Straightforward Synthesis of Functionalized Furo[3,4-d] pyrimidine-2,4-diones

被引:6
作者
De Coen, Laurens M. [1 ]
Jatczak, Martyna [1 ]
Muylaert, Koen [1 ]
Mangelinckx, Sven [1 ]
Stevens, Christian V. [1 ]
机构
[1] Univ Ghent, Dept Sustainable Organ Chem & Technol, Fac Biosci Engn, B-9000 Ghent, Belgium
来源
SYNTHESIS-STUTTGART | 2015年 / 47卷 / 09期
关键词
heterocycles; ring closure; alkylation; rearrangement; hydrogenation; MTOR INHIBITORS; CANCER-THERAPY;
D O I
10.1055/s-0034-1380321
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
An efficient synthesis of furo[3,4-d]pyrimidine-2,4-diones has been accomplished via a straightforward three-step pathway. Curtius rearrangement of 4-(methoxycarbonyl)furan-3-carboxylic acid and subsequent reaction with a variety of amines resulted in the corresponding intermediate ureids, which could be ring closed to the bicyclic scaffold in good yields. Functionalization of N-1 afforded a small library of new heterocycles. (Partial) hydrogenation of the furo[3,4-d]pyrimidine- 2,4-diones led to the 5,7-dihydro- and tetrahydrofuro[3,4-d]pyrimidine- 2,4-diones.
引用
收藏
页码:1227 / 1237
页数:11
相关论文
共 17 条
[1]  
Bergeron P., 2010, CHEM ABSTR, V154
[2]  
Bergeron P., 2010, PCT Int. Appl, Patent No. 2010151601
[3]  
Chuanlang Z., 2008, Patent, Patent No. [CN101293909, 101293909]
[4]  
Chuanlang Z., 2008, CHEM ABSTR, V149
[5]   Potent, Selective, and Orally Bioavailable Inhibitors of Mammalian Target of Rapamycin (mTOR) Kinase Based on a Quaternary Substituted Dihydrofuropyrimidine [J].
Cohen, Frederick ;
Bergeron, Philippe ;
Blackwood, Elizabeth ;
Bowman, Krista K. ;
Chen, Huifen ;
DiPasquale, Antonio G. ;
Epler, Jennifer A. ;
Koehler, Michael F. T. ;
Lau, Kevin ;
Lewis, Cristina ;
Liu, Lichuan ;
Ly, Cuong Q. ;
Malek, Shiva ;
Nonomiya, Jim ;
Ortwine, Daniel F. ;
Pei, Zhonghua ;
Robarge, Kirk D. ;
Sideris, Steve ;
Trinh, Lan ;
Truong, Tom ;
Wu, Jiansheng ;
Zhao, Xianrui ;
Lyssikatos, Joseph P. .
JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (09) :3426-3435
[7]   Synthesis and evaluation of furo[3,4-d]pyrimidinones as selective α1a-adrenergic receptor antagonists [J].
Lagu, B ;
Tian, D ;
Chiu, G ;
Nagarathnam, D ;
Fang, J ;
Shen, QR ;
Forray, C ;
Ransom, RW ;
Chang, RSL ;
Vyas, KP ;
Zhang, KY ;
Gluchowski, C .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (02) :175-178
[8]  
Parlati F., 2014, Preparation of fused pyrimidines as inhibitors of p97 complex 1, Patent No. [WO2014015291, 2014015291]
[9]   Synthesis of Novel Thymine-β-lactam Hybrids and Evaluation of Their Antitumor Activity [J].
Piens, Nicola ;
De Vreese, Rob ;
De Neve, Nympha ;
Van Hecke, Kristof ;
Balzarini, Jan ;
De Kimpe, Norbert ;
D'hooghe, Matthias .
SYNTHESIS-STUTTGART, 2014, 46 (18) :2436-2444
[10]   The mTOR Signalling Pathway in Human Cancer [J].
Populo, Helena ;
Lopes, Jose Manuel ;
Soares, Paula .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2012, 13 (02) :1886-1918