A facile synthesis of pyrazoles with multi-point structural diversity by 1,3-dipolar cycloaddition

被引：22

作者：

Cheung, Kwai Ming J. ^{[1
]}

Reynisson, Johannes ^{[1
]}

McDonald, Edward ^{[1
]}

机构：

[1] Inst Canc Res, Canc Res UK Canc Therapeut Unit, Sutton SM2 5NG, Surrey, England

来源：

TETRAHEDRON LETTERS | 2010年 / 51卷 / 45期

关键词：

Pyrazole; 1,3-Dipolar cycloaddition; HOMO-LUMO; ANTI-DIABETIC ACTIVITY; IN-VITRO; DERIVATIVES; ANTITUMOR; ALKYNES; DESIGN; POTENT;

D O I：

10.1016/j.tetlet.2010.09.012

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

We describe the synthesis of diverse pyrazoles by 1,3-dipolar cycloaddition of ethyl diazoacetate with various acetylenes in refluxing toluene. The product pyrazoles are useful starting points for preparing a diverse collection of trisubstituted pyrazole carboxamides. For aryl and heteroaryl alkynes a single product is obtained while alkyl alkynes afford a ca. 6:1 mixture of regioisomers. The observed regioselectivity for the cycloaddition step and the ease of reaction are consistent with predictions derived from computing the HOMO-LUMO energies of the reactants. (C) 2010 Published by Elsevier Ltd.

引用

页码：5915 / 5918

页数：4

共 32 条

[1]

Abadi AH, 2003, CHEM PHARM BULL, V51, P838

[2]

AKHREM AA, 1975, ZH OBSHCH KHIM+, V45, P1401

[3] Cinnamoyl nitrogen mustard derivatives of pyrazole analogues of tallimustine modified at the amidino moiety: design, synthesis, molecular modeling and antitumor activity studies [J].

Baraldi, PG ;

Beria, I ;

Cozzi, P ;

Geroni, C ;

Espinosa, A ;

Gallo, MA ;

Entrena, A ;

Bingham, JP ;

Hartley, JA ;

Romagnoli, R .

BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (14) :3911-3921

[4] The effect of 1,3-diaryl-[1H]-pyrazole-4-acetamides on glucose utilization in ob/ob mice [J].

Bebernitz, GR ;

Argentieri, G ;

Battle, B ;

Brennan, C ;

Balkan, B ;

Burkey, BF ;

Eckhardt, M ;

Gao, JP ;

Kapa, P ;

Strohschein, RJ ;

Schuster, HF ;

Wilson, M ;

Xu, DD .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (16) :2601-2611

[5] Design, synthesis and biological evaluation of some pyrazole derivatives as anti-inflammatory-antimicrobial agents [J].

Bekhit, AA ;

Abdel-Aziem, T .

BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (08) :1935-1945

[6] The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors [J].

Cheung, KMJ ;

Matthews, TP ;

James, K ;

Rowlands, MG ;

Boxall, KJ ;

Sharp, SY ;

Maloney, A ;

Roe, SM ;

Prodromou, C ;

Pearl, LH ;

Aherne, GW ;

McDonald, E ;

Workman, P .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (14) :3338-3343

[7] Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design [J].

Dymock, BW ;

Barril, X ;

Brough, PA ;

Cansfield, JE ;

Massey, A ;

McDonald, E ;

Hubbard, RE ;

Surgenor, A ;

Roughley, SD ;

Webb, P ;

Workman, P ;

Wright, L ;

Drysdale, MJ .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (13) :4212-4215

[8]

Farghaly AM, 2001, PHARMAZIE, V56, P28

[9]

*FIJ LTD, 2000, CACHE 6 1

[10]

Fleming I., 2007, Frontier orbitals and organic chemical reactions, P1

← 1 2 3 4 →