde, referred to here as pyrimidine aldehyde of structural Formula I and to the use of this compound as intermediate for the preparation of rosuvastatin.
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Page/Page column 4; 11
(2008/06/13)
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