Automated process research and the optimization of the synthesis of 4(5)-(3-pyridyl)imidazole

被引：13

作者：

Kirchhoff, EW ^{[1
]}

Anderson, DR ^{[1
]}

Zhang, SL ^{[1
]}

Cassidy, CS ^{[1
]}

Flavin, MT ^{[1
]}

机构：

[1] Medichem Res Inc, Lemont, IL 60439 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2001年 / 5卷 / 01期

关键词：

D O I：

10.1021/op0000881

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Automated process development technology was applied to the synthesis of 4(4)-(3-pyridyl)imidazole. This method utilizes automated liquid handling equipment coupled with statistically designed protocols for rapid process optimization. Two experimental sets were carried out based on a three-level factorial and central composite designs to optimise the product yield, The central composite design was repeated on one-fifth the scale to test the capabilities of the automated equipment. The reaction variables investigated were temperature and stoichiometry of formamide. The optimum in situ yield of 4(5)-(3-pyridyl)-imidazole was found to be at 160 degreesC and 9 equiv of formamide, The results from the automated technology can be applied to larger-scale synthesis of the desired compound.

引用

页码：50 / 53

页数：4

共 14 条

[1]

AIKENS J, 1999, CHEM BOND NOV

[2] SYNTHESES BY MEANS OF ACID AMIDES, PARTICULARLY BY MEANS OF FORMAMIDE [J].

BREDERECK, H ;

GOMPPER, R ;

VONSCHUH, HG ;

THEILIG, G .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 1959, 71 (24) :753-774

[3]

BREDERECK H, 1964, NEWER METHODS PREP, V3, P241

[4]

CONDEIU C, 1999, UNPUB

[5] A practical approach to accelerated process screening and optimisation [J].

Emiabata-Smith, DF ;

Crookes, DL ;

Owen, MR .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 1999, 3 (04) :281-288

[6] DESIGN OF POTENT NON-THIOUREA H-3 RECEPTOR HISTAMINE-ANTAGONISTS [J].

GANELLIN, CR ;

HOSSEINI, SK ;

KHALAF, YS ;

TERTIUK, W ;

ARRANG, JM ;

GARBARG, M ;

LIGNEAU, X ;

SCHWARTZ, JC .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (17) :3342-3350

[7]

Grimmett M., 1970, Adv. Heterocycl. Chem, V12, P103, DOI [10.1016/S0065-2725(08)60973-3, DOI 10.1016/S0065-2725(08)60973-3]

[8]

Grimmett M.R., 1997, IMIDAZOLE BENZIMIDAZ

[9]

HARRING S, 2000, COMMUNICATION

[10]

LINDSEY JS, 1997, COMBINATORIAL CHEM

← 1 2 →