- A new synthetic approach to 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) derivatives via a [2 + 2 + 2] cycloaddition reaction
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Tetrahydroisoquinoline-3-carboxylic acid derivatives are prepared via a [2 + 2 + 2] cycloaddition reaction as a key step using Wilkinson's and CpCo(CO)2 catalysts. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Kotha, Sambasivarao,Sreenivasachary, Nampally
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- An uncatalyzed cyclo-elimination process for the release of N3- alkylated hydantoins from solid-phase: Synthesis of novel isoxazoloimidazolidinediones
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Solid-phase regioselective nitrile oxide 1,3-dipolar cycloaddition to an ω-alkynyl ester followed by reductive α-N-alkylation and isocyanate α-N- acylation delivers I and sets the stage for the uncatalyzed carbanilide cycloelimination of isoxazoloimidazolidinedione heterocycles (I → II). This traceless release step is induced by simply warming the urea ester intermediate, but requires that the N3 of the nascent hydantoin be fully substituted (I → II; R(c) ≠ H).
- Park, Kyung-Ho,Kurth, Mark J.
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- PROCESS FOR THE PREPARATION OF OMARIGLIPTIN
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The present invention provides a process for preparing omarigliptin.
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Page/Page column 17
(2017/06/23)
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- Evolution of a Manufacturing Route to Omarigliptin, A Long-Acting DPP-4 Inhibitor for the Treatment of Type 2 Diabetes
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Development of a convergent synthesis of omarigliptin (MK-3102) suitable for commercial manufacture is described. The target molecule is assembled through a diastereoselective reductive amination of a highly functionalized pyranone with a mesylated pyrazole followed by deprotection of a Boc group. The synthesis of the pyranone relies on three Ru-catalyzed reactions: (1) a DKR reduction of a rac-α-aminoketone to set the two contiguous stereogenic centers, (2) a cycloisomerization of a bis-homopropargylic alcohol to a dihydropyran, and, finally, (3) a Ru-catalyzed oxidation of a pyranol to the desired pyranone. The regioselective synthesis of a N-Boc-1-mesyl pyrazole fragment was achieved via base-promoted mesyl group isomerization to afford 30:1 selectivity. A highlight of the endgame process development is telescoping a Boc deprotection and reductive amination followed by direct crystallization of the penultimate from the reaction mixture. This avoids handling of an unstable, mutagenic 1-mesylpyrazole BSA salt used in the earlier multikilogram deliveries and improves the overall diastereoselectivity and efficiency of the route.
- Chung, John Y. L.,Scott, Jeremy P.,Anderson, Camille,Bishop, Brian,Bremeyer, Nadine,Cao, Yang,Chen, Qinghao,Dunn, Robert,Kassim, Amude,Lieberman, David,Moment, Aaron J.,Sheen, Faye,Zacuto, Michael
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p. 1760 - 1768
(2015/12/01)
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- Asymmetric synthesis of highly functionalized tetrahydropyran DPP-4 inhibitor
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A practical synthesis of a highly functionalized tetrahydropyran DPP-4 inhibitor is described. The asymmetric synthesis relies on three back-to-back Ru-catalyzed reactions. A Ru-catalyzed dynamic kinetic resolution (DKR) reduction establishes two contiguous stereogenic centers in one operation. A unique dihydropyran ring is efficiently constructed through a preferred Ru-catalyzed cycloisomerization. Hydroboration followed by a Ru-catalyzed oxidation affords the desired functionalized pyranone core scaffold. Finally, stereoselective reductive amination and subsequent acidic deprotection afford the desired, potent DPP-4 inhibitor in 25% overall yield. (Chemical Equation Presented).
- Xu, Feng,Zacuto, Michael J.,Kohmura, Yoshinori,Rosen, Jon,Gibb, Andrew,Alam, Mahbub,Scott, Jeremy,Tschaen, David
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supporting information
p. 5422 - 5425
(2015/02/19)
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- Process for preparing Chiral Dipeptidyl Peptidase -IV Inhibitor Intermediates
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A novel process is provided for the preparation of chiral trans-2,3-disubstituted 5-oxotetrahydropyrans of structural formula (I): wherein Ar is optionally substituted phenyl and P is a primary amine protecting group. These compounds are useful in the synthesis of dipeptidyl peptidase-IV inhibitors for the treatment of Type 2 diabetes. Also provided are useful intermediates obtained from the process.
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Page/Page column 7
(2009/07/25)
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- Synthesis of novel quinone-amino acid hybrids via cross-enyne metathesis and Diels-Alder reaction as key steps
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A "Building Block Approach" for the synthesis of various quinone-amino acid hybrids through ethylene cross-enyne metathesis and Diels-Alder reaction as key steps is described. A library of comformationally constrained quinone-based phenylalanine derivativ
- Kotha, Sambasivarao,Mandal, Kalyaneswar,Banerjee, Shaibal,Mobin, Shaikh M.
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p. 1244 - 1255
(2008/09/17)
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- Highly enantioselective alkylation of glycine methyl and ethyl ester derivatives under phase-transfer conditions: Its synthetic advantage
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Phase-transfer alkylation of the benzophenone Schiff base of glycine methyl or ethyl ester (2) was found to be catalyzed by 3,4,5-F 3-C6H2-NAS-Br [(S,S)-1] with high efficiency and excellent enantioselectivity. This procedure allows facile derivatization of the resulting alkylation products to other synthetically useful chiral building blocks.
- Ooi, Takashi,Uematsu, Yukitaka,Maruoka, Keiji
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p. 1675 - 1678
(2007/10/03)
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- Synthesis of highly functionalized phenylalanine derivatives via cross-enyne metathesis reactions
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A new method for the synthesis of constrained phenylalanine derivatives is described. In this regard, the simple synthesis of acyclic diene building blocks embodying an α-amino acid moiety has been achieved. The diene building blocks have been prepared by cross enyne-metathesis reaction as a key step. The Diels-Alder reaction of the dienes with a dienophile such as dimethyl acetylenedicarboxilate (DMAD) followed by oxidation of the resulting cycloadduct gave highly substituted phenylalanine derivatives.
- Kotha, Sambasivarao,Halder, Somnath,Brahmachary, Enugurthi
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p. 9203 - 9208
(2007/10/03)
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- Constrained phenylalanine derivatives by enyne metathesis and Diels-Alder reaction
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A conceptually new approach for the synthesis of indane-based α-amino acid derivatives is reported. In this regard, the synthesis of five-membered exocyclic and five-membered inner-outer ring diene building blocks (7 and 15) containing α-amino acid moieties is described. Diene 15 is prepared by an enyne metathesis reaction as a key step. In this paper, a full account of our work regarding the Diels-Alder reaction of these dienes with various dienophiles, and the subsequent oxidation of the cycloadducts to give various indane-based α-amino acid derivatives is reported.
- Kotha, Sambasivarao,Sreenivasachary, Nampally,Brahmachary, Enugurthi
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p. 787 - 792
(2007/10/03)
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- A new synthetic approach to 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) derivatives via enyne metathesis and the Diels-Alder reaction
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Various substituted 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) derivatives are synthesized via enyne metathesis and the Diels-Alder reaction.
- Kotha, Sambasivarao,Sreenivasachary, Nampally
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p. 503 - 504
(2007/10/03)
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- Synthesis of unusual α-amino acid derivatives via cross-enyne metathesis reaction
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Various highly functionalized phenylalanine derivatives are prepared via cross-enyne metathesis and Diels-Alder reaction as key steps.
- Kotha, Sambasivarao,Halder, Somnath,Brahmachary, Enugurthi,Ganesh, Thota
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p. 853 - 855
(2007/10/03)
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- Synthesis of constrained α-amino acid derivatives via enyne metathesis reaction
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Synthesis of a diene building block via enyne metathesis reaction and its usage in the preparation of constrained α-amino acid derivatives is described.
- Kotha, Sambasivarao,Sreenivasachary, Nampally,Brahmachary, Enugurthi
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p. 2805 - 2808
(2007/10/03)
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- Ethyl N-(diphenylmethylene)glycinate as anionic glycine equivalent. Monoalkylation, dialkylation and michael additions under solid-liquid phase-transfer catalysis
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Ethyl N-(diphenylmethylene)glycinate, 1, undergoes monoalkylations, dialkylations and Michael additions to ethylenic and acetylenic acceptors under appropriate solid-liquid phase transfer catalysis conditions. Further transformations of the α-disubstituted ketimines lead to α-alkylated aspartic and glutamic acid derivatives 10, 15, 19 and 26, to bicyclic amino acids or derivatives featuring pyrazolone and isoxazolone moieties 30 and 33, and to α-substituted (E)-3,4-dehydroglutamic acids. Copyright
- Lopez, Anna,Moreno-Manas, Marcial,Pleixats, Roser,Roglans, Anna,Ezquerra, Jesus,Pedregal, Concepcion
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p. 8365 - 8386
(2007/10/03)
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- Ethyl N-(Diphenylmethylene)glycinate as Anionic Glycine Equivalent Transition Metal Mediated Preparation of Bicyclic and Tricyclic α,α-Disubstituted α-Amino Acids and Derivatives
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Synthetic approaches to bicyclic and tricyclic α,α-disubstituted α-amino acids and derivatives 6, 8, 10, 12, 13, 21, 22, 23, 24, 28, 30, and 31 are presented.Methyl acetoacetate, ethyl nitroacetate, and ethyl N-(diphenylmethylene)glycinate are compared as
- Moreno-Manas, Marcial,Pleixats, Roser,Roglans, Anna
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p. 1807 - 1814
(2007/10/03)
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- Synthesis of α-substituted and α,α-disubstituted α-amino acids by controlled mono- and dialkylation of ethyl N-diphenylmethyleneglycinate
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Ethyl N-diphenylmethyleneglycinate reacts with one equivalent of alkylating agents in the presence of powdered potassium carbonate to afford, after hydrolysis, monoalkylated glycine esters. A similar process using two equivalents of alkylating agents in t
- Ezquerra,Pedregal,Moreno-Manas,Pleixats,Roglans
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p. 8535 - 8538
(2007/10/02)
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