145012-50-6Relevant academic research and scientific papers
Synthesis of a bicyclic piperazine from l-aspartic acid and application of a fluoride-promoted SNAr coupling
Sieser, Janice E.,Singer, Robert A.,McKinley, Jason D.,Bourassa, Dennis E.,Teixeira, John J.,Long, James
, p. 1328 - 1335 (2012/01/12)
The process development is reported of a pivotal C-N bond formation involving ((7R,9aS)-octahydro-1H-pyrido[1,2-a]pyrazin-7-yl)methanol (2) undergoing nucleophilic aromatic substitution with 3-chlorobenzo[d]isoxazole (3) to furnish ((7R,9aS)-2-(benzo[d]isoxazol-3-yl)octahydro-1H-pyrido[1,2-a] pyrazin-7-yl)methanol (4) as a key intermediate for a family of compounds (1). Essential to the success of the coupling is the use of fluoride in combination with a phase transfer catalyst. The development of an alternative route to bicyclic piperazine 2 that uses l-aspartic acid (20) as a starting material to avoid the need for a classical salt resolution is described.
New entries in Lewis acid-Lewis base bifunctional asymmetric catalyst: Catalytic enantioselective Reissert reaction of pyridine derivatives
Ichikawa, Eiko,Suzuki, Masato,Yabu, Kazuo,Albert, Matthias,Kanai, Motomu,Shibasaki, Masakatsu
, p. 11808 - 11809 (2007/10/03)
The first catalytic enantioselective Reissert reaction of pyridine derivatives that affords products with excellent regio- and enantioselectivity is described. The key for success is the development of new Lewis acid-Lewis base bifunctional asymmetric catalysts containing an aluminum as a Lewis acid and sulfoxides or phosphine sulfides as a Lewis base. These reactions are useful for the synthesis of a variety of chiral piperidine subunits, and catalytic enantioselective formal synthesis of CP-293,019, a selective D4 receptor antagonist, was achieved. Preliminary mechanistic studies indicated that both sulfoxides and phosphine sulfides can activate TMSCN as a Lewis base. In addition, the sulfoxides with appropriate stereochemistry might stabilize a highly enantioselective bimetallic complex (a presumed active catalyst) through internal coordination to aluminum. Copyright
Resolution of trans-7-(hydroxy-methyl)octahydro-2H-pyrido-1,2a)pyrazine
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, (2008/06/13)
The invention provides a process for the optical resolution of a racemic mixture, or an optically enriched mixture, of trans-7-(hydroxymethyl)octa-hydro-2H-pyrido-1,2a)pyrazine, a key intermediate for preparing pharmacologically active 2,7-substituted octahydro-1H-pyrido[1,2-a]pyrazine derivatives useful in the treatment of disorders of the dopamine system. The process of the invention involves use of D-(?) or L-(+)naproxen as a resolving agent.
Process and intermediates for bis-aza-bicyclic anxiolytic agents
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, (2008/06/13)
Optically pure intermediates of formula (1) wherein the substituent B is either cis or trans to the C9a -C1 bond and is selected from the group consisting of --CH2 OH, --CHO, --CH2 OSO2 R, --CH2 CN, --CH(OH)CH2 NO2, --CH=CH--NO2, (2) and (3), C is selected from the group consisting of --H, (4), (5), and a nitrogen protecting group which is removable by hydrogenation or acid treatment; and wherein R is (C1 -C8) alkyl, phenyl or alkyl substituted phenyl; X is N or CH; Y is O or S and Z is H or Cl; for the synthesis of octahydro-1H-pyrido(1,2-a)pyrazinyl ethyl carboxamide anxiolytic agents.
2,7-SUBSTITUTED OCTAHYDRO-1H-PYRIDO[1,2-A]PYRAZINE DERIVATIVES
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, (2008/06/13)
Substituted pydrido[1,2-a]pyrazines of general formula I wherein Ar and Ar 1 represent various carbocyclic and heterocyclic aromatic rings; A represents O, S, SO, SO 2, C=O, CHOH, or--(CR. sup.3 R. sup.4) and n is 0-2 as well as precursors thereto are ligands for dopamine receptor subtypes within the body and are therefore useful in the treatment of disorders of the dopamine system. STR1
Synthesis, SAR and pharmacology of CP-293,019: A potent, selective dopamine D4 receptor antagonist
Sanner, Mark A.,Chappie, Thomas A.,Dunaiskis, Audrey R.,Fliri, Anton F.,Desai, Kishor A.,Zorn, Stevin H.,Jackson, Elisa R.,Johnson, Celeste G.,Morrone, Jean M.,Seymour, Patricia A.,Majchrzak, Mark J.,Faraci, W. Stephen,Collins, Judith L.,Duignan, David B.,Di Prete, Cecilia C.,Lee, Jae S.,Trozzi, Angela
, p. 725 - 730 (2007/10/03)
A series of novel, potent and selective pyrido[1,2-a]pyrazine dopamine D4 receptor antagonists are reported including CP-293,019 (D4 K(i) = 3.4 nM, D2 K(i) > 3,310 nM), which also inhibits apomorphine-induced hyperlocomotion in rats after oral dosing.
Synthesis of trans-7-Hydroxymethyl-2-(2-benzisoxazol-3-yl)octahydro-2H-pyridopyrazine
Urban, Frank J.
, p. 857 - 862 (2007/10/02)
An efficient synthesis of trans-7-hydroxymethyl-2-(2-benzisoxazol-3-yl)octahydro-2H-pyridopyrazine 2 is presented which relies on the equilibration of cis-dimethyl piperidinedicarboxylate followed by alkylation with phthalimidoethyl triflate.
Synthesis of an Optically Active Octahydro-2H-pyridopyrazine Based CNS Agent
Urban, Frank J.,Breitenbach, Ralph,Murtiashaw, Charles W.,Vanderplas, Brian C.
, p. 321 - 324 (2007/10/02)
A synthesis of an optically active octahydro-2H-pyridopyrazine is presented.The key sequence involved the equilibration of an optically active cis-aldehyde to give the thermodynamic transaldehyde that was trapped by nitromethane anion.
Bis-aza-bicyclic anxiolytic agents
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, (2008/06/13)
Anxiolytic agents which are racemic or optically active pyrido[1,2-a]pyrazine derivatives of the formula STR1 wherein x is N or CH and Y represents one of certain pyrazolo, triazolo, tetrazolo or cyclic imido radicals; and intermediates therefor.
