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Synlett 2010(1): 101-106  
DOI: 10.1055/s-0029-1218530
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Efficient Copper-Catalyzed Synthesis of 4-Aminoquinazoline and 2,4-Diaminoquinazoline Derivatives

Xiaobo Yanga,b, Hongxia Liuc, Hua Fu*a, Renzhong Qiao*b, Yuyang Jiangc, Yufen Zhaoa
a Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China
Fax: +86(10)62781695; e-Mail: fuhua@mail.tsinghua.edu.cn;
b State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P. R. of China
e-Mail: qiaorz@mail.buct.edu.cn;
c Key Laboratory of Chemical Biology, Guangdong Province, College of Shenzhen, Tsinghua University, Shenzhen 518057, P. R. of China
Further Information

Publication History

Received 21 September 2009
Publication Date:
01 December 2009 (online)

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Abstract

We have developed an efficient copper-catalyzed method for the synthesis of 4-aminoquinazoline and 2,4-diaminoquinazoline derivatives via reactions of substituted 2-bromo-benzonitriles with amidines or guanidine, and the method is of economical and practical advantage.

Key words

copper - Ullmann-type reaction - cross-coupling - quinazoline - synthetic method

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27

General Procedure for the Synthesis of Compounds 3a-m A 25 mL round-bottom flask was charged with a magnetic stirrer and DMF (3 mL), substituted 2-bromobenzonitrile (1, 1 mmol), amidine hydrochloride (2, 1.2 mmol), DMEDA (0.2 mmol, 18 mg), and K2CO3 (2 mmol, 138 mg) [2 mmol (656 mg) of Cs2CO3 were used for acetamidine hydro-chloride] after stirring of the mixture for 15 min under nitrogen atmosphere, and CuI (0.1 mmol, 19 mg) was added to the flask. The mixture was stirred at 80 ˚C for the time indicated in Table  [²] . The resulting mixture was cooled to r.t. and filtered. The solid was washed with DMF (2 × 3 mL), and the combined filtrate was concentrated by the rotary evaporator, and the residue was purified by column chromatography on silica gel using CHCl3-MeOH (40:1 to 5:1) as eluent to give the desired product.
Cyclopropyl-4-aminoquinazoline (3c)
Eluent CHCl3-MeOH (40:1). Yield 134 mg (72%). White solid; mp 198-200 ˚C. ¹H NMR (300 MHz, DMSO-d 6): δ = 8.12 (d, 1 H, J = 7.9 Hz), 7.58 (m, 4 H), 7.34 (t, 1 H, J = 7.4 Hz), 1.99 (m, 1 H, J = 7.5 Hz), 1.05-0.87 (m, 4 H). ¹³C NMR (75 MHz, DMSO-d 6): δ = 167.6, 162.3, 150.5, 133.2, 126.9, 124.5, 124.0, 113.4, 18.4, 9.4. HRMS: m/z calcd for C11H11N3 [M + H]+: 186.1031; found: 186.1037.