synthesis of new riminophenazines with pyrimidine and pyrazine substitution at the 2-n position合成新的riminophenazines嘧啶和吡嗪替换2 n的位置.pdf

Molecules 2011, 16, 6985-6991; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis of New Riminophenazines with Pyrimidine and Pyrazine Substitution at the 2-N Position Gang Zhang, Hao Zhang, Xiaojian Wang, Chun Li, Haihong Huang and Dali Yin * Department of Medicinal Chemistry, Beijing Key Laboratory of Active Substance Discovery and Drugability Evaluation, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing 100050, China * Author to whom correspondence should be addressed; E-Mail: yindali@; Tel.: +86-10 Fax: +86-10 Received: 11 July 2011; in revised form: 6 August 2011 / Accepted: 9 August 2011 / Published: 16 August 2011 Abstract: New riminophenazines with pyrimidine and pyrazine substituents at the 2-position were successfully synthesized. The key step is the 2-N-arylation of riminophenazines with pyrimidine and pyrazine. The optimized reaction conditions involve the use of a Pd (dba) /DPPF/Cs CO /toluene combination. 2 3 2 3 Keywords: riminophenazine; N-arylation; palladium catalyst 1. Introduction Riminophenazines such as clofazimine (Figure 1) are of great interest to many medicinal chemists due to their various biological activities in the anti-mycobacterial [1,2], anti-tumor [3] and anti-inflammatory areas [4-6], especially for multidrug resistant tuberculosis (M