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dissolved in anhydrous acetonitrile (8 mL), and NaH (95 %;
.7 equiv.) was added portionwise while stirring the mixture under
an inert gas. After 2 h, 4-oxocyclopent-2-en-1-yl acetate [(±)-10]
was dried with Na SO , and the solvent was evaporated. The resi-
due was submitted to chromatographic separation to isolate the
2
4
1
products. Adduct 15 was found to be identical to the product de-
[
10]
(1 g, 7.14 mmol) was dissolved in the minimum amount of anhy- scribed in the literature,
while its regioisomer 16 was fully char-
drous acetonitrile, and the resulting solution was added dropwise
to the reaction mixture under vigorous stirring at 0 °C. The tempera-
ture was allowed to rise to ambient temperature over the reaction
time of 3.5 h after the reagent addition. The reaction was then
quenched with ice, and CH Cl was added. The organic phase was
acterized.
Compound 16: Yield 0.27 g (16 %). M.p. 210–215 °C (diisopropyl
–
1 1
ether/ethanol). IR: ν˜ = 1753 (C=O) cm . H NMR (400 MHz, CDCl ,
3
25 °C): δ = 2.72 and 3.40 (m, 2 H + 2 H, CH CH ), 7.28 (s, 1 H, CH=
2
2
13
2
2
), 8.43 (s, 1 H, N=CH), 8.91 (s, 1 H, N=CH) ppm. C NMR (100 MHz,
dried with Na SO , and the solvent was evaporated. The residue
2
4
CDCl , 25 °C): δ = 27.7, 33.4, 119.6, 132.8, 138.3, 141.3, 151.3, 152.3,
3
was submitted to chromatographic separation to isolate the pro-
ducts. Regioisomers 12a,b and 13a,b were obtained and fully char-
acterized.
153.3, 156.8, 161.2, 204.8 ppm. C H ClN O (234.64): calcd. C 51.19,
10 7 4
H 3.01, N 23.88; found C 51.13, H 3.02, N 23.85.
Synthesis of 6-Chloropurine Derivatives 15 and 16 in the Pres-
ence of DBU (HPLC Analyses): 6-Chloropurine (14) (50 mg,
Compound 12a: Yield 1.59 g (75 %). M.p. 170–172 °C (diisopropyl
–
1 1
ether/ethanol). IR: ν˜ = 1755, 1729 (C=O) cm . H NMR (400 MHz,
1
equiv.) was dissolved in anhydrous acetonitrile (6 mL), and DBU
[
D ]DMSO, 25 °C): δ = 2.55 and 2.83 (dd, J = 19, 7 Hz, 2 H, CH ),
6
2
(1 equiv.) was added portionwise while stirring under an inert gas.
5
6
.69 (m, 1 H, CH–N), 5.86 (d, J = 8 Hz, 1 H, =CH–CO), 6.49 (dd, J =
, 2 Hz, 1 H, CH=), 7.62 (m, 3 H, arom.), 7.68 (d, J = 8 Hz, 1 H, CH=
After 2 h, 4-oxocyclopent-2-en-1-yl acetate [(±)-10] (1 equiv.) was
dissolved in the minimum amount of anhydrous acetonitrile, and
the resulting solution was added dropwise to the reaction mixture
under vigorous stirring at 0 °C or at –20 °C. Samples of the reaction
mixtures (1 mL) were taken after 30–384 min, quickly quenched
with ice, and analysed by HPLC. Quantitative determinations were
done in duplicate.
)
, 7.82 (d, J = 6, 3 Hz, 1 H, =CH), 8.02 (d, J = 8 Hz, 2 H, arom.) ppm.
1
3
C NMR (100 MHz, [D ]DMSO, 25 °C): δ = 59.2, 103.8, 131.8, 132.8,
6
1
33.5, 137.9, 139.4, 146.3, 151.8, 162.7, 164.3, 171.9, 207.8 ppm.
C H N O (296.28): calcd. C 64.86, H 4.08, N 9.46; found C 64.86,
16 12 2 4
H 4.10, N 9.42.
Compound 12b: Yield 1.88 g (85 %). M.p. 179–182 °C (diisopropyl
Synthesis of Adenine Derivatives 19 and 20: An excess of ade-
nines 18a–18f (1.5 equiv.) was dissolved in anhydrous acetonitrile
(8 mL), and NaH (95 %; 1.7 equiv.) was added portionwise while
stirring under an inert gas. After 2 h, 4-oxocyclopent-2-en-1-yl ace-
tate [(±)-10] (1 g, 7.14 mmol) was dissolved in the minimum amount
of anhydrous acetonitrile, and the resulting solution was added
dropwise to the reaction mixture under vigorous stirring at 0 °C.
The temperature was allowed to rise to ambient temperature over
the reaction time of 3.5 h after the reagent addition. The reaction
was quenched with ice, and CH Cl was added. The organic phase
–
1 1
ether/ethanol). IR: ν˜ = 1755, 1747 (C=O) cm . H NMR (400 MHz,
[
(
D ]DMSO, 25 °C): δ = 1.83 (d, J = 7 Hz, 3 H, CH ), 2.53 and 2.84
6 3
dd, J = 16, 2 Hz, 2 H, CH ), 5.71 (m, 1 H, CH–N), 6.49 (dd, J = 6,
2
2
Hz, 1 H, CH=), 6.55 (s, 1 H, =CH–CO), 7.61 (m, 3 H, arom.), 7.94 (d,
J = 8 Hz, 1 H, CH=), 7.79 (m, 2 H, arom.), 8.08 (d, J = 7 Hz, 1 H, CH=
)
ppm. 13C NMR (100 MHz, [D ]DMSO, 25 °C): δ = 11.8, 56.0, 109.6,
6
1
1
29.5, 130.2, 130.4, 131.2, 135.5, 137.2, 139.1, 149.3, 160.6, 162.6,
67.2, 169.7, 205.5 ppm. C H N O (310.30): calcd. C 65.80, H 4.55,
1
7 14 2 4
N 9.03; found C 65.85, H 4.51, N 9.02.
2
2
was dried with Na SO , and the solvent was evaporated. The resi-
Compound 13a: Yield 0.19 g (9 %). M.p. 174–177 °C (diisopropyl
2
4
–
1
1
dues were submitted to chromatographic separation to isolate the
products. Regioisomers 19a–19f and 20b, 20d–20f were obtained
and fully characterized.
ether/ethanol). IR: ν˜ = 1744, 1724 (C=O) cm . H NMR (300 MHz,
[
(
7
D ]DMSO, 25 °C): δ = 2.45 and 3.10 (m, 2 H + 2 H, CH CH ), 6.11
6 2 2
d, J = 8 Hz, 1 H, =CH–CO), 6.57 (s, 1 H, CH=), 7.62 (m, 2 H, arom.),
.82 (t, J = 8 Hz, 1 H, arom.), 8.09 (d, J = 8 Hz, 2 H, arom.), 8.18 (d,
Compound 19a: Yield 0.65 g (42 %). M.p. 202–206 °C (diisopropyl
1
3
J = 8 Hz, 1 H, CH=) ppm. C NMR (75 MHz, [D ]DMSO, 25 °C): δ =
–1 1
6
ether/ethanol). IR: ν = 3250, 3320 (NH ), 1686 (C=O) cm . H NMR
˜
2
2
1
8.8, 33.3, 103.2, 119.8, 129.5, 130.6, 130.8, 135.8, 142.0, 147.9, 161.1,
66.9, 168.9, 206.3 ppm. C H N O (296.28): calcd. C 64.86, H 4.08,
(
400 MHz, [D ]DMSO, 25 °C): δ = 2.72 and 2.99 (dd, J = 18, 7, 3 Hz,
6
1
6
12
2
4
1 H + 1 H, CH ), 5.91 (m, 1 H, CH–N), 6.51 (dd, J = 6, 2 Hz, 1 H, =
2
N 9.46; found C 64.84, H 4.11, N 9.44.
CH–CO), 7.25 (s, 2 H, NH ), 7.86 (dd, J = 6, 2 Hz, 1 H, CH=), 8.12 (s,
2
13
1
H, N=CH), 8.16 (s, 1 H, N=CH) ppm. C NMR (100 MHz, [D ]DMSO,
6
Compound 13b: Yield 0.16 g (7 %). M.p. 164–167 °C (diisopropyl
–
1
1
25 °C): δ = 41.1, 54.0, 116.1, 119.0, 136.0, 138.6, 139.5, 149.2, 152.4,
ether/ethanol). IR: ν˜ = 1747, 1723 (C=O) cm . H NMR (300 MHz,
1
53.9, 156.0, 160.8, 205.6 ppm. C H N O (215.21): calcd. C 55.81, H
10 9 5
[
D ]DMSO, 25 °C): δ = 1.95 (s, 3 H, CH ), 2.45 and 3.10 (m, 2 H + 2
6
3
4.22, N 32.54; found C 55.83, H 4.22, N 32.55.
H, CH CH ), 6.55 (s, 1 H, CH=), 7.61 (m, 2 H, arom.), 7.81 (t, J = 8 Hz,
2
2
1
H, arom.), 8.06 (d, J = 8 Hz, 1 H, CH=), 8.07 (d, J = 8 Hz, 2 H, arom.) Compound 19b: Yield 0.82 g (47 %). M.p. 178–179 °C (diisopropyl
13
–1
1
ppm. C NMR (75 MHz, [D ]DMSO, 25 °C): δ = 11.9, 29.0, 33.3, 111.4,
1
2
ether/ethanol). IR: ν = 3288 (NH), 1718 (C=O) cm . H NMR
6
˜
19.3, 129.5, 130.6, 130.8, 135.7, 137.3, 147.9, 161.9, 167.2, 168.9, (400 MHz, [D ]DMSO, 25 °C): δ = 1.17 (t, J = 7 Hz, 3 H, CH ), 2.72
6
3
06.3 ppm. C H N O (310.30): calcd. C 65.80, H 4.55, N 9.03;
and 2.99 (dd, J = 18, 7, 3 Hz, 1 H + 1 H, CH ), 3.51 (br. s, 2 H, CH N),
2 2
17
14
2
4
found C 65.83, H 4.52, N 9.05.
5.92 (m, 1 H, CH–N), 6.51 (dd, J = 6, 2 Hz, 1 H, =CH–CO), 7.78 (br. s,
H, NH), 7.86 (dd, J = 6, 2 Hz, 1 H, CH=), 8.15 (s, 1 H, N=CH), 8.18
s, 1 H, N=CH) ppm. 13C NMR (100 MHz, [D ]DMSO, 25 °C): δ = 15.1,
1
(
Synthesis of 6-Chloropurine Derivatives 15 and 16: An excess of
6
6-chloropurine (14) (1.5 equiv.) was dissolved in anhydrous acetoni-
4
2
1.5, 54.4, 114.1, 118.0, 136.4, 139.6, 144.0, 152.8, 154.8, 158.8, 161.2,
06.1 ppm. C H N O (243.26): calcd. C 59.25, H 5.39, N 28.79;
trile (8 mL), and NaH (95 %; 1.7 equiv.) was added portionwise while
stirring under an inert gas. After 2 h, 4-oxocyclopent-2-en-1-yl ace-
tate [(±)-10] (1 g, 7.14 mmol) was dissolved in the minimum amount
12 13 5
found C 59.23, H 5.32, N 28.75.
of anhydrous acetonitrile, and the resulting solution was added Compound 20b: Yield 0.02 g (1 %). M.p. >240 °C (dec.) (diisopropyl
–
1
1
dropwise to the reaction mixture under vigorous stirring at 0 °C.
The temperature was allowed to rise to ambient temperature over
the reaction time of 3.5 h after the reagent addition. The reaction
was quenched with ice, and CH Cl was added. The organic phase
ether/ethanol). IR: ν˜ = 3280 (NH), 1698 (C=O) cm . H NMR
(400 MHz, [D ]DMSO, 25 °C): δ = 1.06 (t, J = 7 Hz, 3 H, CH ), 1.77
and 1.89 (m, 2 H + 2 H, CH CH ), 4.18 (br. s, 2 H, CH N), 6.97 (s, 1
H, =CH), 7.90 (d, J = 7 Hz, 1 H, NH), 8.35 (s, 1 H, N=CH), 8.65 (s, 1
6
3
2
2
2
2
2
Eur. J. Org. Chem. 2016, 983–991
www.eurjoc.org
989
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim