Flexible Synthesis of Pyrimidines with Chiral Monofluorinated and Difluoromethyl Side Chains

被引：70

作者：

Bannwarth, Pierre ^{[1
]}

Valleix, Alain ^{[2
]}

Gree, Danielle ^{[1
]}

Gree, Rene ^{[1
]}

机构：

[1] Univ Rennes 1, CNRS, UMR 6510, Lab Chim & Photon Mol, F-35042 Rennes, France

[2] Ctr Etud Nucl Saclay, F-91191 Gif Sur Yvette, France

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2009年 / 74卷 / 12期

关键词：

ENANTIOSELECTIVE SYNTHESIS; MEDICINAL CHEMISTRY; BENZYLIC FLUORIDES; AGENTS; DERIVATIVES;

D O I：

10.1021/jo900674u

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Chiral pyrimidines with a fluorine atom in the benzylic position are easily accessible in high enantiomeric excesses from optically active propargylic intermediates by two complementary routes. Both the use of optically active propargylic fluorides and the fluorination of the chiral pyrimidine in the final stage give excellent results in terms of enantiocontrol. On the other hand, original pyrimidines with a difluoromethyl side chain are also obtained in a few steps from new propargylic ketones bearing a CHF2 substituent on the triple bond.

引用

页码：4646 / 4649

页数：4

共 27 条

[1] Recent advances (1995-2005) in fluorinated pharmaceuticals based on natural products [J].

Begue, Jean-Pierre ;

Bonnet-Delpon, Daniele .

JOURNAL OF FLUORINE CHEMISTRY, 2006, 127 (08) :992-1012

[2] New enantioselective synthesis of monofluorinated pyridines designed for the preparation of chemical libraries [J].

Blayo, Anne-Laure ;

Le Meur, Stephanie ;

Gree, Danielle ;

Gree, Rene .

ADVANCED SYNTHESIS & CATALYSIS, 2008, 350 (03) :471-476

[3] 4-(Isoxazol-3-yl)pyrimidines from Pyrimidinyl Nitrile Oxides [J].

Choung, Wonken ;

Lorsbach, Beth A. ;

Sparks, Thomas C. ;

Ruiz, James M. ;

Kurth, Mark J. .

SYNLETT, 2008, (19) :3036-3040

[4] Synthesis, tuberculosis inhibitory activity, and SAR study of N-substituted-phenyl-1,2,3-triazole derivatives [J].

Costa, Marilia S. ;

Boechat, Nubia ;

Rangel, Erica A. ;

Da Silva, Fernando de C. ;

de Souza, Alessandra M. T. ;

Rodrigues, Carlos R. ;

Castro, Helena C. ;

Junior, Ivan N. ;

Lourenco, Maria Cristina S. ;

Wardell, Solange M. S. V. ;

Ferreira, Vitor F. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (24) :8644-8653

[5]

EICHER T, 2003, CHEM HETEROCYCLES, pCH6

[6] 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

[7] ALKALI-METAL FLUORIDES AS EFFICIENT FLUORINATING AGENTS - ENANTIOCONTROLLED SYNTHESIS OF 2-FLUOROALKYL CARBOXYLATES AND 1-FLUOROALKYL BENZENES [J].

FRITZLANGHALS, E .

TETRAHEDRON-ASYMMETRY, 1994, 5 (06) :981-986

[8]

FRITZLANGHALS E, 1994, TETRAHEDRON LETT, V35, P1581

[9]

GORGUES A, 1974, B SOC CHIM FR II-CH, P529

[10] A new strategy for the synthesis of optically active benzylic fluorides and corresponding five-membered heteroaromatic analogues [J].

Gree, Danielle ;

Gree, Rene .

TETRAHEDRON LETTERS, 2007, 48 (31) :5435-5438

← 1 2 3 →