Synthesis of the novel pyrimido[1,6-a]pyrimidine and imidazo[1,2-c] pyrimidine derivatives based on heterocyclic ketene aminals

Article abstract of DOI:10.1016/j.tet.2011.10.035

A concise and efficient route for the synthesis of pyrimido[1,6-a] pyrimidines and imidazo[1,2-c]pyrimidines by simply refluxing a reaction mixture of different heterocyclic ketene aminals and N,N′-bis(arylmethylidene) arylmethane was developed. This protocol provides an alternative method for application in combinatorial and parallel synthesis in drug discovery.

Full text of DOI:10.1016/j.tet.2011.10.035

Tetrahedron 68 (2012) 319e322
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of the novel pyrimido[1,6-a]pyrimidine and imidazo[1,2-c]pyrimidine
derivatives based on heterocyclic ketene aminals
*
Abdolali Alizadeh , Javad Mokhtari, Mehdi Ahmadi
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 July 2011
Received in revised form 23 September 2011
Accepted 10 October 2011
Available online 18 October 2011
A concise and efficient route for the synthesis of pyrimido[1,6-a]pyrimidines and imidazo[1,2-c]pyrim-
idines by simply refluxing a reaction mixture of different heterocyclic ketene aminals and N,N0-bis(ar-
ylmethylidene)arylmethane was developed. This protocol provides an alternative method for application
in combinatorial and parallel synthesis in drug discovery.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
1,n-Diamines
1,1-Bis(methylthio)-2-nitroethen
N,N0-Bis(arylmethylidene)arylmethane
Pyrimido[1,6-a]pyrimidine
Imidazo[1,2-c]pyrimidine
Multicomponent reaction
1. Introduction
In last few years, combinatorial methods using multicomponent
reactions have been closely examined as a fast and convenient
solution for the synthesis of diverse classes of compounds.1,2 Mul-
ticomponent reactions (MCRs), defined as one-pot reactions in
which at least three functional groups join through covalent bonds,
have been steadily gaining importance in synthetic organic
chemistry.1e4
Heterocyclic ketene aminals (HKAs), because of their distinctive
electronic features, have been significantly used as flexible syn-
thons for the construction of a variety of fused-ring polycyclic
heterocycles and therefore are highly noteworthy in contemporary
organic synthesis.5 These fused heterocyclic structures are fre-
quently found in pharmacophores and play important roles in drug
discovery and are also used as herbicides, pesticides,6 antianxiety
agents,7 antileishmanial agents,8 and antibacterial drugs.9 For ex-
ample, imidazoindoles are present as the key structural motif in the
core structures of novel marine natural products and biologically
active molecules, including the potent cholecystokinin antagonist
asperlicin (7)10 and the antifungal and moderately cytotoxic fumi-
quinazolines A (8) and B (9)11,12 (Fig. 1).
Fig. 1. Structures of novel marine natural products and biologically active compounds.
N,N0-Bis(arylmethylidene)arylmethanes serve as good pre-
cursors for the synthesis of numerous organic compounds, espe-
cially aza-cyclic compounds.13e17 This easily accessible precursor
can be produced by the reaction of aromatic aldehydes and am-
monia solution.
As part of our continuing effort into the design of new routes for
the preparation of biologically active compounds,18e21 herein, we
describe a simple, one-pot, three-component synthesis of pyrimido
* Corresponding author. Tel.: þ98 21 8800663; fax: þ98 21 88006544; e-mail
addresses: aalizadeh@modares.ac.ir, abdol_alizad@yahoo.com.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.10.035

320
A. Alizadeh et al. / Tetrahedron 68 (2012) 319e322
[1,6-a]pyrimidines and imidazo[1,2-c]pyrimidines from heterocy-
clic ketene aminals. The reaction of N,N0-bis(arylmethylidene)aryl-
methanediamine 1 and different diamines in the presence of 1,1-
bis(methylthio)-2-nitroethylene in anhydrous ethanol under
reflux produces compounds 2e4 in 72e88% yields (Table 2).
Encouraged by this success, we extended this reaction of N,N0-
bis(arylmethylidene)arylmethanediamine 1 and different diamines
in the presence of 1,1-bis(methylthio)-2-nitroethylene. The corre-
sponding products 2e4 were synthesized in high yield (74e85%)
and the results are summarized in Table 2.
The structures of compounds 2e4 were deduced from their el-
emental analysis, IR and high-field 1H and 13C NMR spectra. The
mass spectrum of 2 displayed the molecular ion peak at m/z 376,
which is in agreement with the proposed structure. The IR spec-
trum of this compound showed absorption bands due to the NH,
CH, and NO2 groups at 3372, 3251, and 2924 and 1379 cmꢀ1, re-
spectively. The 1H NMR spectrum of 2 showed two multiplets for
2. Results and discussion
The choice of an appropriate reaction medium is of crucial im-
portance for successful synthesis. Initially, the three-component
reaction of N,N0-bis(arylmethylidene)arylmethanediamine 1 and
different diamines in the presence of 1,1-bis(methylthio)-2-
nitroethylene as a simple model substrate was investigated to es-
tablish the feasibility of the strategy and to optimize the reaction
conditions (Scheme 1).
the CH2 groups (
the CH (
d
¼0.91e1.23 and 1.51e1.68 ppm), two singlets for
d
¼4.77 and 5.46), two multiplets for the CH (
d
¼3.30e3.34
and 4.05e4.07), two singlets for the NH groups (
d
¼2.58 and 8.61),
Ar
NH
Ar
N
NO2
N
H
2
NH2
NH2
Ar
Ar
H
NH2
NH2
Ar
N
Ar
NH
NH2
n
MeS
MeS
NO2
H2N
N
N
Ar
N
N
NO2
Ar
1
Ar
N
H
n
NO2
NH
4
3
Scheme 1. Reaction of heterocyclic ketene aminals with N,N0-bis(arylmethylidene)arylmethane.
Different solvents, such as methanol, ethanol, acetonitrile, tet-
rahydrofuran (THF), and dichloromethane were explored. The re-
sults are summarized in Table 1.
and the aromatic moieties gave rise to multiplets in the aromatic
region of the spectrum (
d
¼7.26e7.40 ppm). The 1H-decoupled 13C
NMR spectrum of 2 showed 18 distinct resonances in agreement
with the suggested structure. This process was successfully applied
to other aldehydes as summarized in Table 2 and Scheme 1. As
shown in Scheme 1 and Table 2, the reaction of various aldehydes
with ammonia followed by reaction with different diamines and
1,1-bis(methylthio)-2-nitroethylene, afforded pyrimido[1,6-a]py-
rimidine and imidazo[1,2-c]pyrimidine 2e4 in good yields.
Although we have not established the mechanism of reaction
experimentally, a possible explanation is proposed in Scheme 2.
Compound 3a could result from the initial addition of the ethyl-
enediamine to 1-bis(methylthio)-2-nitroethylene and subsequent
attack of the resulting reactive compound 5 on the compound 1a to
yield intermediate 6. Cyclization of 6 and subsequent loss of alde-
hyde lead to compound 3a (Scheme 2).
Table 1
Synthetic results of 2 under different reactions conditions
Entry
Solvent
Temp
Time/h
Yielda (%)
1
2
3
4
5
MeOH
EtOH
H3CCN
THF
Reflux
Reflux
Reflux
Reflux
Reflux
12
8
8
10
10
54
74
57
69
21
CH2Cl2
a
Isolated yield.
Table 2
Synthesis of pyrimido[1,6-a]pyrimidine and imidazo[1,2-c]pyrimidine
Product
Ar
n
Time
Yield (%)
3. Conclusion
2
Ph
Ph
d
1
1
2
2
3
3
d
8
8
8
74
80
81
83
75
80
85
79
78
3a
3b
3c
3d
3e
3f
p-MeOC6H4
Ph
p-MeOC6H4
Ph
p-MeOC6H4
Ph
p-MeOC6H4
In summary, a simple and easy method has been developed for
the quick construction of novel pyrimido[1,6-a]pyrimidines and
imidazo[1,2-c]pyrimidines by the reaction of HKAs with N,N0-
bis(arylmethylidene)arylmethanediamine. These types of hetero-
cycles contain a number of functional groups and are therefore
valuable precursors for the diversity orientated synthesis of pyr-
imido[1,6-a]pyrimidine and imidazo[1,2-c]pyrimidine libraries,
which are of potential use in the facile preparation of biologically
active molecules. Further work on the reactions of compound 1 is
under way.
8
10
10
10
10
10
4a
4b
d
As can be seen from Table 1, the best results were obtained by
refluxing the reaction mixture in EtOH to yield product 2 in good
yield (Table 1, entry 2).

A. Alizadeh et al. / Tetrahedron 68 (2012) 319e322
321
NMR (500.13 MHz, CDCl3):
d
¼0.91e1.23 (2H, m, CH2), 1.51e1.68
(6H, m, 3CH2), 2.58 (1H, s, NH), 3.30e3.34 (1H, m, CHeNH),
4.05e4.07 (1H, m, CHeN), 4.77 (1H, s, CH), 5.46 (1H, s, CH),
7.26e7.40 (10H, m, Ar), 8.61 (1H, s, NH). 13C NMR (125.75 MHz,
CDCl3):
d
¼19.71 (CH2), 20.80 (CH2), 25.60 (CH2), 25.79 (CH2), 53.88
(CH), 54.26 (CH), 58.03 (CH), 66.39 (CH), 106.31 (CeNO2), 126.95
(2CH of Ar),127.49 (CH of Ar),127.74 (2CH of Ar),128.52 (2CH of Ar),
129.26 (2CH of Ar), 129.56 (CH of Ar), 136.82 (Cipso), 140.62 (Cipso),
157.57 (C]CNO2). MS (EI, 70 eV): m/z (%)¼376 (1) [Mþ], 330 (8), 272
(100), 225 (32), 194 (8), 169 (12), 128 (13), 104 (25), 91 (1), 77 (16).
4.3.2. 8-Nitro-5,7-diphenyl-1,2,3,5,6,7-hexahydroimidazo[1,2-c]py-
rimidine (3a). White powder, mp¼240 ꢁC (dec), 0.26 g, yield 80%. IR
(KBr): 3281 (NH), 3044 (NH), 2924 (CH), 1592 and 1528 (Ar), 1405
(NO2). Anal. Calcd for C18H18N4O2 (322.36): C, 67.07; H, 5.63; N,
17.38%. Found: C, 67.02; H, 5.57; N, 17.31%. 1H NMR (500.13 MHz,
CDCl3):
(2H, m, CH2eN), 4.74 (1H, s, CH), 5.50 (1H, s, CH), 7.24e7.42 (10H, m,
Ar), 8.74 (1H, s, NH). 13C NMR (125.75 MHz, CDCl3):
47.13 (CH2), 54.18 (CH), 68.90 (CH), 106.18 (CeNO2), 126.97 (2CH of
Ar), 127.53 (CH of Ar), 127.71 (2CH of Ar), 128.52 (2CH of Ar), 129.31
(2CH of Ar), 129.65 (CH of Ar), 136.68 (Cipso), 140.39 (Cipso), 157.86
(C]CNO2). MS (EI, 70 eV): m/z (%)¼322 (2) [Mþ], 276 (13), 218
(100), 194 (6), 171 (32), 143 (4), 115 (13), 104 (25), 89 (8), 77 (16).
d
¼2.72 (1H, br, NH), 3.21e3.32 (2H, m, CH2eNH), 3.69e3.80
d¼42.34 (CH2),
Scheme 2. Proposed mechanism.
4. Experimental
4.1. General
All reactions were carried out in oven-dried glassware. Progress
of reactions was monitored by thin layer chromatography while
purification was effected by column chromatography, using silica
gel (Merck 230e240 mesh). Diamines, aldehydes, and ammonia
were obtained from Merck (Germany) and Fluka (Switzerland) and
were used without further purification. Melting points were mea-
sured on an Electrothermal 9100 apparatus. Elemental analyses for
C, H, and N were performed using a Heraeus CHNeO-Rapid ana-
lyzer. Mass spectra were recorded on a FINNIGAN-MATT 8430 mass
spectrometer operating at an ionization potential of 70 eV. 1H and
13C NMR spectra were measured (DMSO-d6) with a Bruker DRX-500
AVANCE spectrometer at 500.13 and 125.8 MHz, respectively. IR
spectra were recorded on a Shimadzu IR-460 spectrometer, absor-
4.3.3. 4-[5-(4-Methoxyphenyl)-8-nitro-1,2,3,5,6,7-hexahydroimidazo
[1,2-c]pyrimidine-7-yl]phenyl methyl ether (3b). White powder,
mp¼204 ꢁC (dec), 0.31 g, yield 81%. IR (KBr) (nmax, cmꢀ1): 3364
(NH), 3267 (NH), 2861 (CH), 1594 and 1514 (Ar), 1379 (NO2). Anal.
Calcd for C20H22N4O4 (382.41): C, 62.82; H, 5.80; N, 14.65%. Found:
C, 62.79; H, 5.76; N, 14.60%. 1H NMR (500.13 MHz, CDCl3): dH¼2.83
(1H, s, NH), 3.19e3.25 (2H, m, CH2eNH), 3.67e3.72 (2H, m, CH2N),
3.78 (6H, s, OCH3), 4.70 (1H, s, CH), 5.40 (1H, s, CH), 6.85e6.90 (4H,
m, 4CH of Ar), 7.26e7.29 (4H, m, 4CH of Ar), 8.71 (1H, s, NH). 13
C
NMR (125.75 MHz, CDCl3): dC¼42.38 (CH2), 47.11 (CH2), 53.71 (CH),
55.30 (OCH3), 55.36 (OCH3), 68.34 (CH), 106.49 (CeNO2), 113.90
(2CH of Ar), 114.56 (2CH of Ar), 128.36 (2CH of Ar), 128.84 (2CH of
Ar), 132.55 (2Cipso), 157.73 (C]CNO2), 158.99 (CipsoeOMe), 160.41
(CipsoeOMe) ppm. MS (EI, 70 eV): m/z (%)¼383 (1) [Mþþ1], 246
(50), 200 (16), 134 (100), 119 (25), 108 (13), 91 (25), 77 (30), 65 (32).
bances are reported in cmꢀ1
.
4.2. General procedure for the preparation of compounds 1
4.3.4. 9-Nitro-6,8-diphenyl-1,3,4,6,7,8-hexahydro-2H-pyrimido[1,6-
a]pyrimidine (3c). White powder, mp¼220 ꢁC (dec), 0.28 g, yield
83%. IR (KBr): 3253 (NH), 3037 (NH), 2899 (CH), 1568 (Ar), 1378
(NO2). Anal. Calcd for C19H20N4O2 (336.39): C, 67.84; H, 5.99; N,
16.66%. Found: C, 67.79; H, 5.92; N, 16.61%. 1H NMR (500.13 MHz,
The benzaldehyde (for 1a) or 4-methoxybenzaldehyde (for 1b)
(3 mmol) was added to NH4OH (30%, 10 mL) and the solution was
stirred for 5 h at reflux. During this time, a white precipitate
formed. The precipitate was removed by filtration and dried.
CDCl3):
d
¼1.79e1.95 (2H, m, CH2), 2.80e2.88 (2H, m, CH2), 2.99
3 3 3
4.3. General procedure for the preparation of compounds
2e4, exemplified on 2
(1H, dd, JHH¼11.8 Hz, JHH¼3.5 Hz, NH), 3.38 (1H, t, JHH¼9.0 Hz,
2 3
CH2), 3.52 (1H, dd, JHH¼13.0 Hz, JHH¼4.6 Hz, CH2), 4.79 (1H, d,
3JHH¼11.8 Hz, CH), 5.61 (1H, d, 3JHH¼3.5 Hz, CH), 7.27e7.38 (10H, m,
A mixture of cyclohexane-1,2-diamine (0.11 g, mmol), 1,1-
bis(methylthio)-2-nitroethylene (0.16 g, 1 mmol) in a 50 mL flask
was stirred at reflux for 12 h, then N,N0-bis(phenylmethylidene)
phenylmethanediamine 1a (0.3 g, 1 mmol) was added and the re-
action mixture heated at reflux for the time period as indicated in
Table 1. When the reaction mixture was cooled to room tempera-
ture, a white solid precipitated. The precipitates were filtered and
washed with diethyl ether to give product 2 in 74% yields. All
products gave satisfactory spectral data in accordance with the
assigned structures.
Ar), 11.74 (1H, s, NH). 13C NMR (125.75 MHz, CDCl3):
d¼20.26 (CH2),
38.20 (CH2), 43.67 (CH2), 53.86 (CH), 73.01 (CH), 107.79 (CeNO2),
127.09 (2CH of Ar), 127.37 (CH of Ar), 127.53 (2CH of Ar), 128.52
(2CH of Ar), 129.27 (2CH of Ar), 129.34 (CH of Ar), 137.29 (Cipso),
139.26 (Cipso), 153.47 (C]CNO2). MS (EI, 70 eV): m/z (%)¼336 (1)
[Mþ], 313 (2), 236 (20), 149 (15), 137 (25), 111 (27), 97 (58), 81 (100),
69 (90), 57 (76).
4.3.5. 4-[6-(4-Methoxyphenyl)-9-nitro-1,3,4,6,7,8-hexahydro-2H-
pyrimido[1,6-a]pyrimidine-8-yl]phenyl methyl ether (3d). White
powder, mp¼165 ꢁC (dec), 0.3 g, yield 75%. IR (KBr): 3244 (NH),
2935 (CH), 1580 (Ar), 1380 (NO2). Anal. Calcd for C21H24N4O4
(396.44): C, 63.62; H, 6.10; N, 14.13%. Found: C, 63.57; H, 6.07; N,
4.3.1. 4-Nitro-1,3-diphenyl-1,2,3,5,5a,6,7,8,9,9a-decahydropyrimido
[1,6-a][1,3]benzimidazole (2). White powder, mp¼245 ꢁC (dec),
0.28 g, yield 74%. IR (KBr): 3372 (NH), 3251 (NH), 2924 (CH), 1587
and 1494 (Ar), 1379 (NO2). Anal. Calcd for C22H24N4O2 (376.45): C,
70.19; H, 6.43; N, 14.88%. Found: C, 70.12; H, 6.36; N, 14.81%. 1H
14.08%. 1H NMR (500.13 MHz, CDCl3):
d¼1.90e1.96 (2H, m, CH2),
2.84e2.87 (2H, m, CH2), 3.04 (1H, br, NH), 3.37e3.56 (2H, m, CH2),
3.81 (s, 2OCH3), 4.77 (1H, s, CH), 5.56 (1H, s, CH), 6.90e7.27 (8H, m,

322
A. Alizadeh et al. / Tetrahedron 68 (2012) 319e322
Ar), 11.71 (1H, s, NH). 13C NMR (125.75 MHz, CDCl3):
d¼20.40 (CH2),
(C]CNO2). MS (EI, 70 eV): m/z (%)¼364 (1) [Mþ], 318 (58), 260
38.32 (CH2), 43.65 (CH2), 53.31 (CH), 55.30 (OCH3), 55.40 (OCH3),
72.47 (CH), 107.98 (CeNO2), 114.04 (2CH of Ar), 114.73 (2CH of Ar),
128.22 (2CH of Ar), 128.65 (2CH of Ar), 129.31 (Cipso), 131.18 (Cipso),
153.50 (C]CNO2), 159.06 (CipsoeOCH3), 160.41 (CipsoeOCH3),. MS
(EI, 70 eV): m/z (%)¼396 (1) [Mþ], 272 (1), 260 (1), 167 (8), 149 (25),
135 (100), 107 (16), 84 (58), 71 (32), 57 (51).
(100), 213 (49), 194 (24), 138 (31), 104 (58), 91 (25), 77 (51).
4.3.9. 4-[6-(4-Methoxyphenyl)-3,3-dimethyl-9-nitro-1,3,4,6,7,8-
hexahydro-2H-pyrimido[1,6-a]pyrimidine-8-yl]phenyl methyl ether
(4b). White powder, mp¼210 ꢁC (dec), 0.33 g, yield 78%. IR (KBr)
(
nmax, cmꢀ1): 3285 (NH), 2942 (CH), 1582 (Ar), 1389 (NO2). Anal.
Calcd for C23H28N4O4 (424.49): C, 65.08; H, 6.65; N, 13.2%. Found:
4.3.6. 10-Nitro-7,9-diphenyl-1,2,3,4,5,7,8,9-octahydropyrimido[1,6-
a][1,3]diazepine (3e). White powder, mp¼212 ꢁC (dec), 0.28 g, yield
80%. White powder. IR (KBr): 3240 (NH), 2926 (CH), 1576 (Ar), 1379
(NO2). Anal. Calcd for C20H22N4O2 (350.42): C, 68.55; H, 6.33; N,
15.99%. Found: C, 68.51; H, 6.27; N, 15.93%. 1H NMR (500.13 MHz,
C, 65.01; H, 6.59;N,13.1%.1HNMR(500.13 MHz, CDCl3): dH¼0.91 (6H,
3
3
s, CH3), 2.33 (1H, d, JHH¼12.2 Hz, CH2), 2.56 (1H, d, JHH¼12.6 Hz,
CH2), 2.96 (1H, s, NH), 3.09 (2H, m, CH2), 3.78 (6H, s, CH3), 4.70 (1H, s,
CH), 5.55 (1H, s, CH), 6.87e6.90 (4H, m, 4CH of Ar), 7.27 (4H, m, 4CH
of Ar), 11.75 (1H, s, NH). 13C NMR (125.75 MHz, CDCl3): dC¼23.60
(CH3), 24.85 (CH3), 27.36 (C(CH3)2), 49.66 (CH2), 53.38 (CH2), 55.28
(OCH3), 55.35 (OCH3), 55.56 (CH), 72.82 (CH),107.86 (CeNO2),113.82
(2CH of Ar), 114.60 (2CH of Ar), 128.64 (4CH of Ar), 129.23 (Cipso),
131.29 (Cipso), 152.58 (C]CNO2), 159.00 (CipsoeOMe), 160.31
(CipsoeOMe) ppm. MS (EI, 70 eV): m/z (%)¼424 (1) [Mþ], 288 (1), 217
(30), 203 (8), 150 (60), 134 (100), 112 (20), 91 (16), 77 (14), 57 (25).
CDCl3):
d
¼1.18e1.19 (1H, m, CH2), 1.56e1.57 (2H, m, CH2), 1.84e1.86
(1H, m, CH2), 2.95e3.01 (2H, m, CH2), 3.06 (1H, br, NH), 3.39e3.44
3
(1H, m, CH2), 3.66e3.68 (1H, m, CH2), 4.67 (1H, d, JHH¼12.2 Hz,
CH), 5.67 (1H, s, CH), 7.26e7.45 (10H, m, Ar), 11.58 (1H, s, NH). 13
C
NMR (125.75 MHz, CDCl3):
d
¼25.77 (CH2), 26.19 (CH2), 45.75 (CH2),
51.65 (CH2), 54.03 (CH), 75.62 (CH), 112.26 (CeNO2), 127.23 (2CH of
Ar), 127.51 (CH of Ar), 127.73 (2CH of Ar), 128.65 (2CH of Ar), 129.06
(2CH of Ar), 129.25 (CH of Ar), 138.41 (Cipso), 138.89 (Cipso), 162.16
(C]CNO2). MS (EI, 70 eV): m/z (%)¼350 (1) [Mþ], 304 (16), 246
(100), 199 (54), 160 (8), 140 (10), 104 (50), 91 (13), 77 (32).
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2011.10.035.
4.3.7. 4-[7-(4-Methoxyphenyl)-10-nitro-1,2,3,4,5,7,8,9-
octahydropyrimido[1,6-a][1,3]diazepin-9-yl]phenyl methyl ether
(3f). White powder, mp¼208 ꢁC (dec), 0.35 g, yield 85%. Anal. Calcd
for C22H26N4O4 (410.47): C, 64.38; H, 6.38; N, 13.65%. Found: C,
64.30; H, 6.31; N, 13.62%. IR (KBr) (nmax, cmꢀ1): 3254 (NH), 2934
(CH), 1576 (Ar), 1390 (NO2). 1H NMR (500.13 MHz, CDCl3):
dH¼1.17e1.85 (4H, m, CH2), 2.94e3.01 (2H, m, CH2), 3.05(1H, br,
NH), 3.36e3.41(1H, m, CH2), 3.65 (1H, m, CH), 3.80 (6H, s, OCH3),
4.62 (1H, s, CH), 5.58 (1H, s, CH), 6.87e6.90 (4H, m, 4CH of Ar),
7.26e7.37 (4H, m, 4CH of Ar), 11.55 (1H, s, NH). 13C NMR
(125.75 MHz, CDCl3): dC¼25.81 (CH2), 26.19 (CH2), 45.74 (CH2),
51.53 (CH2), 53.46 (CH), 55.29 (OCH3), 55.33 (OCH3), 75.08 (CH),
112.44 (CeNO2), 114.05 (2CH of Ar), 114.37 (2CH of Ar), 128.51 (2CH
of Ar), 128.81 (2CH of Ar), 130.49 (Cipso), 130.87 (Cipso), 159.05 (C]
CNO2), 160.19 (CipsoeOMe),162.08 (CipsoeOMe) ppm. MS (EI, 70 eV):
m/z (%)¼411 [Mþþ1], 274 (80), 229 (58), 189 (35), 157 (65), 135
(100), 119 (69), 97 (41), 84 (25), 55 (51).
References and notes
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4.3.8. 3,3-Dimethyl-9-nitro-6,8-diphenyl-1,3,4,6,7,8-hexahydro-2H-
pyrimido[1,6-a]pyrimidine (4a). White powder, mp¼205 ꢁC (dec),
0.29 g, yield 79%. IR (KBr): 3257 (NH), 3038 (NH), 2955 (CH), 1586
and 1557 (Ar), 1387 (NO2). Anal. Calcd for C21H24N4O2 (364.44): C,
69.21; H, 6.64; N, 15.37%. Found: C, 69.16; H, 6.57; N, 15.32%. 1H
NMR (500.13 MHz, CDCl3):
d
¼0.91 (3H, s, CH3), 0.92 (3H, s, CH3),
3
3
2.33 (1H, d, JHH¼12.9 Hz, CH2), 2.57 (1H, d, JHH¼13.0 Hz, CH2),
3.06e3.10 (2H, m, CH2), 3.15 (1H, br, NH), 4.73 (1H, s, CH), 5.6 (1H, s,
CH), 7.26e7.3 (10H, m, Ar), 11.78 (1H, s, NH). 13C NMR (125.75 MHz,
CDCl3):
d
¼23.57 (CH3), 24.83 (CH3), 27.39 (C(CH3)2), 49.66 (CH2),
53.95 (CH2), 55.66 (CH), 73.41 (CH), 107.63 (CeNO2), 127.41 (2CH of
Ar), 127.43 (CH of Ar), 127.57 (2CH of Ar), 128.44 (2CH of Ar), 128.57
(2CH of Ar), 129.27 (CH of Ar), 137.22 (Cipso), 139.37 (Cipso), 152.68