66414-17-3Relevant 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.
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
