Synthesis of N,N-dimethyl(diethyl)-7-aryl-5-methyl-4,7-dihydrotetrazolo[1, 5-a]pyrimidine-6-carboxamides

Full text of DOI:10.1134/S1070428009060256

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 6, pp. 942–943. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © V.L. Gein, T.M. Zamaraeva, A.A. Zorina, E.B. Levandovskaya, N.V. Nosova, M.I. Vakhrin, 2009, published in Zhurnal
Organicheskoi Khimii, 2009, Vol. 45, No. 6, pp. 954–955.
SHORT
COMMUNICATIONS
Synthesis of N,N-Dimethyl(diethyl)-7-aryl-5-methyl-4,7-dihydro-
tetrazolo[1,5-a]pyrimidine-6-carboxamides
V. L. Gein, T. M. Zamaraeva, A. A. Zorina, E. B. Levandovskaya,
N. V. Nosova, and M. I. Vakhrin
Perm State Pharmaceutical Academy, ul. Lenina 48, Perm, 614990 Russia
e-mail: geinvl48@mail.ru
Received July 14, 2008
DOI: 10.1134/S1070428009060256
It is known that N,N-dimethyl-3-oxobutanamide
reacts with aromatic aldehydes in the presence of
piperidine to give N,N,N′,N′,6-pentamethyl-2-aryl-6-
hydroxy-4-oxocyclohexane-1,3-dicarboxamides [1].
Zhidovinova et al. [2] described three-component con-
densation of ethyl 3-oxobutanoate with aromatic alde-
hydes and 5-aminotetrazole, which led to the formation
of dihydrotetrazolopyrimidines [2].
While continuing studies in this line, we examined
for the first time three-component condensation of aro-
matic aldehydes with 5-aminotetrazole and such sub-
strates as N,N-dimethyl- and N,N-diethyl-3-oxobutan-
amides with a view to obtain new fused heterocyclic
systems. The reactions occurred at 120–150°C in 20–
60 min, and the products were the corresponding
N,N-dimethyl- and N,N-diethyl-7-aryl-5-methyl-4,7-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxamides
Ia, Ib, and IIa–IId. These compounds were isolated as
colorless crystalline substances which are soluble in
chloroform, DMF, and DMSO and insoluble in water.
1.90 ppm, the 7-H proton gave a singlet at δ 6.30–
6.65 ppm, and signal from the NH proton appeared as
δ 10.30–10.50 ppm; also signals from aromatic protons
were present. Signals from protons in the N-alkyl
group were located at δ 2.70 ppm (s, CH3; Ia, Ib) or at
δ 0.75-0.90 (m, CH3) and 3.05–3.10 ppm (m, CH2;
IIa–IId). Compound Ib displayed in the mass spec-
trum [M – CO]+ ion peak with m/z 301 and peaks
from fragment ions [M – CONMe2]+ (m/z 260), [M –
NMe2]+ (m/z 285), and [Ph]+ (m/z 77) in support of the
assumed structure.
N,N,5-Trimethyl-7-phenyl-4,7-dihydrotetrazolo-
[1,5-a]pyrimidine-6-carboxamide (Ia). A mixture of
0.01 mol of N,N-dimethyl-3-oxobutanamide, 0.01 mol
of benzaldehyde, and 0.01 mol of 1H-tetrazol-5-
amine was heated at 120–150°C for 20–60 min (until
gaseous products no longer evolved and the mixture
solidified). The melt was cooled and treated with etha-
nol, and the precipitate was filtered off and recrystal-
lized from ethanol. Yield 0.59 g (21%), mp 230–
232°C. IR spectrum, ν, cm–1: 1600 (C=C), 1675 (C=O),
The IR spectra of Ia, Ib, and IIa–IId contained
absorption bands due to stretching vibrations of the
amide carbonyl group (1660–1680 cm–1), NH group
(3150–3200 cm–1), and C=C bonds (1600–1620 cm–1).
In the 1H NMR spectra of Ia, Ib, and IIa–IId, protons
in the 5-methyl group resonated as a singlet at δ 1.80–
1
3200 (NH). H NMR spectrum, δ, ppm: 1.90 s (3H,
5-CH3), 2.70 s (6H, NCH3), 6.80 s (1H, 7-H), 8.14 m
(5H, C6H5), 10.50 s (1H, NH). Found, %: C 59.08,
59.21; H 5.62, 5.73; N 29.48, 29.62. C14H16N6O. Cal-
culated, %: C 59.14; H 5.67; N 29.56.
C6H4R'
CHO
CONR2
O
O
N
N
N
N
N
+
+
N
N
H2N
NR2
Me
N
N
Me
H
R'
H
Ia, Ib, IIa–IId
I, R = Me, R′ = H (a), 3-O2N (b); II, R = Et, R′ = H (a), 4-Cl (b), 3-F (c), 4-i-Pr (d).
942

SYNTHESIS OF N,N-DIMETHYL(DIETHYL)-7-ARYL-5-METHYL-4,7-DIHYDRO-...
943
Compounds Ib and IIa–IId were synthesized in
a similar way.
trum, ν, cm–1: 1600 (C=C), 1675 (C=O), 3200 (NH).
1H NMR spectrum, δ, ppm: 0.80 m (6H, CH3CH2),
1.80 s (3H, 5-CH3), 3.03 m (4H, NCH2), 6.37 s (1H,
7-H), 7.38 m (4H, C6H4), 10.35 s (1H, NH). Found, %:
C 58.07, 58.29; H 5.75, 5.91; N 25.33, 25.56.
C16H19FN6O. Calculated, %: C 58.17; H 5.80; N 25.44.
N,N,5-Trimethyl-7-(3-nitrophenyl)-4,7-dihydro-
tetrazolo[1,5-a]pyrimidine-6-carboxamide (Ib).
Yield 0.99 g (30%), mp 237–238°C. IR spectrum, ν,
1
cm–1: 1612 (C=C), 1680 (C=O), 3200 (NH). H NMR
spectrum, δ, ppm: 1.85 s (3H, 5-CH3), 2.70 s (6H,
NCH3), 6.64 s (1H, 7-H), 8.14 m (4H, C6H4), 10.57 s
(1H, NH). Found, %: C 50.98, 51.19; H 4.52, 4.67;
N 29.65, 29.85. C14H15N7O3. Calculated, %: C 51.06;
H 4.59; N 29.77.
N,N-Diethyl-7-(4-isopropylphenyl)-5-methyl-4,7-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxamide
(IId). Yield 1.21 g (34%), mp 217–219°C. IR spec-
trum, ν, cm–1: 1600 (C=C), 1680 (C=O), 3200 (NH).
1H NMR spectrum, δ, ppm: 0.90 m (6H, CH3CH2),
1.17 d [6H, (CH3)2CH], 1.85 s (3H, 5-CH3), 3.04 m
(4H, NCH2), 3.04 s [1H, (CH3)2CH], 6.45 s (1H, 7-H),
6.97 d and 7.08 d (2H each, C6H4, J = 7 Hz), 10.31 s
(1H, NH). Found, %: C 64.32, 64.45; H 7.28, 7.48;
N 23.63, 23.75. C19H26N6O. Calculated, %: C 64.38;
H 7.39; N 23.71.
N,N-Diethyl-5-methyl-7-phenyl-4,7-dihydro-
tetrazolo[1,5-a]pyrimidine-6-carboxamide (IIa).
Yield 1.44 g (46%), mp 267–268°C. IR spectrum, ν,
1
cm–1: 1600 (C=C), 1675 (C=O), 3150 (NH). H NMR
spectrum, δ, ppm: 0.90 m (6H, CH3CH2), 1.86 s (3H,
5-CH3), 3.05 m (4H, NCH2), 6.43 s (1H, 7-H), 7.35 m
(5H, C6H5), 10.50 s (1H, NH). Found, %: C 61.42,
61.56; H 6.38, 6.48; N 26.85, 26.92. C16H20N6O. Cal-
culated, %: C 61.52; H 6.45; N 26.90.
The IR spectra were recorded on a Specord M-80
spectrometer from samples dispersed in mineral oil.
The 1H NMR spectra were measured from solutions in
DMSO-d6 on a Bruker 500 instrument (500.13 MHz)
using tetramethylsilane as internal reference. The mass
spectrum (electron impact, 70 eV) was obtained on
a Finnigan MAT INCOS-50 mass spectrometer.
7-(4-Chlorophenyl)-N,N-diethyl-5-methyl-4,7-di-
hydrotetrazolo[1,5-a]pyrimidine-6-carboxamide
(IIb). Yield 1.25 g (36%), mp 244–246°C. IR spec-
trum, ν, cm–1: 1600 (C=C), 1660 (C=O), 3150 (NH).
1H NMR spectrum, δ, ppm: 0.75 m (6H, CH3CH2),
1.80 s (3H, 5-CH3), 3.04 m (4H, NCH2), 6.30 s (1H,
7-H), 7.00 m (4H, C6H4), 10.30 s (1H, NH). Found, %:
C 55.35, 55.54; H 5.43, 5.56; N 24.15, 24.28.
C16H19ClN6O. Calculated, %: C 55.41; H 5.52;
N 24.23.
REFERENCES
1. Gein, V.L., Levandovskaya, E.B., Nosova, N.V., Vakh-
rin, M.I., Kriven’ko, A.P., and Aliev, Z.G., Russ. J. Org.
Chem., 2007, vol. 43, p. 1096.
N,N-Diethyl-7-(3-fluorophenyl)-5-methyl-4,7-di-
hydrotetrazolo[1,5-a]pyrimidine-6-carboxamide
(IIc). Yield 1.39 g (42%), mp 224–226°C. IR spec-
2. Zhidovinova, M.S., Fedorova, O.V., Rusinov, G.L., and
Ovchinnikova, I.G., Izv. Ross. Akad. Nauk, Ser. Khim.,
2003, p. 1677.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 6 2009