A new approach to the synthesis of polyfunctionally substituted 1,8-naphthyridin-2-one derivatives from 6-azidopyridones: A novel thermal decomposition to 6-aminopyridones

Article abstract of DOI:10.1055/s-2001-9749

Azidation of the chloroaldehyde 2, which was obtained from the 6-hydroxy-2-pyridones 1, afforded the 6-azido-2-pyridories 3. Compound 3 can be converted to the corresponding 6-amino-2-pyridones 5, by the reaction with triphenylphosphine via phosphazenes and subsequent hydrolysis (Staudinger reaction). This obtained amine 5 reacts with ethyl cyanoacetate in an ethanolic solution containing piperidine to give 7-amino-6-carbethoxy-3-cyano-1,4-dimethyl-1,8-naphthyridin-2(1H)-one (9). Reaction of 9 with dimethylformamide dimethyl acetal, triethylorthoformate and hydrazine hydrate furnished the new 1,8-naphthyridin-2-ones 10, 11 and 12, respectively, in good yields. On the other hand, refluxing 9 with piperidine or morpholine, as secondary amines, did not afford the corresponding 1,8-naphthyridin-2-ones 13, but instead it undergoes a thermal decomposition under these reaction conditions to yield the unexpected 6-amino-3-cyano-1,4-dimethyl-pyridin-2(1H)-one (14).

Full text of DOI:10.1055/s-2001-9749

PAPER
103
A New Approach to the Synthesis of Polyfunctionally Substituted
1,8-Naphthyridin-2-one Derivatives from 6-Azidopyridones: A Novel Thermal
Decomposition to 6-Aminopyridones
Ramadan Ahmed Mekheimer
Department of Chemistry, Faculty of Science, El-Minia University, El-Minia 61519, AR Egypt
E-mail: r.mekh@scc-alph1.minia.eun.eg
Received 2 June 2000
the mild reaction conditions, good yields and chemoselec-
Abstract: Azidation of the chloroaldehyde 2, which was obtained
tivity of Staudinger reaction,6 we have applied this reac-
tion in our work to convert the azidopyridones 3 to the
corresponding aminopyridones 5, which are considered to
from the 6-hydroxy-2-pyridones 1, afforded the 6-azido-2-pyri-
dones 3. Compound 3 can be converted to the corresponding 6-ami-
no-2-pyridones 5, by the reaction with triphenylphosphine via
phosphazenes and subsequent hydrolysis (Staudinger reaction). be very important intermediates for the synthesis of the
This obtained amine 5 reacts with ethyl cyanoacetate in an ethanolic
solution containing piperidine to give 7-amino-6-carbethoxy-3-cy-
ano-1,4-dimethyl-1,8-naphthyridin-2(1H)-one (9). Reaction of 9
aminopyridones 5 show that the three steps sequence via
with dimethylformamide dimethyl acetal, triethylorthoformate and
hydrazine hydrate furnished the new 1,8-naphthyridin-2-ones 10,
desired polyfunctionally substituted 1,8-naphthyridin-2-
ones 9. An examination of other possible methods to the
the phosphazene 4 is a superior method to obtain the de-
sired products. Aminopyridones 5 cannot be prepared by
direct amination of chloropyridones 2 due to numerous
competing side reactions of other functional groups. In
continuation of our work concerning the synthesis and
biological evaluation of new heterocycles containing the
pyridine moiety,8-11 we wish to report herein our findings
on a novel, efficient and convenient procedure for the syn-
thesis of new polyfunctionally substituted 1,8-naphthyri-
din-2-ones, which are often difficult to obtain by
alternative routes, utilizing for the first time azidopyri-
dones as starting materials.
11 and 12, respectively, in good yields. On the other hand, refluxing
9 with piperidine or morpholine, as secondary amines, did not af-
ford the corresponding 1,8-naphthyridin-2-ones 13, but instead it
undergoes a thermal decomposition under these reaction conditions
to yield the unexpected 6-amino-3-cyano-1,4-dimethyl-pyridin-
2(1H)-one (14).
Key words: new synthesis, 1,8-naphthyridin-2-ones, thermal de-
composition, 6-amino-3-cyano-1,4-dimethyl-pyridin-2(1H)-one
The discovery of the older quinolones, such as Nalidixic
acid (1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyri-
dine-3-carboxylic acid), that have been used for the treat-
ment of a wide variety of infection diseases, led to the
synthesis of many 1,8-naphthyridin-5-one derivatives in-
cluding the potent antibacterial Enoxacin.1,2 Recently,
these drugs were reported to induce hypoglycemia3 and to
be inhibitors of the aldose reductase enzyme.4
Our synthesis began with the preparation of 3-cyano-6-
hydroxy-1,4-dimethyl-pyridine-2(1H)-one (1), which was
obtained from a mixture of ethyl cyanoacetate, ethyl ace-
toacetate and methylamine in ethanol under reflux with
piperidine as catalyst according to a literature method.12
Chlorination of 1 by a milder chlorination method using
phosphoryl chloride and dimethylformamide (Vilsmeier
reagent) led to the isolation of 6-chloro-3-cyano-5-
formyl-1,4-dimethyl-pyridin-2(1H)-one (2) with the suc-
cess that the 1-methyl group was not cleaved. Azidation of
the chloroaldehyde 2 with sodium azide in methanol at
room temperature afforded the corresponding azidopyri-
dones 3. The IR spectrum of 3 showed an absorption band
at 2140 cm-1 due to azide group. Treatment of 3 with one
equivalent of triphenylphosphine in dry toluene at room
temperature for 30 minutes gave 6-[(triphenylphosphora-
nylidene)amino]pyridones 4. Acid hydrolysis of 4 with a
mixture of acetic acid/water (1:1) provided the corre-
sponding 6-aminopyridone derivative 5, in excellent
yield, (Scheme 1). Structural proof of 5 rests on elemental
analysis and spectroscopic data. The IR spectrum showed
absorption bands at 3350 cm-1 and 3200 cm-1 correspond-
ing to amino group (NH2). In the 1H NMR spectrum of 5,
a singlet at d = 8.24 ppm for the amino group (NH2) at
C-6 is observed together with the signals of other groups
(see Experimental).
This pharmaceutical importance was the reason to devel-
op a new efficient general procedure for the synthesis of
hitherto unknown polyfunctionally substituted 1,8-naph-
thyridin-2-one derivatives in order to obtain new hypogly-
cemic agents. A literature search revealed that such
polyfunctionally substituted 1,8-naphthyridin-2-ones of
type 9 are completely unknown. Although different syn-
thetic methods to prepare these heterocyclic systems have
been reviewed,2,5 to the best of our knowledge, their syn-
thesis from azidopyridones has not been reported. Due to
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104
R. A. Mekheimer
PAPER
Scheme 1
As the synthesis of new polyfunctionally substituted
1,8-naphthyridin-2-one ring system is the main target of
this program, we therefore decided to investigate the reac-
tion of o-aminoaldehyde 5 with active methylenes with
the hope of obtaining the interesting 1,8-naphthyridin-2-
one ring system 9. Thus, for example, treatment of com-
pound 5 with ethyl cyanoacetate and piperidine in reflux-
ing ethanol for 15 minutes produced a solid product which
was identified as 7-amino-6-carbethoxy-3-cyano-1,4-
dimethyl-1,8-naphthyridin-2(1H)-one (9), in 92% yield,
(Scheme 2). The other possible structure 8 was readily
ruled out as the reaction product on the basis of analytical
and spectroscopic data. The IR spectrum of the reaction
product showed the presence of an amino function (NH2)
at 3400 cm-1 , 3330 cm-1 and 3250 cm-1 and an ester car-
bonyl at 1710 cm-1. The 1H NMR spectrum displayed the
absence of a singlet at d = 11.66 ppm,13 assignable to the
pyridine NH; the presence of a triplet (d = 1.26 ppm) and
a quartet (d = 4.24 ppm), assigned to an ethoxy group at 6-
position; and a singlet at d = 8.22 ppm that integrated for
two protons, assigned to an amino function (NH2) at C-7.
Moreover, the structure assigned for this reaction product
9 was fully supported by its mass spectrum, which showed
a molecular formula C14H14N4O3 (M+ 286) and allowed us
to discard the other possible structure 8. Compound 9 was
assumed to be formed via addition of an exocyclic amino
function to the cyano group of ethyl cyanoacetate to form
the acyclic intermediate 7, which underwent intramolecu-
lar condensation by loss a molecule of water to give 9. Al-
ternatively, addition of an exocyclic amino function to the
carbonyl group in ethyl cyanoacetate, followed by a loss
of a molecule of ethanol, to form the acyclic intermediate
6 will lead to the formation of 8 (Scheme 2).
Scheme 2
dimethylaminomethylene)amino]-1,4-dimethyl-1,8-naph-
thyridin-2(1H)-one (10), Scheme 3. Thus, the IR spectrum
revealed no absorption for amino group. The H NMR
1
spectrum showed the absence of an amino group signal,
and the presence of three singlets attributable to the two
methyl groups [-N(CH3)2] and methine proton (-N=CH) at
d = 3.08 ppm, 3.18 ppm and 8.28 ppm, respectively, in ad-
dition to the signals of other groups (see Experimental).
Meanwhile, refluxing 9 with triethylorthoformate for 8
hours yielded the corresponding ethoxymethyleneamino
derivative 11, in 73% yield. The structure of the isolated
product was confirmed on the basis of its elemental anal-
ysis and spectral data (see Experimental). 1,8-Naphthyri-
din-2-ones 9 also reacted with hydrazine hydrate in
refluxing ethanol for 10 hours to give a good yield
of
7-amino-6-carboxhydrazide-3-cyano-1,4-dimethyl-
1,8-naphthyridin-2(1H)-one (12), (Scheme 3).
The foregoing results and our interest to prepare new de-
rivatives of 1,8-naphthyridin-2-ones of type 13 prompted
us to investigate the behaviour of 9 towards secondary
amines. We envisaged that the reaction of 9 with piperi-
dine or morpholine would lead to the formation of the cor-
responding 1,8-naphthyridin-2-ones 13. Interestingly,
however, an unexpected new compound, 6-amino-3-cy-
ano-1,4-dimethyl pyridine-2(1H)-one 14, was obtained as
the sole isolated product (Scheme 4). To the best of our
knowledge, this reaction seems to be the first example of
the direct conversion of 1,8-naphthyridin-2-ones into
6-aminopyridones. A literature survey revealed that only
one compound of type 14, 6-amino-1-butyl-3-cyano-4-
methyl-pyridone-2(1H)-one, has been recently reported:
it was obtained by reacting 6-chloropyridones with anhy-
drous ammonia in a pressure reactor at 20 °C for
Since our interest is in developing a synthetic approach
with a view to synthesize new derivatives of the interest-
ing 1,8-naphthyridin-2-ones, compound 9, a good precur-
sor for this purpose, was thus investigated. Reaction of 9
with N,N-dimethylformamide dimethyl acetal (DMFD-
MA) in dry toluene at reflux temperature for 20 minutes
afforded a yellow product. On the basis of elemental
analysis and spectral data, the structure of the reaction
product was confirmed as 6-carbethoxy-3-cyano-7-[(N,N-
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A New Approach to the Synthesis of Polyfunctionally Substituted 1,8-Naphthyridin-2-one Derivatives
105
tion of 14 is assumed to proceed via an initial nucleophilic
attack by adventitious water on C-7 of 9A, tautomer of 9,
to form the non-isolable acyclic intermediate 15, which is
in equilibrium with the tautomer 16. Further nucleophilic
attack by another molecule of H2O on the activated double
bond in 16 to yield intermediate 17 was followed by a pro-
ton shift and intramolecular rearrangement to give the fi-
nal product 14 and the corresponding ester 18 (Scheme 5).
Attempts to detect or isolate compound 18 or any other
products were unsuccessful. Presumably, compound 18 is
thermally unstable and the thermal decomposition of 18
under these reaction conditions prevented its isolation. On
heating compound 9 in solvents such as DMF, bromoben-
zene, high-boiling benzene derivatives, and 1,2-dichlo-
robenzene, for extended periods, a high stability was
observed and the reaction failed to yield 14. On the basis
of these results, it may be concluded that the use of pipe-
ridine or morpholine, as a basic reagent, facilitates the
opening of the pyridine ring in 9.
Scheme 3
16 hours.14 Thus this conversion is considered to be a con-
venient and efficient procedure for the synthesis of 1-
alkyl-6-aminopyridones. The identity of compound 14
was supported by correct elemental analysis and mass
spectra as well as the IR and 1H NMR spectra, which were
compatible with the assigned structure. For example, its
mass spectrum showed a molecular ion peak at m/z = 163,
and the elemental analysis confirmed the molecular for-
mula of this compound as C8H9N3O. The IR spectrum of
14 showed no absorption band for ester carbonyl group
but absorption bands for the NH2 and CN groups were ob-
served at 3350 cm-1, 3200 cm-1 and 2200 cm-1, respec-
tively. Furthermore, the 1H NMR gave strong evidence for
the formation of compound 14. The data confirmed the
absence of the ethoxy group at C-6 and the H-5 proton of
1,8-naphthyridin-2-ones 9, the presence of two singlets at
d = 5.57 ppm and 7.41 ppm attributable to the H-5 proton
and the amino group at C-6, respectively, in addition to
signals due to two methyl groups in their expected posi-
tions (see Experimental).
Scheme 5
In summary, we have discovered a facial and efficient
synthetic route to new 1,8-naphthyridin-2-one system, of
expected biological interest, by utilizing simple reaction
sequences starting from the 6-azidopyridones. To the best
of our knowledge, this is the first time that such cleavage
of the 1,8-naphthyridin-2-one ring system to the corre-
sponding aminopyridones has been described.
Scheme 4
All mps are uncorrected. IR spectra were recorded in KBr disks us-
ing a Shimadzu 470 spectrophotometer. 1H NMR spectra were re-
corded on a Bruker AM400 spectrometer at 400 MHz, with DMSO-
d6 as solvent and TMS as internal standard; chemical shifts (d) are
reported in ppm. Mass spectra were measured on a GCMS-
The probable mechanism leading to the formation of
6-aminopyridones 14 is outlined in Scheme 5. The forma-
Synthesis 2001, No. 1, 103–107 ISSN 0039-7881 © Thieme Stuttgart · New York

106
R. A. Mekheimer
PAPER
QP1000EX mass spectrometer. Microanalyses were performed at
the Microanalytical Data Unit, Cairo University.
1H NMR (DMSO-d6): d = 2.44 (s, 3H, CH3), 3.28 (s, 3H, CH3), 8.24
(s, 2H, NH2), 9.96 (s, 1H, CHO).
Anal. Calcd. for C9H9N3O2 (191.18): C, 56.54; H, 4.74; N, 21.98.
Found: C, 56.73; H, 4.82; N, 21.87.
6-Chloro-3-cyano-5-formyl-1,4-dimethyl-pyridin-2(1H)-one (2)
Phosphoryl chloride (1.31 g, 8.54 mmol) was added dropwise to
cooled dimethylformamide (0.223 g, 3.05 mmol) at 0 °C, and the
temperature of the reaction mixture was maintained at 0-5 °C.
6-Hydroxy-pyridin-2-ones 1 (0.20 g, 1.22 mmol) was added and the
reaction mixture was stirred at 65-70 °C for 7 h. After cooling, the
reaction mixture was poured into cold H2O. The obtained precipi-
tate was filtered, washed with H2O, dried and recrystallized from
EtOH to give compound 2 as yellow crystals.
7-Amino-6-carbethoxy-3-cyano-1,4-dimethyl-1,8-naphthyri-
din-2(1H)-one (9)
A mixture of 5 (0.90 g, 4.71 mmol), ethyl cyanoacetate (5.32 g,
47.1 mmol), piperidine (1.60 g, 18.82 mmol) and absolute EtOH
(25 mL) was heated at reflux. After 15 min the mixture was filtered,
the solid was washed with EtOH, dried, and recrystallized from
EtOH to give compound 9 as yellow crystals.
Yield: 0.190 g (74%); mp: 179-180 °C.
IR (KBr): n = 2220 (CN), 1670 (C=O) cm-1.
1H NMR (DMSO-d6): d = 2.61 (s, 3H, CH3), 3.65 (s, 3H, CH3),
10.17 (s, 1H, CHO).
MS: m/z (%) = 212 (M+, 7), 210 (M+, 14), 184 (55), 182 (100), 147
(55), 119 (39), 78 (53).
Yield: 1.24 g (92%); mp: 262-264 °C.
IR (KBr): n = 3400, 3330, 3250 (NH2), 2200 (CN), 1710 (C=O,
ester) cm-1.
1H NMR (DMSO-d6): d = 1.26 (t, 3H, J = 7 Hz, CH3), 2.33 (s, 3H,
CH3), 3.32 (s, 3H, CH3), 4.24 (q, 2H, J = 7 Hz, CH2), 8.06 (s, 1H,
H-5), 8.22 (s, 2H, NH2).
Anal. Calcd. for C9H7ClN2O2 (210.66):C, 51.31; H, 3.35; Cl, 16.85;
N, 13.30. Found: C, 51.15; H, 3.42; Cl, 16.97; N, 13.48.
MS: m/z (%) = 287 (M+1, 9), 286 (M+, 11), 241 (8), 213 (100), 143
(5), 129 (3), 66 (5).
Anal. Calcd. for C14H14N4O3 (286.27): C, 58.73; H, 4.93; N, 19.57.
Found: C, 58.56; H, 5.06; N, 19.47.
6-Azido-3-cyano-5-formyl-1,4-dimethyl-pyridin-2(1H)-one (3)
Sodium azide (0.062 g, 0.95 mmol) was added to a solution of 2
(0.2 g, 0.95 mmol) in MeOH (10 mL) and the mixture was stirred
for 2 h at r.t. (25 °C). Then the reaction mixture was poured into
H2O, and the obtained clear solution was extracted with CHCl3. The
extract was dried (Na2SO4) and evaporated to dryness. The resulting
solid product was collected by filtration, dried and recrystallized
from MeOH to yield compound 3 as yellow crystals.
6-Carbethoxy-3-cyano-7-N-(N,N-dimethylaminomethyl-
ene)imino-1,4-dimethyl-1,8-naphthyridin-2(1H)-one (10)
N,N-Dimethylformamide dimethyl acetal (0.120 g, 1 mmol) was
added to a suspension of 9 (0.143 g, 0.5 mmol) in dry toluene
(5 mL) and the mixture was refluxed for 20 min. After concentration
and cooling to r.t., the resulting solid product was filtered off, dried,
and recrystallized from toluene to give compound 10 as yellow
crystals.
Yield: 0.165 g (80%); mp: 144 °C (dec.).
IR (KBr): n = 2200 (CN), 2140 (N3), 1670 (C=O) cm-1.
1H NMR (DMSO-d6): d = 2.58 (s, 3H, CH3), 3.61 (s, 3H, CH3),
10.15 (s, 1H, CHO).
Yield: 0.130 g (76%); mp: 188-190 °C.
IR (KBr): n = 2980, 2920, 2900 (CH, aliphatic), 2200 (CN), 1730
(C=O, ester) cm-1.
Anal. Calcd. for C9H7N5O2 (217.18): C, 49.77; H, 3.25; N, 32.25.
Found: C, 49.65; H, 3.29; N, 32.08.
1H NMR (DMSO-d6): d = 1.28 (t, 3H, J = 7 Hz, CH3), 2.34 (s, 3H,
CH3), 3.08 (s, 3H, CH3), 3.18 (s, 3H, CH3), 3.36 (s, 3H, CH3), 4.28
(q, 2H, J = 7 Hz, CH2), 8.15 (s, 1H, H-5), 8.28 (s, 1H, -N = CH-).
3-Cyano-5-formyl-1,4-dimethyl-6-[(triphenylphosphora-
nylidene)amino]pyridin-2(1H)-one (4)
Anal. Calcd. for C17H19N5O3 (341.35): C, 59.81; H, 5.61; N, 20.52.
Found: C, 59.59; H, 5.70; N, 20.38.
Triphenylphosphine (0.242 g, 0.92 mmol) was added to a suspen-
sion of 6-azidopyridones 3 (0.20 g, 0.92 mmol) in dry toluene
(10 mL) and the mixture was stirred for 30 min at r.t. The solvent
was evaporated to dryness in vacuo. MeOH (3 mL) was added to the
remaining oily residue with scratching. The precipitated solid prod-
uct was isolated by suction, washed with MeOH, dried and recrys-
tallized from toluene to give compound 4 as colorless crystals.
6-Carbethoxy-3-cyano-7-(ethoxymethyleneamino)-1,4-dimeth-
yl-1,8-naphthyridin-2(1H)-one (11)
A suspension of 9 (0.40 g, 1.40 mmol) in triethylorthoformate
(15 mL) was refluxed for 8 h with stirring. After evaporation of the
solvent under reduce pressure, the residue was triturated with EtOH.
The formed product was filtered off, dried, and recrystallized from
acetone to give compound 11 as yellow crystals.
Yield: 0.370 g (89%); mp: 260-261 °C.
IR (KBr): n = 3050 (ArH), 2200 (CN), 1670 (C=O) cm-1.
1H NMR (DMSO-d6): d = 2.36 (s, 3H, CH3), 3.46 (s, 3H, CH3),
7.62-7.76 (m, 15H, ArH), 10.08 (s, 1H, CHO).
Yield: 0.350 g (73%); mp: 144-145 °C.
IR (KBr): n = 2980, 2920, 2900 (CH, aliphatic), 2200 (CN), 1730
(C=O, ester) cm-1.
Anal. Calcd. for C27H22N3O2P (451.47): C, 71.83; H, 4.91; N, 9.31.
Found: C, 71.58; H, 4.99; N, 9.22.
1H NMR (DMSO-d6): d = 1.29 (t, 3H, J = 7 Hz, CH3), 1.49 (t, 3H,
J = 7 Hz, CH3), 2.35 (s, 3H, CH3), 3.37 (s, 3H, CH3), 4.29 (q, 2H,
J = 7 Hz, CH2), 4.48 (q, 2H, J = 7 Hz, CH2), 8.18 (s, 1H, H-5), 8.39
(s, 1H, -N = CH-).
6-Amino-3-cyano-5-formyl-1,4-dimethyl-pyridin-2(1H)-one (5)
Triphenylphosphoranylideneaminopyridones
4
(0.30
g,
0.67 mmol), HOAc (2 mL) and H2O (2 mL) were stirred for 15 min
at r.t.. The solvent was removed in vacuo and the resulting solid
product was collected by filtration, washed well with MeOH to re-
move Ph3PO, dried, and recrystallized from DMF to give compound
5 as colorless crystals.
Anal. Calcd. for C17H18N4O4 (342.33): C, 59.64; H, 5.30; N, 16.36.
Found: C, 59.85; H, 5.48; N, 16.23.
7-Amino-6-carboxhydrazide-3-cyano-1,4-dimethyl-1,8-naph-
thyridin-2(1H)-one (12)
Yield: 0.124 g (98%); mp: 312-314 °C (dec.).
IR (KBr): n = 3350, 3200 (NH2), 2200 (CN), 1680 (C=O) cm-1.
A mixture of 9 (0.40 g, 1.40 mmol) and hydrazine hydrate (80%,
1 mL) in EtOH (15 mL) was refluxed for 10 h. After cooling to r.t.,
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A New Approach to the Synthesis of Polyfunctionally Substituted 1,8-Naphthyridin-2-one Derivatives
107
the resulting solid product was filtered off, washed with EtOH,
dried, and purified by boiling in DMF to give compound 12 as yel-
low crystals.
References
(1) Dekker, M. In The New Generation of Quinolones; Siporin,
C.; Heifetz, C. L.; Domagala, J. M., Eds.; New York, 1990.
(2) Bouzard, D. In Recent Progress in the Chemical Synthesis of
Antibiotics: Recent Advances in the Chemistry of Quinolones;
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(3) Maeda, N.; Tamagawa, T.; Niki, I.; Miura, H.; Ozawa, K.;
Watanabe, G.; Nogogaki, K.; Uemura, K.; Iguchi, A. Br. J.
Pharmacol. 1996, 117, 372.
Yield: 0.30 g (79%); mp: 352 °C (dec.).
IR (KBr): n = 3400, 3300, 3200 (NH, NH2), 2200 (CN), 1660
(C=O) cm-1.
1H NMR (DMSO-d6): Insoluble in commonly used NMR solvents.
Anal. Calcd. for C12H12N6O2 (272.26): C, 52.93; H, 4.44; N, 30.87.
Found: C, 52.79; H, 4.70; N, 30.69.
(4) Büyükbingoel, E.; Net, D.; Klopman, G. Arch. Pharm. 1994,
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6-Amino-3-cyano-1,4-dimethyl-pyridin-2(1H)-one (14)
A mixture of 9 (0.30 g, 1.05 mmol) and morpholine or piperidine
(5 mL) was heated under reflux for 3 h. After concentration, H2O
was added and the resulting solid product was collected by filtra-
tion, washed with H2O, dried, and recrystallized from MeOH to
give compound 14 as colorless crystals.
Yield: 0.110 g (64%); mp: 286-287 °C (dec.).
IR (KBr): n = 3350, 3200 (NH2), 2200 (CN), 1650 (C=O) cm-1.
1H NMR (DMSO-d6): d = 2.09 (s, 3H, CH3), 3.27 (s, 3H, CH3), 5.57
(s, 1H, H-5), 7.41 (s, 2H, NH2).
MS: m/z (%) = 164 (M+1, 10), 163 (M+, 100), 147 (1), 135 (83), 122
(9), 120 (35), 93 (15), 78 (31).
Anal. Calcd. for C8H9N3O (163.17): C, 58.88; H, 5.56; N, 25.75.
Found: C, 58.68; H, 5.51; N, 25.59.
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Article Identifier:
1437-210X,E;2001,0,01,0103,0107,ftx,en;P04200SS.pdf
Synthesis 2001, No. 1, 103–107 ISSN 0039-7881 © Thieme Stuttgart · New York