Chemical development of MDL 103371: An N-methyl-D-aspartate-type glycine receptor antagonist for the treatment of stroke

Organic Process Research and Development

Volumn 4, Issue 6, 2000, Pages 477-487

  Watson, Timothy J N ^a,b   Horgan, Stephen W ^a   Shah, Ramnik S ^a   Farr, Robert A ^a   Schnettler, Richard A ^a   Nevill Jr , C Richard ^a   Weiberth, Franz J ^a   Huber, Edward W ^a   Baron, Bruce M ^a   Webster, Mark E ^a,c   Mishra, Rajesh K ^a,c   Harrison, Boyd L ^a,b   Nyce, Phillip L ^a,d   Rand, Cynthia L ^a,e   Goralski, Christian T ^a,e  

^a Building 51   (United States)

^b PFIZER INC   (United States)

^c PROCTER AND GAMBLE COMPANY   (United States)

^d VERTEX PHARMACEUTICALS   (United States)

^e DOW CHEMICAL COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0034345892     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op000286s     Document Type: Article

References (38)

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27. -1) at predetermined intervals (typically every 0.5-2 min) for the duration of the reaction. The set of absorbance spectra was then plotted as a function of time to generate a ReactIR 3D Plot profile for each reaction sequence, (b) Second, each ReactIR 3D Plot that was generated was then analyzed using ConcIRT, a post-experiment algorithm which tracks changes in absorbance profiles that occur over time as a reaction proceeds. Even with complex reaction mixtures that have overlapping IR bands, ConcIRT has the capability of "extracting" absorption bands of the individual species in a reaction mixture, and thus can provide the individual IR spectrum for each "identified" component, along with the corresponding reaction concentration profiles.
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33. 4-metal salts systems see: He, Y.; Zhao, H.; Pan, X.; Wang, S. Synth. Commun. 1989, 19, 3047 and references therein.
34. The solubility of 6 in methanol was not checked due to concerns of transesterification.
35. Adger, B. M.; Young, R. G. Tetrahedron Lett. 1984, 25, 5219. The use of Raney nickel with hydrazine affords concomitant reduction of the nitrile to the corresponding amine but leaves aromatic bromides and chlorides unchanged (also see: Leggetter, B. E.; Brown, R. K. Can. J. Chem. 1960, 38, 2363).
36. Adger, B. M.; Young, R. G. Tetrahedron Lett. 1984, 25, 5219. The use of Raney nickel with hydrazine affords concomitant reduction of the nitrile to the corresponding amine but leaves aromatic bromides and chlorides unchanged (also see: Leggetter, B. E.; Brown, R. K. Can. J. Chem. 1960, 38, 2363).
37. 3N.
38. The des-chloro isomer was isolated by preparative chromatography and characterized to be the following structure. The other possible des-chloro isomers were not detected with LC/MS techniques. (formula presented).