171922-16-0Relevant articles and documents
A new synthetic approach to 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) derivatives via a [2 + 2 + 2] cycloaddition reaction
Kotha, Sambasivarao,Sreenivasachary, Nampally
, p. 1413 - 1415 (2000)
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.
An uncatalyzed cyclo-elimination process for the release of N3- alkylated hydantoins from solid-phase: Synthesis of novel isoxazoloimidazolidinediones
Park, Kyung-Ho,Kurth, Mark J.
, p. 5841 - 5844 (1999)
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).
PROCESS FOR THE PREPARATION OF OMARIGLIPTIN
-
Page/Page column 17, (2017/06/23)
The present invention provides a process for preparing omarigliptin.
Evolution of a Manufacturing Route to Omarigliptin, A Long-Acting DPP-4 Inhibitor for the Treatment of Type 2 Diabetes
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
, p. 1760 - 1768 (2015/12/01)
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.
Asymmetric synthesis of highly functionalized tetrahydropyran DPP-4 inhibitor
Xu, Feng,Zacuto, Michael J.,Kohmura, Yoshinori,Rosen, Jon,Gibb, Andrew,Alam, Mahbub,Scott, Jeremy,Tschaen, David
supporting information, p. 5422 - 5425 (2015/02/19)
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).
Process for preparing Chiral Dipeptidyl Peptidase -IV Inhibitor Intermediates
-
Page/Page column 7, (2009/07/25)
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.
Synthesis of novel quinone-amino acid hybrids via cross-enyne metathesis and Diels-Alder reaction as key steps
Kotha, Sambasivarao,Mandal, Kalyaneswar,Banerjee, Shaibal,Mobin, Shaikh M.
, p. 1244 - 1255 (2008/09/17)
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
Highly enantioselective alkylation of glycine methyl and ethyl ester derivatives under phase-transfer conditions: Its synthetic advantage
Ooi, Takashi,Uematsu, Yukitaka,Maruoka, Keiji
, p. 1675 - 1678 (2007/10/03)
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.
Synthesis of highly functionalized phenylalanine derivatives via cross-enyne metathesis reactions
Kotha, Sambasivarao,Halder, Somnath,Brahmachary, Enugurthi
, p. 9203 - 9208 (2007/10/03)
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.
Constrained phenylalanine derivatives by enyne metathesis and Diels-Alder reaction
Kotha, Sambasivarao,Sreenivasachary, Nampally,Brahmachary, Enugurthi
, p. 787 - 792 (2007/10/03)
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.
