A new thermal study of the reaction of 6-azidopyridones with different amines and hydrazines

Article abstract of DOI:10.1002/jhet.5570450107

(Chemical Equation Presented) Reacting of 6-azidopyridone derivatives 1 with o-phenylenediamine (2a) in chloroform at room temperature afforded the new azidopyridones 3. However, its fusion with 2a,b at 100-110°C gave the interesting pyrido[2,3-b][1,5]diazepines 4a,b. Alternatively, compound 4a could also be obtained by heating azidopyridones 3 at 100-110°C. When compound 1 was allowed to react with hydrazines 7a-d at room temperature it gave the corresponding azido compounds 8a-d. Fusion of 1 with Phenylhydrazine (7d) at 140-160°C afforded the new aminopyridones 10. The 6-azidopyridones 1 could also be converted to the corresponding 6-alkylaminopyridones 15a-d by reaction with an excess of alkylamines at room temperature.

Full text of DOI:10.1002/jhet.5570450107

Jan-Feb 2008
97
A New Thermal Study of The Reaction of 6-Azidopyridones With
Different Amines and Hydrazines
Ramadan Ahmed Mekheimer*, Afaf Mohamed Abd El-Hameid and Kamal U. Sadek
Department of Chemistry, Faculty of Science, EL-Minia University, El-Minia 61519, Egypt
*E-mail: rmekh@yahoo.com
Received December 1, 2006
H2N
CH3
Y
NC
Y
N
2
fusion
100-110oC
O
N
N
CH3
CH3
H
NC
O
CHO
N3
4
N
CH3
CH3
1
NC
O
CH=NNHR
N3
RNHNH2
CHCl3/RT
N
CH3
8
Reacting of 6-azidopyridone derivatives 1 with o-phenylenediamine (2a) in chloroform at room
temperature afforded the new azidopyridones 3. However, its fusion with 2a,b at 100-110˚C gave the
interesting pyrido[2,3-b][1,5]diazepines 4a,b. Alternatively, compound 4a could also be obtained by
heating azidopyridones 3 at 100-110˚C. When compound 1 was allowed to react with hydrazines 7a-d at
room temperature it gave the corresponding azido compounds 8a-d. Fusion of 1 with phenylhydrazine (7d)
at 140-160˚C afforded the new aminopyridones 10. The 6-azidopyridones 1 could also be converted to the
corresponding 6-alkylaminopyridones 15a-d by reaction with an excess of alkylamines at room
temperature.
J. Heterocyclic Chem., 45, 97 (2008).
novel polyfunctionally substituted pyridines of expected
significant biological activity, which are often difficult to
obtain by alternative routes. Although a number of studies
in the chemistry of azide compounds have been carried
out [20-23], to the best of our knowledge, the title studies
have not been reported so far.
INTRODUCTION
Many pyridine compounds and their derivatives have
recently occupied an important place in synthetic organic
chemistry due to their pharmacological and therapeutic
properities [1-5]. Moreover, 2-pyridones represent an
important class of pyridine derivatives. A number of
compounds with this substitution pattern are found in
natural products with biological activity, such as tenellin
[6] and sambutoxin [7]. In recent years, 2-pyridones have
attracted considerable attention due to their promising
features as an important core structure for the develop-
ment of biologically active compounds [8]. In addition,
pharmaceuticals with the 2-pyridone skeleton have
emerged as antitumor, antifungal, antiviral, antithrom-
botic, antioxidant, antidiabetic and antimicrobial agents
[9-14]. Owing to the importance of this class of hetero-
cycle and also as part of our research program dealing
with the synthesis of pharmacologically interesting new
heterocycles, particulary those containing the pyridine
moiety [15-19], herein we describe the first study on the
reaction of 6-azidopyridones 1 [15] with aromatic and
aliphatic amines and hydrazines in order to synthesize
RESULTS AND DISCUSSION
In our studies, we first investigated the reaction of 6-
azidopyridones 1 with aromatic amines such as o-
phenylenediamine (2a) and o-aminothiophenol (2b).
Reaction of azidopyridones 1 with equimolar amount of
o-phenylenediamine (2a), for example, in CHCl3 for 1 h
at room temperature gave the corresponding azido-
pyridones 3. However, fusion of 1 with 2a,b at 100-110˚C
for 10 min., did not give the expected tricycle 5, but rather
the previously unknown tricyclic system pyrido[2,3-b]-
[1,5]benzodiazepines 4a,b. Alternatively, compound 4a
could also be obtained by heating compound 3 at 100-
110˚C for 5 min. (Scheme 1). The structures of 4a,b were
confirmed as the reaction products from their IR, NMR
and correct elemental analyses as well as mass spectra.
Thus, for example, the IR spectrum of 4a revealed the

98
R. A. Mekheimer, A. Mohamed A. El-Hameid and K. U. Sadek
Vol 45
Experimental), confirming its presumed structure.
Analytical data are in accordance with the proposed
structure for compound 4a. Formation of 4a can be
accounted for by condensation of 1 with 2a to give the
ring-opened intermediate 3, with loss molecular nitrogen
to give nitrene intermediate 6. Subsequent intramolecular
cyclization leads to the final product 4a (Scheme 2).
Scheme 1
H2N
CH=N
CH3
NC
O
2a
RT
N
N3
CH3
(85%)
3
H2N
Y
Attention was next turned to investigate the reactivity
of azidopyridones 1 with some hydrazines at different
temperature. At room temperature, the reaction of
azidopyridones 1 with equimolar amounts of hydrazines
7a-d in CHCl3 for 2 h provided the corresponding new
azido compounds 8a-d in high yields (63-86%). However,
when the reaction conditions were changed and
azidopyridones 1 was treated with the same hydrazines
under heating, we found that all trials to heat compound 1
with hydrazines 7a,b were failed because a strong
explosion happened at the beginning of heating.
Moreover, our efforts to react 1 with 7c at high
temperature, whether in the absence or presence of
solvent, were unsuccessful and gave a number of products
which could not be isolated. Interestingly, heating
equimolar amounts of 1 and phenylhydrazine (7d) at 140-
160˚C for 10 min. did not give the expected fused pyra-
zolopyridones 11, instead the novel 6-aminopyridones 10
was formed as evidenced from spectral data. To obtain
unequivocal evidence for the structure of compound 10, it
was alternatively synthesized from the azide 8d by
reduction of the azide moiety at C-6 in 8d with sodium
dithionite at room temperature. The mechanism of the
formation of 10 from the reaction of 1 with 7d is assumed
to proceed via the formation of the azidopyridones 8d,
with loss one molecule of nitrogen to form the nitrene
intermediate 9, which then abstracts hydrogen, possibly
from the hydrogen donor phenylhydrazine, to give the
final product 10, as depicted in Scheme 3.
CH3
fusion
100-110oC
NC
O
CHO
N3
2a,b
CH3
N
NC
O
Y
N
CH3
1
N
N
CH3
H
4a,b (71-82%)
fusion
100-110oC
CH3
NC
O
N
2,4
Y
N
Y
a
b
NH2
SH
CH3
5
absence of the azido and aldehydic carbonyl groups and
the presence of absorption bands at ꢀ 3375 and 3200 cm-1
1
due to amino functions (NH, NH2). The H nmr spectrum
of 4a showed besides the signals due to aromatic and two
methyl protons, three singlet signals at ꢀ 7.54, 7.82 and
12.35 ppm attributable to NH2, CH at C-5 and diazepine
NH, respectively. Moreover, the structure of 4a has been
established by its 13C nmr spectrum which showed signals
at 164.70 (CO), 160.62 (C-4), 155.72 (C-5), 149.11 (C-7),
143.33 (C-11a), 140.04 (C-10a), 129.06 (C-9), 125.41(C-
6a), 116.37 (C-4a), 115.42 (CN), 114.32 (C-3), 111.22
(C-10), 110.52 (C-8), 29.14 (N-CH3), 20.19 (CH3 at C-4).
Furthermore, the mass spectrum this product shows the
molecular ion m/z 279 (M+, 100) and other peaks (see
In conjunction with this study, we investigated the
behavior of the reaction of azidopyridones 1 with primary
alkyl amines. Treatment of compound 1 with an excess of
alkylamines 12a-d in EtOH at room temperature for 3 h
afforded the hitherto unknown 6-alkylamino-5-formyl-
1,4-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitriles
15a-d, which formed via the nucleophilic substitution of
the azido group at pyridinic C-6 in 1 with amino group, in
moderate and good yields (59-66%) (Scheme 4).
Alternative uncyclized structure 13 could be eliminated
on the basis of the disappearance of the azido signal and
the presence of CHO and NH signals in the ir spectra,
Scheme 2
H2N
CH3
CH3
NC
O
CHO
N3
NC
O
CH=N
N3
2a
- H2O
N
N
CH3
CH3
1
3
- N2
1
while H nmr spectra, elemental analyses as well as mass
CH3
H2N
CH=N
CH3
spectra eliminated the linearly fused system 14. The data
used to characterize these prepared compounds 15a-d are
given in experimental.
NC
O
NH2
N
NC
O
N
N
N
N
CH3
H
In summary, we have presented for the first time, a
novel, simple and one-pot synthetic method for the
CH3
4a
6

Jan-Feb 2008
A New Thermal Study of The Reaction of 6-Azidopyridones
99
new examples of pyridone compounds, which are scarcely
represented in the literature. Further studies in our
laboratory aimed at the synthesis of a wide variety of
novel heterocycles containing the pyridine moiety,
utilizing 6-azidopyridones as the starting material, are in
progress.
Scheme 3
1
RNHNH2
7a-d
7d
fusion
140-160oC
- N2
CHCl3
RT
EXPERIMENTAL
CH3
CH3
NC
All melting points are uncorrected. ir spectra were recorded in
KBr disks using a Schimadzu 470 spectrophotometer. Nmr
spectra were recorded on Bruker AM 400 spectrometer at 400
MHz with DMSO-d6 and CDCl3 as solvents and tetramethyl-
silane (TMS) as an internal standards. Chemical shifts (ꢀ) are
reported in ppm downfield of TMS. Mass spectra were
NC
O
CH=NNHR
N3
CH=NNHPh
N
N
O
N
CH3
CH3
8a-d (63-86%)
9
measured on
a
GCMS-QP1000EX mass spectrometer.
Microanalyses were performed at the Microanalytical Data Unit,
Cairo University.
8d
[2H]
Na2S2O4/
MeOH
RT
5-[(2-Aminophenylimino)methyl]-6-azido-1,4-dimethyl-2-
oxo-1,2-dihydropyridine-3-carbonitrile (3). A mixture of 1
(0.217 g, 1 mmol) and o-phenylenediamine (2a) (0.108 g, 1
mmol) in CHCl3 (5 ml) was stirred for 1 h at room temperature
(25˚C). The resulting solid product was filtered off, dried and
recrystallized from CHCl3 to afford 0.260 g (85%) of 3 as
reddish crystals, mp: 204-206˚C; ir (KBr): ꢀ 3450, 3350 (NH2),
CH3
CH3
NC
O
NC
CH=NNHph
NH2
N
NHPh
N
N
O
N
CH3
CH3
7,8
R
(87%)
10
11
a
b
c
d
H
1
2900 (aliph. CH), 2220 (CN), 2150 (N3), 1645 (CO) cm-1; H
CH3
PhCO
Ph
nmr (CDCl3): ꢀ 2.75 (s, 3H, CH3), 3.42 (s, 3H, CH3), 6.56 (s,
2H, NH2), 6.62-7.01 (m, 4Harom), 8.81 (s, 1H, CH); ms: m/z 280
(M+1-N2, 100), 279 (M+, 86), 265 (92), 250 (15), 119 (17), 105
(18), 92 (30), 76 (31). Anal. Calcd. for C15H13N7O (307.29): C,
58.63; H, 4.26; N, 31.90. Found: C, 58.47; H, 4.43; N, 31.79.
General procedure for the synthesis of 3-cyano-1,4-
dimethyl-7-substituted-pyrido[2,3-b][1,5]benzodiazepin-
2,6(1H,11H)-ones (4a,b). Route (A) for 4a,b: A mixture of 1
(0.217 g, 1 mmol) and 2a,b (1 mmol) in CHCl3 (5 ml) was
heated for 10 min. at 100-110˚C. After cooling to room
temperature, the resulting solid product was collected by
filtration, washed with EtOH, dried and recrystallized from
EtOH to afford 4a,b.
Scheme 4
CH3
NC
O
CH=NR
N3
N
CH3
13
CH3
RNH2
12a-d
RT
NC
O
Route (B) for compound 4a: Compound 3 (0.20 g, 0.65
mmol) was heated at 100-110˚C for 5 min. After cooling to
room temperature, the mixture was treated with MeOH. The
resulting solid product was collected by filtration and dried to
afford 4a.
1
N
R
N
N
CH3
14
7-Amino-3-cyano-1,4-dimethyl-pyrido[2,3-b][1,5]benzo-
diazepin-2,6(1H,11H)-ones (4a). This compound was obtained
as brownish crystals, yield: [0.200 g (72%) (route A) and 0.150
g (82%) (route B)]; mp: 276-278˚C; ir (KBr): ꢀ 3375, 3200 (NH,
12, 15
R
CH3
a
b
c
d
isopropyl
butyl
isobutyl
cyclohexyl
NC
O
CH=O
NHR
N
1
NH2), 2200 (CN), 1640 (CO) cm-1; H nmr (DMSO-d6): ꢀ 2.59
CH3
(s, 3H, CH3), 3.43 (s, 3H, CH3), 7.10-7.13 (m, 3Harom), 7.54 (br
s, 2H, NH2) 7.82 (s, 1H, CH), 12.35 (br s, 1H, NH); ms: m/z 281
(M+2, 19), 280 (M+1, 97), 279 (M+, 100), 264 (57), 249 (5), 234
(9), 208 (4), 133 (2), 118 (9), 105 (5), 91 (6), 75 (3). Anal.
Calcd. for C15H13N5O (279.28): C, 64.50; H, 4.69; N, 25.08.
Found: C, 64.62; H, 4.87; N, 25.19.
(59-66%)
15a-d
construction of different multiple substituted pyridone
derivatives, which might be used in many different areas.
Furthermore, the above route is very convenient for its
simplicity, the affordability of the starting materials and
good yields obtained and opens the way for synthesis of
3-Cyano-7-mercapto-1,4-dimethyl-pyrido[2,3-b][1,5]-
benzodiazepin-2,6(1H,11H)-ones (4b). This compound was
obtained as reddish crystals, yield: 0.210 g (71%); mp: 298-

100
R. A. Mekheimer, A. Mohamed A. El-Hameid and K. U. Sadek
Vol 45
300˚C; ir (KBr): ꢀ 3350 (NH), 2220 (CN), 1640 (CO) cm-1; H
nmr (DMSO-d6): ꢀ 2.90 (s, 3H, CH3), 3.47 (s, 3H, CH3), 7.36-
7.46 (m, 2Harom), 7.93 (d, 1Harom, J = 8 Hz), 8.02 (s, 1H, CH),
12.39 (br s, 1H, NH); ms: m/z 297 (M+1, 29), 296 (M+, 99), 281
(100), 264 (30), 238 (7), 148 (15), 136 (10), 135 (8), 121 (5),
108 (14), 76 (10), 57 (41). Anal. Calcd. for C15H12N4OS
(296.33): C, 60.79; H, 4.08; N, 18.90; S, 10.82. Found: C, 60.72;
H, 4.19; N, 18.79; S, 10.69.
1
MeOH (12 ml)-water (4 ml) mixture. Stirring was maintained at
room temperature (25˚C) for 5 h. Then, the reaction mixture was
poured into water. The precipitated solid product was collected
by filtration, washed well with water and dried to give [0.230 g
(82%) (route A) and 0.160 (87%) (route B)] of 10 as yellow
crystals, yield: mp: 278-280˚C; ir (KBr): ꢀ 3450, 3350, 3200
1
(NH, NH2), 2220 (CN), 1640 (CO) cm-1; H nmr (DMSO-d6): ꢀ
2.58 (s, 3H, CH3), 3.35 (s, 3H, CH3), 6.66 (t, 1Harom, J = 7 Hz),
6.90 (d, 2Harom, J = 8 Hz), 7.16 (t, 2Harom, J = 8 Hz), 7.57 (s, 2H,
NH2), 8.14 (s, 1H, CH), 10.07 (s, 1H, NH); ms: m/z 282 (M+1,
92), 281 (M+, 99), 265 (24), 190 (71), 189 (90), 146 (13), 135
(10), 119 (12), 93 (100), 92 (37), 77 (31). Anal. Calcd. for
C15H15N5O (281.30): C, 64.04; H, 5.38; N, 24.89. Found: C,
64.18; H, 5.21; N, 24.76.
General procedure for the synthesis of 5-arylhydrazono-
methyl-6-azido-1,4-dimethyl-2-oxo-1,2-dihydropyridine-3-
carbonitriles (8a-d). A mixture of 1 (0.217 g, 1 mmol) and
hydrazines 7a-d (1 mmol) in CHCl3 (5ml) was stirred for 2 h at
room temperature (25˚C). The resulting solid product was
filtered off, dried and recrystallized from CHCl3 to afford 8a-d.
It should be noticed that the reaction of compound 1 with
hydrazines 7 under heating may be explosive.
General procedure for the synthesis of 6-alkylamino-5-
formyl-1,4-dimethyl-2-oxo-1,2-dihydropyridine-3-carbo-
nitriles (15a-d). Alkylamines 12a-d (2 mmol) were added to
a
6-Azido-5-hydrazonomethyl-1,4-dimethyl-2-oxo-1,2-dihydro-
pyridine-3-carbonitrile (8a). This compound was obtained as
reddish crystals, yield: 0.150 g (65%); mp: 210-212˚C (dec.); ir
(KBr): ꢀ 3350, 3200 (NH2), 2200 (CN), 2150 (N3), 1640 (CO)
cm-1; 1H nmr (DMSO-d6): ꢀ 2.61 (s, 3H, CH3), 3.42 (s, 3H, CH3),
8.75 (s, 1H, CH), 10.00 (s, 2H, NH2). Anal. Calcd. for C9H9N7O
(231.20): C, 46.75; H, 3.92; N, 42.40. Found: C, 46.63; H, 3.78;
N, 42.52.
solution of compound 1 (0.217 g, 1 mmol) in dry EtOH and the
mixture was stirred for 3 h at room temperature. The resulting
solid product was collected by filtration, dried and recrystallized
from EtOH to give compounds 15a-d.
5-Formyl-6-isopropylamino-1,4-dimethyl-2-oxo-1,2-dihydro-
pyridine-3-carbonitrile (15a). This compound was obtained
as yellow crystals; yield: 0.150 g (64%); mp: 202-204˚C; ir
(KBr): ꢀ 3200 (NH), 2980, 2950 (aliph. CH), 2200 (CN), 1680
6-Azido-5-methylhydrazonomethyl-1,4-dimethyl-2-oxo-
1,2-dihydropyridine-3-carbonitrile (8b). This compound was
obtained as reddish crystals, yield: 0.155 g (63%); mp: 230-
232˚C (dec.); ir (KBr): ꢀ 3290 (NH), 2950, 2900 (aliph. CH),
1
(CO), 1640 (CO) cm-1; H nmr (CDCl3): ꢀ 1.42 (d, 6H, J = 6
Hz, 2CH3), 2.44 (s, 3H, CH3), 3.32 (s, 3H, CH3), 3.75 (m, 1H,
N-CH) 7.82 (d, 1H, J = 14 Hz, NH), 11.42 (s, 1H, CHO); ms:
m/z 234 (M+1, 70), 233 (M+, 78), 218 (63), 190 (12), 175 (3),
146 (4), 58 (21), 57 (100). Anal. Calcd. for C12H15N3O2
(233.26): C, 61.79; H, 6.48; N, 18.01. Found: C, 61.87; H,
6.35; N, 18.23.
1
2200 (CN), 2150 (N3), 1660 (CO) cm-1; H nmr (DMSO-d6): ꢀ
2.32 (s, 3H, CH3), 3.26 (d, 3H, J = 4 Hz, CH3), 3.42 (s, 3H,
CH3), 8.56 (s, 1H, CH), 10.02 (br s, 1H, NH). Anal. Calcd. for
C10H11N7O (245.23): C, 48.97; H, 4.52; N, 39.98. Found: C,
48.76; H, 4.65; N, 39.86.
6-Butylamino-5-formyl-1,4-dimethyl-2-oxo-1,2-dihydro-
pyridine-3-carbonitrile (15b).This compound was obtained as
yellow crystals, yield: 0.155 g (63%); mp: 176-178˚C. ir (KBr):
ꢀ 3200 (NH), 2950, 2900 (aliph. CH), 2200 (CN), 1670 (CO),
1640 (CO) cm-1; 1H nmr (CDCl3): ꢀ 0.95 (t, 3H, J = 7 Hz, CH3),
1.45 (m, 2H, CH2), 1.75 (m, 2H, CH2), 2.43 (s, 3H, CH3), 3.30
(s, 3H, CH3), 3.55 (q, 2H, J = 7 Hz, CH2), 7.81 (dd, 1H, J = 13,
2 Hz, NH), 11.25 (s, 1H, CHO); ms: m/z 248 (M+1, 55), 247 (M+,
58), 218 (7), 205 (82), 204 (100), 190 (7), 176 (6), 146 (6), 71
(59), 57 (8), 56 (46). Anal. Calcd. for C13H17N3O2 (247.29): C,
63.14; H, 6.93; N, 16.99. Found: C, 63.30; H, 6.79; N, 16.84.
6-Isobutylamino-5-formyl-1,4-dimethyl-2-oxo-1,2-dihydro-
pyridine-3-carbonitrile (15c).This compound was obtained as
yellow crystals; yield: 0.145 g (59%); mp: 180-182˚C; ir (KBr):
ꢀ 3300 (NH), 2970, 2900 (aliph. CH), 2200 (CN), 1670 (CO),
1640 (CO) cm-1; 1H nmr (CDCl3): ꢀ 0.99 (d, 6H, J = 6 Hz,
2CH3), 1.95 (m, 1H, CH), 2.39 (s, 3H, CH3), 3.30 (s, 3H, CH3),
3.33 (t, 2H, J = 7 Hz, CH2), 7.72 (t, 1H, J = 14 Hz, NH), 11.44
(s, 1H, CHO). Anal. Calcd. for C13H17N3O2 (247.29): C, 63.14;
H, 6.93; N, 16.99. Found: C, 63.03; H, 7.02; N, 16.87.
6-Azido-5-benzoylhydrazonomethyl-1,4-dimethyl-2-oxo-
1,2-dihydropyridine-3-carbonitrile (8c). This compound was
obtained as yellowish crystals; yield: 0.255 g (76%); mp: 250-
252˚C (dec.); ir (KBr): ꢀ 3200 (NH), 3090 (arom. CH), 2200
1
(CN), 2150 (N3), 1670 (CO), 1645 (CO) cm-1; H nmr (DMSO-
d6): ꢀ 2.69 (s, 3H, CH3), 3.44 (s, 3H, CH3), 7.51-7.58 (m,
3Harom), 7.91 (d, 2Harom, J = 8 Hz), 8.68 (s, 1H, CH), 11.93 (s,
1H, NH). Anal. Calcd. for C16H13N7O2 (335.30): C, 57.31; H,
3.91; N, 29.24. Found: C, 57.26; H, 3.78; N, 29.34.
6-Azido-1,4-dimethyl-5-phenylhydrazonomethyl-2-oxo-
1,2-dihydropyridine-3-carbonitrile (8d). This compound was
obtained as yellow crystals, yield: 0.265 g (86%); mp: 190-
192˚C (dec.); ir (KBr): ꢀ 3290 (NH), 2220 (CN), 2150 (N3),
1
1635 (CO) cm-1; H nmr (DMSO-d6): ꢀ 2.60 (s, 3H, CH3), 3.44
(s, 3H, CH3), 6.63-7.98 (m, 5Harom), 8.29 (s, 1H, CH), 10.01 (s,
1H, NH); ms: m/z 281 (M+2 –N2, 34), 267 (19), 190 (52), 119
(17), 106 (15), 105 (36), 93 (100), 92(56), 77 (63). Anal. Calcd.
for C15H13N7O (307.29): C, 58.63; H, 4.26; N, 31.90. Found: C,
58.48; H, 4.39; N, 31.81.
6-Cyclohexylamino-5-formyl-1,4-dimethyl-2-oxo-1,2-di-
hydropyridine-3-carbonitrile (15d). This compound was
obtained as colorless crystals, yield: 0.180 g (66%); mp: 210-
212˚C; ir (KBr): ꢀ 3400 (NH), 2950, 2850 (aliph. CH), 2200
6-Amino-1,4-dimethyl-5-phenylhydrazonomethyl-2-oxo-
1,2-dihydropyridine-3-carbonitrile (10). Route (A):
A
mixture of 1 (0.217 g, 1 mmol) and 7d (0.94 g, 1 mmol) was
heated at 140-160˚C for 10 min. After cooling to room
temperature, the resulting solid product was collected by
filtration, washed with EtOH, dried and recrystallized from
EtOH to afford 10.
1
(CN), 1680 (CO), 1640 (CO) cm-1; H nmr (CDCl3): ꢀ 1.25-2.01
(m, 11Haliph), 2.44 (s, 3H, CH3), 3.32 (s, 3H, CH3), 7.82 (d, 1H, J =
13 Hz, NH,), 11.48 (s, 1H, CHO); ms: m/z 274 (M+1, 47), 273 (M+,
47), 230 (21), 191 (41), 190 (9), 175 (2), 160 (2), 146 (3), 120 (3),
97 (63), 83 (19), 55 (100). Anal. Calcd. for C15H19N3O2 (273.32):
C, 65.91; H, 7.01; N, 15.37. Found: C, 65.82; H, 6.94; N, 15.48.
Route (B): Sodium dithionite (0.40 g, 2.30 mmol) was added
portionwise to a stirred solution of 8d (0.20 g, 0.65 mmol) in

Jan-Feb 2008
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Guzman, M. C.; Meador, J. W. III; Ferre, R. A.; Worland, S. T. J. Med.
Chem. 2002, 45, 1607.
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