3
On the other hand, 2-amino-1H-indole-3-carbonitrile
and 3-amino-1H-indole-2-carbonitrile did not produce the
desired products 10 (Scheme 1). Based on the assumption
7
9
Table 3. Synthesis of various five-membered ring fused
pyrimidine-2,4(1H,3H)-diones.a
8
,
that the N-H on the indole ring prevented the reaction, N-
substituted 3-amino-1H-indole-2-carbonitrile 11 was
reaction with CO2; although the reaction proceeded, the
deacylated compound 10 was unexpectedly formed in 88%
yield.
O
CN
[HDBN+][TFE-]
X
X
Z
NH
+
CO2
Y
Y
NH
2
Z
N
H
O
5
6
O
CN
[HDBN+][TFE– ] (6.0 eq.)
Entry
Substrate
T
[°C]
Time
[h]
Product
Isolated
yield 6
[%]
NH
NH2
CO2 (balloon), 90 °C, 18 h
N
N
N
O
H
H
H
7
8
O
CN
NH
H
NH2
CN
[HDBN+][TFE– ] (6.0 eq.)
CO2 (balloon), 90 °C, 18 h
5a
5b
N
O
6a
NH
NH
1
2
3
4
5
6
7
90
48
48
48
24
20
72
18
94
88
86
75
70
65
92
S
S
NH
2
N
S
N
O
O
N
H
H
O
H
O
9
10
CN
NH
NH2
H
N
6b
[HDBN+][TFE– ] (6.0 eq.)
CO2 (balloon), 90 °C, 18 h
90
90
90
60
90
90
O
2
S
N
CN
NH
H
N
N
H
O
O
11
O
CN
NH
5c
10 ( 88%)
6c
NH
S
S
N
O
Scheme 1. Synthesis of indolopyrimidine-2,4-diones.
2
H
O
Conclusion
N
CN
NH
N
NH
5d
S
6d
2
In summary, we have developed a new and efficient system
for the preparation of various heterocycle-fused pyrimidine-
2,4(1H,3H)-diones under atmospheric pressure via the reaction of
CO2 with the corresponding heterocyclic substrates in the
presence of [HDBN+][TFE–] which acts as a dual solvent and
reaction promoter.
S
O
N
H
O
CN
S
5e
NH
S
6e
NH2
CN
MeOOC
N
H
O
MeOOC
O
N
5f
Acknowledgment
NH
N
N
NH
2
6f
N
N
H
O
We are grateful to the National Natural Science Foundation of
China (21562010, 21601039), the Doctoral Program Foundation
of Guizhou Medical University (J[2015]015 to L.Z.), the
Foundation of Office of Science & Technology of Guizhou
(LH[2016]7359 to L.Z.) for financial support
O
CN
NH
NH
5g
O
6g
O
2
O
N
H
a
Reagents and conditions: substrate
5 (1 mmol), ionic liquid (6
mmol), CO2 (balloon).
Mizuno. T, Mihara M, Nakai T, Iwai T, Ito T. Synthesis. 2007, 2524-
2528.
References and notes
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1171-1188.
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3.
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19. General
experimental
procedure
procedure:
2-Amino-
nicotinonitrile 1 (1.0 mmol), and [HDBN+][TFE–] (6.0 mmol) were
loaded into a 10 mL glass reaction tube equipped with a magnetic
stirrer. The air in the reactor was replaced by CO2. Then, the reactor
was stirred at 60 °C for 3 h under CO2 using a balloon. Upon reaction
completion, the reaction was cooled to room temperature and quenched
with a saturated ammonium chloride solution. The mixture was filtered
to afford the crude product, which was purified by chromatography
(silica gel, methanol/dichloromethane=1/20) to give compound 2 as a
white solid (95%). 1H NMR (400 MHz, DMSO-d6): δ = 11.70 (s, 1H),
11.51 (s, 1H), 8.60 (d, J = 2.4 Hz, 1H), 8.26 (d, J = 4.0 Hz, 1H), 7.25
6.
7.
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