66414-18-4Relevant academic research and scientific papers
Identification and development of an efficient route to SB-649915
Armitage, Mark,Bret, Guillaume,Choudary, Bernie M.,Kingswood, Mike,Loft, Mike,Moore, Steve,Smith, Steve,Urquhart, Michael W. J.
, p. 1626 - 1634 (2013/02/22)
The discovery and development of an efficient manufacturing route to the SSRI-5-HT1A receptor antagonist 6-[(1-{2-[(2-methyl-5-quinolinyl)oxy]ethyl}-4- piperidinyl)methyl]-2H-1,4-benzoxazin-3(4H)-one (SB-649915) 1 is described. The existing route to 1 involved coupling quinoline 6 with piperidine 5 and was considered lengthy as a consequence of the nine synthetic steps required to prepare 5. Two new routes to the key piperidine intermediate 5 are identified which deliver this compound in five and two steps respectively, from readily available materials using novel lithiation and Friedel-Crafts methodology respectively. The latter of these two routes was successfully demonstrated at 5 L scale to deliver 700 g of 5. Development to the methanesulfonate 34, an alternative to quinoline 6, is also described as is the final alkylation of piperidine 5 with this methanesulfonate 34 to deliver SB-649915 1.
Lewis acid promoted benzylic cross-couplings of pyridines with aryl bromides
Duez, Stephanie,Steib, Andreas K.,Manolikakes, Sophia M.,Knochel, Paul
supporting information; experimental part, p. 7686 - 7690 (2011/10/17)
Either ZnCl2, Sc(OTf)3, or BF3OEt 2 can promote the palladium-catalyzed arylation of methylpyridines and related heterocycles (see example). The complexation of the Lewis acid to the nitrogen atom in the heteroc
3,4-Dihydro-2H-benzoxazinones are 5-HT1A receptor antagonists with potent 5-HT reuptake inhibitory activity
Atkinson, Peter J.,Bromidge, Steven M.,Duxon, Mark S.,Gaster, Laramie M.,Hadley, Michael S.,Hammond, Beverley,Johnson, Christopher N.,Middlemiss, Derek N.,North, Stephanie E.,Price, Gary W.,Rami, Harshad K.,Riley, Graham J.,Scott, Claire M.,Shaw, Tracey E.,Starr, Kathryn R.,Stemp, Geoffrey,Thewlis, Kevin M.,Thomas, David R.,Thompson, Mervyn,Vong, Antonio K.K.,Watson, Jeannette M.
, p. 737 - 741 (2007/10/03)
Starting from a high throughput screening hit, a series of 3,4-dihydro-2H-benzoxazinones has been identified with both high affinity for the 5-HT1A receptor and potent 5-HT reuptake inhibitory activity. The 5-(2-methyl)quinolinyloxy derivative
Flexible N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogues: Synthesis and monoamine oxidase catalyzed bioactivation
Efange,Michelson,Remmel,Boudreau,Dutta,Freshler
, p. 3133 - 3138 (2007/10/02)
Eighteen analogues of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and evaluated as substrates of monoamine oxidase. In general, the flexible analogues, characterized by the presence of a methylene (or ethylene) bridge between the aryl/heteroaryl and tetrahydropyridyl moieties, were better substrates of the enzyme than the conformationally restricted MPTP. It is suggested that the increased oxidative activity of these flexible analogues reflects enhanced binding due to the ability of the C-4-aryl/heteroaryl substituent to gain access to a hydrophobic pocket within the substrate binding site.
