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A new route of synthesis of the compound Aliskiren of formula (I), used in the treatment of hypertension, is described.

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Compounds of formula (XII), are simultaneously halogenated in the 5 position and hydroxylated in the 4 position under lactonization, the halolactone is reacted with an amine to form a carboxamide, the halogen is replaced with azide, if necessary after the introduction of a hydroxy protecting group, the resulting azide is converted to a lactone, the lactone is amidated and then the azide converted to the amine group, in order to obtain compounds of formula (I) or a salt thereof.

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The present invention relates to a process and intermediates for the manufacture of aliskiren or pharmaceutically acceptable salts thereof.

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N-Acyl-beta-aminoalcohols were obtained efficiently via a highly endocyclic cleavage of N-acyloxazolidinones mediated by sodium azide in methanol at 40C.

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The synthesis of aliskiren (1), a recently marketed drug for the treatment of hypertension, is presented. The focus of our synthetic effort is to develop an efficient pathway for the synthesis of (2S,7R,E)-2-isopropyl-7-(4-methoxy-3-(3-methoxypropoxy) benzyl)-N,N,8-trimethylnon-4-enamide (2a), which has been used as the advanced intermediate toward aliskiren. After an extensive investigation of three different strategies designed to construct the E-olefin functionality in 2a by employing the olefin cross-metathesis, Horner-Wadsworth-Emmons (HWE), and Julia-type olefinations, we have established a new protocol for the synthesis of 2a with a substantially improved overall efficiency in terms of the yield (ca. 33%), and diastereo- and E/Z-selectivity. The key transformations were the Evans chiral auxiliary-aided asymmetric allylation for the synthesis of the appropriate chiral intermediates in excellent enantiomeric purity of higher than 97% ee and a modified Julia-Kocienski olefination for the highly selective construction of E-2a with up to 13.6:1 E/Z ratio from the chiral intermediates. Consequently, the results provide an appealing option for the synthesis of aliskiren. This journal is

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A synthesis of the (-)-dienone 1 (R = Pr(i)) via ring-closing alkene metathesis to give the substituted dihydropyran 13 in the presence of alkenyl iodide functionality is described.

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A novel method for the synthesis of chiral beta3-amino acids is developed where the acid functionality was built by oxidative cleavage of an alpha-allylic group that was introduced by Evans’ asymmetric alkylation of an appropriate acid substrate and the amino part came from the amide of the original carboxyl group following a modified Hofmann rearrangement reaction.

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In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 145589-03-3, name is (R)-4-Benzyl-3-(3-methylbutanoyl)oxazolidin-2-one, introducing its new discovery. Product Details of 145589-03-3

The present invention relates to a novel manufacturing process and novel intermediates useful in the synthesis of pharmaceutically active compounds, especially rennin inhibitors such as Aliskiren. The invention describes a preparation of enantiomerically pure 8-aryloctanoic acids of general formula I from readily available key intermediate, chiral cis-diacid of formula II, aziridine of formula XI and a monocyclic compound of formula III.

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In the present study we wish to report the details of the diastereoselective reactions of titanium enolates derived from N-propionyloxazolidone 1 in inter- and intramolecular Michael reactions with ethyl vinyl ketone, methyl acrylate, and acrylonitrile (eq 1).

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We report a convergent synthesis of the potent orally active non-peptide renin inhibitor CGP60536B. The key reaction employs the coupling of the enantiopure Grignard species derived from chloride 13 with the diastereomerically pure gammalactone 9b. The stereoselective reduction of the resulting ketone 14b has been thoroughly investigated. (C) 2000 Elsevier Science Ltd.

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