Abstract
A regioselective, mild, convenient, and effective condition is
developed for the inclusion of glyoxylic acid as formaldehyde equivalent
in the 3CC reaction towards synthesis of 3-aminoalkyl imidazo-azines.
In general, formaldehydes do not perform well with Ugi-type multicomponent
sequences, and the method reported here is a regioselective and
high-yielding one for the HCHO variant of Groebke-Blackburn-Bienaymé reaction.
Key words
Groebke-Blackburn-Bienaymé - multicomponent reaction - aminoimidazoazines - formaldehyde - glyoxylic
acid
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10
Representative
Procedure for the Synthesis of
N
-(2,6-dimethylphenyl)imidazo[1,2-
a
]pyridin-3-amine
(3b, Table 2)
1b , 1.05 mmol) in MeOH (1.5 mL), was added
glyoxylic acid (1.78 mmol) followed by HClO4 (0.105 mmol),
and the solution was stirred for 10 min. 2-Isocyano-1,3-dimethylbenzene
(1.05 mmol) was added to this mixture, and the solution was stirred
for 12 h. MeOH was evaporated from the reaction mixture, and the crude
was purified through silica gel chromatography to provide 3b in 77% yield. ¹ H
NMR (400 MHz, DMSO-d
6 ): J = 8
Hz, 1 H), 7.81 (d, J = 4
Hz, 2 H), 7.60 (s, 1 H), 7.52-7.48 (m, 1 H), 7.11 (d, J = 8 Hz,
2 H), 7.05-7.02 (m, 3 H), 2.09 (s, 6 H). ¹³ C
NMR (400 MHz, DMSO-d
6 ): m/z calcd
for C15 H16 N3 : 238.13387; found:
238.13377. LC-MS (ES): 98.6% (λ = 214
nm).
11 Formation of regioisomer was observed
during optimization studies using paraformaldehyde as formaldehyde
source (entry 8, Table
[¹
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13 Nichol, G. S.; Sharma, A.; Li, H.
Y. unpublished results .
