General and Rapid Pyrimidine Condensation by Addressing the Rate Limiting Aromatization

被引：27

作者：

Fandrick, Daniel R. ^{[1
]}

Reinhardt, Delia ^{[1
]}

Desrosiers, Jean-Nicolas ^{[1
]}

Sanyal, Sanjit ^{[1
]}

Fandrick, Keith R. ^{[1
]}

Ma, Shengli ^{[1
]}

Grinberg, Nelu ^{[1
]}

Lee, Heewon ^{[1
]}

Song, Jinhua J. ^{[1
]}

Senanayake, Chris H. ^{[1
]}

机构：

[1] Boehringer Ingelheim Pharmaceut Inc, Chem Dev, Ridgefield, CT 06877 USA

来源：

ORGANIC LETTERS | 2014年 / 16卷 / 11期

关键词：

MICROWAVE-ASSISTED SYNTHESIS; SOLVATION; ACIDITIES; PYRIDINES; AMIDINES; ACCESS; WATER;

D O I：

10.1021/ol500886a

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The rate limiting aromatization within the condensation approach toward pyrimidines utilizing amidines and activated olefins was addressed to provide for a general and rapid process. A strong solvent effect was elucidated to affect the rate for the initial alkoxide elimination from the intermediate Michael adduct wherein polar aprotic solvents demonstrate an addition controlled aromatization. Spectroscopic studies support a solvent dependent equilibrium between the amidine and alkoxide base wherein the rate for aromatization is optimal when the equilibrium toward the amidine anion was strongly favored.

引用

页码：2834 / 2837

页数：4

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