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 K2 CO3 (2 mmol,
138 mg) [2 mmol (656 mg) of Cs2 CO3 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 3 -MeOH (40:1 to 5:1) as eluent to
give the desired product.Cyclopropyl-4-aminoquinazoline
(3c)
3 -MeOH (40:1).
Yield 134 mg (72%). White solid; mp 198-200 ˚C. ¹ H
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). ¹³ C
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 C11 H11 N3 [M + H]+ :
186.1031; found: 186.1037.
