Stille coupling reactions in the synthesis of hypoxia-selective 3-alkyl-1,2,4-benzotriazine 1,4-dioxide anticancer agents.
J Org Chem
; 71(17): 6530-5, 2006 Aug 18.
Article
em En
| MEDLINE
| ID: mdl-16901140
ABSTRACT
The introduction of a 3-alkyl substituent is a key step in the synthesis of 1,2,4-benzotriazine 1,4-dioxide hypoxia-selective anticancer agents, such as SN29751. The Stille reaction of 3-chloro-1,2,4-benzotriazine 1-oxides (BTOs) 5 was inhibited by the presence of electron donating substituents on the benzo ring, thus limiting the range of compounds available for SAR studies. The use of 3-iodo-BTOs 8 did not provide a significant improvement in the yields of 3-ethyl-BTOs 6. Microwave-assisted Stille coupling of chlorides 5 gave dramatically improved yields, which were consistently superior to those from the corresponding iodides 8. The application of microwave-assisted synthesis extended the range of substituted BTOs available for SAR studies and provided an efficient, scalable synthesis of the investigational anticancer agent, SN29751 (1).
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxigênio
/
Triazinas
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Óxidos Heterocíclicos
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Antineoplásicos
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Nova Zelândia
País de publicação:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA