Preparation and Utility of Trihaloethyl Imidates: Useful Reagents for the Synthesis of Amidines

被引：50

作者：

Caron, Stephane ^{[1
]}

Wei, Lulin ^{[1
]}

Douville, Jasmin ^{[1
]}

Ghosh, Arun ^{[1
]}

机构：

[1] Pfizer Global R&D, Chem R&D, Groton, CT 06340 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2010年 / 75卷 / 03期

关键词：

COORDINATION; ACIDITIES; MECHANISM; NITRILES;

D O I：

10.1021/jo902159z

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

2,2,2-Ti-ifluoro- and trichloroethyl imidates, which are easily prepared by reaction of a nitrile and a trihaloethanol in the presence of HCl, have proven to be excellent reagents for the preparation of amidines under mild reaction conditions. Depending on the nature of the ne nucleophile, the imidates call react either as the free-base or the hydrochloride salt in a telescoped process. In several cases, the p-bromobenzoate salt of the desired product was directly isolated from the reaction mixture.

引用

页码：945 / 947

页数：3

共 20 条

[1] Synthesis and pharmacological evaluation of 1-[(1,2-diphenyl-1H-4-imidazolyl)methyl]-4-phenylpiperazines with clozapine-like mixed activities at dopamine D2, serotonin, and GABAA receptors [J].

Asproni, B ;

Pau, A ;

Bitti, M ;

Melosu, M ;

Cerri, R ;

Dazzi, L ;

Seu, E ;

Maciocco, E ;

Sanna, E ;

Busonero, F ;

Talani, G ;

Pusceddu, L ;

Altomare, C ;

Trapani, G ;

Biggio, G .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (21) :4655-4668

[2] EQUILIBRIUM ACIDITIES IN DIMETHYL-SULFOXIDE SOLUTION [J].

BORDWELL, FG .

ACCOUNTS OF CHEMICAL RESEARCH, 1988, 21 (12) :456-463

[3] Development of two synthetic routes to CE-178,253, a CB1 antagonist for the treatment of obesity [J].

Brandt, Thomas A. ;

Caron, Stephane ;

Damon, David B. ;

DiBrino, Joseph ;

Ghosh, Arun ;

Griffith, David A. ;

Kedia, Sandeep ;

Ragan, John A. ;

Rose, Peter R. ;

Vanderplas, Brian C. ;

Wei, Lulin .

TETRAHEDRON, 2009, 65 (16) :3292-3304

[4]

Coles MP, 2006, DALTON T, P985, DOI 10.1039/b515490a

[5] ELECTROCHEMICAL-BEHAVIOR OF AMIDINE HYDROCHLORIDES AND AMIDINES [J].

DAOUST, B ;

LESSARD, J .

CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE, 1995, 73 (03) :362-374

[6] Carbon Dioxide Induced Phase Switching for Homogeneous-Catalyst Recycling [J].

Desset, Simon. L. ;

Cole-Hamilton, David J. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2009, 48 (08) :1472-1474

[7]

Dunn P.J., 2005, Compreh. Org. Funct. Group Transform. II, V5, P655

[8] Application of fragment-based lead generation to the discovery of novel, cyclic amidine β-secretase inhibitors with nanomolar potency, cellular activity, and high ligand efficiency [J].

Edwards, Philip D. ;

Albert, Jeffrey S. ;

Sylvester, Mark ;

Aharony, David ;

Andisik, Donald ;

Callaghan, Owen ;

Campbell, James B. ;

Carr, Robin A. ;

Chessari, Gianni ;

Congreve, Miles ;

Frederickson, Martyn ;

Folmer, Rutger H. A. ;

Geschwindner, Stefan ;

Koether, Gerard ;

Kolmodin, Karin ;

Krumrine, Jennifer ;

Mauger, Russell C. ;

Murray, Christopher W. ;

Olsson, Lise-Lotte ;

Patel, Sahil ;

Spear, Nate ;

Tian, Gaochao .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (24) :5912-5925

[9] Synthesis and evaluation of new difluoromethyl azoles as antileishmanial agents [J].

Ferreira, Sabrina B. ;

Costa, Marilia S. ;

Boechat, Nubia ;

Bezerra, Romulo J. S. ;

Genestra, Marcelo S. ;

Canto-Cavalheiro, Marilene M. ;

Kover, Warner B. ;

Ferreira, Vitor F. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2007, 42 (11-12) :1388-1395

[10]

GILBERT HF, 1979, J AM CHEM SOC, V101, P5774, DOI 10.1021/ja00513a051

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