A scaleable synthesis of methyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate

被引：15

作者：

Boros, Eric E. ^{[1
]}

Burova, Svetlana A. ^{[1
]}

Erickson, Greg A. ^{[1
]}

Johns, Brian A. ^{[1
]}

Koble, Cecilia S. ^{[1
]}

Kurose, Noriyuki ^{[1
]}

Sharp, Matthew J. ^{[1
]}

Tabet, Elie A. ^{[1
]}

Thompson, James B. ^{[1
]}

Toczko, Matthew A. ^{[1
]}

机构：

[1] GlaxoSmithKline Res & Dev Ltd, Res Triangle Pk, NC 27709 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2007年 / 11卷 / 05期

关键词：

D O I：

10.1021/op7001326

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A scaleable synthesis of methyl 3-amino-5-(4-fiuorobenzy1)-2-pyridinecarboxylate (1b), starting from 5-bromo-2-methoxypyridine (8) and 4-fluorobenzaidehyde (9), is described. Key steps in the process include lithium-bromine exchange of 8, addition of the resulting lithiate to aldehyde 9, regioselective nitration of pyridone 12, and Pd-catalyzed alkoxycarbonylation of bromopyridine 15b. Overall yield of the five-stage synthesis was 23%; intermediates 10, 12, 13, 15b, and final product 1b center dot HCl were isolated as filterable solids. Compounds 1a,b are important intermediates in the synthesis of 7-benzylnaphthyridinones (e.g., 2) and related HIV-1 integrase inhibitors.

引用

页码：899 / 902

页数：4

共 14 条

[1] SAR study of a subtype selective allosteric potentiator of metabotropic glutamate 2 receptor, N-(4-phenoxyphenyl) N-(3-pyridinylmethyl)ethanesulfonamide [J].

Barda, DA ;

Wang, ZQ ;

Britton, TC ;

Henry, SS ;

Jagdmann, GE ;

Coleman, DS ;

Johnson, MP ;

Andis, SL ;

Schoepp, DD .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (12) :3099-3102

[2] Strong reduction of hydroxylamine accumulation in the catalytic hydrogenation of nitroarenes by vanadium promoters [J].

Baumeister, P ;

Blaser, HU ;

Studer, M .

CATALYSIS LETTERS, 1997, 49 (3-4) :219-222

[3]

BURTON AG, 1971, TETRAHEDRON LETT, V12, P2211

[4] Extended scope of in situ iodotrimethylsilane mediated selective reduction of benzylic alcohols [J].

Cain, GA ;

Holler, ER .

CHEMICAL COMMUNICATIONS, 2001, (13) :1168-1169

[5] Substituted 2-pyridinemethanol derivatives as potent and selective phosphodiesterase-4 inhibitors [J].

Ducharme, Y ;

Friesen, RW ;

Blouin, M ;

Côté, B ;

Dubé, D ;

Ethier, D ;

Frenette, R ;

Laliberté, F ;

Mancini, JA ;

Masson, P ;

Styhler, A ;

Young, RN ;

Girard, Y .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (11) :1923-1926

[6]

Ende DJA, 1998, ORG PROCESS RES DEV, V2, P382

[7]

JOHNS BA, 2000, Patent No. 05077050

[8] Synthesis of azide-fluoro-dehydrocoelenterazine analog as a photoaffinity-labeling probe and photolysis of azide-fluoro-coelenterazine [J].

Kuse, M ;

Doi, I ;

Kondo, N ;

Kageyama, Y ;

Isobe, M .

TETRAHEDRON, 2005, 61 (24) :5754-5762

[9] Bicyclo[3.1.0]hexyl urea melanin concentrating hormone (MCH) receptor-1 antagonists: Impacting hERG liability via aryl modifications [J].

McBriar, Mark D. ;

Guzik, Henry ;

Shapiro, Sherry ;

Xu, Ruo ;

Paruchova, Jaroslava ;

Clader, John W. ;

O'Neill, Kim ;

Hawes, Brian ;

Sorota, Steve ;

Margulis, Michael ;

Tucker, Kristal ;

Weston, Daniel J. ;

Cox, Kathleen .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (16) :4262-4265

[10]

Murai H., 2004, PCT Int. Appl., Patent No. [WO04/024693, 04024693]

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