Synthesis of symmetrical and unsymmetrical bis(pyrrolo[2,3-d]pyrimidinyl)methanes

Article abstract of DOI:10.1039/c4ra09729g

Some novel symmetrical bis(pyrrolo[2,3-d]pyrimidinyl)methanes were synthesized via diheteroarylation of sp³ CH bond of acetophenones with molecular iodine and DMSO. Further, an efficient reaction protocol was developed with which both symmetrical and some novel unsymmetrical bis(pyrrolo[2,3-d]pyrimidinyl)methanes were synthesized. For this purpose, we have exploited the highly reactive and good leaving nature of 1,3-dimethylbarbituric acid.

Full text of DOI:10.1039/c4ra09729g

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Synthesis of symmetrical and unsymmetrical
bis(pyrrolo[2,3-d]pyrimidinyl)methanes†
Cite this: RSC Adv., 2014, 4, 60640
*
Meenakshi Sharma and Pulak J. Bhuyan
Some novel symmetrical bis(pyrrolo[2,3-d]pyrimidinyl)methanes were synthesized via diheteroarylation of
sp3 CH bond of acetophenones with molecular iodine and DMSO. Further, an efficient reaction protocol
was developed with which both symmetrical and some novel unsymmetrical bis(pyrrolo[2,3-d]
pyrimidinyl)methanes were synthesized. For this purpose, we have exploited the highly reactive and good
leaving nature of 1,3-dimethylbarbituric acid.
Received 3rd September 2014
Accepted 31st October 2014
DOI: 10.1039/c4ra09729g
www.rsc.org/advances
reaction of pyrrolo[2,3-d]pyrimidines and aldehydes/ketones via
a mild process of carbon–carbon bond formation using iodine
as catalyst in aqueous medium.20 In the present paper, we report
Introduction
The importance of pyrrolo[2,3-d]pyrimidines is well recognized
by biological, medicinal and synthetic organic chemists.
Compounds with this molecular motif possess diverse biological
activities such as anti-microbial,1 analgesic,2 anti-inammatory,3
anti-viral,4 anti-cancer,5 antioxidant and neuroprotective activity.6
Some of their representatives are protein kinase inhibitors,7 E1
enzyme inhibitors,8 insulin-like growth factor 1 receptor inhibi-
tors,9 STAT6 inhibitors10 and 2 microtubule targeting agents.11
Pyrrolo[2,3-d]pyrimidine constitutes the basic molecular unit of
various nucleosides12 such as toyocamycine, tubercidin and
sangivamycin which exhibit antiviral, antimicrobial, antiparasitic
and antineoplastic activity. Some other compounds of this class
have signicant activity against a variety of RNA, DNA viruses,
HSV-1, HSV-2 and HCMV.13
the full account of our advanced study of the reaction process
and synthesis of some novel bis(pyrrolo[2,3-d]pyrimidinyl)
methane derivatives 3 from the reaction of pyrrolo[2,3-d]-
pyrimidine-2,4-diones 1 and acetophenones 2 via diheteroar-
ylation of sp3 CH bond in the presence of molecular iodine and
DMSO (Scheme 1), and also an efficient method for the
synthesis of both symmetrical and novel unsymmetrical-bis-
(pyrrolo[2,3-d]pyrimidinyl)methanes (Scheme 3).
Results and discussion
We initiated our study with an objective to synthesize some new
bis(pyrrolo[2,3-d]pyrimidinyl)methane derivatives via dihetero-
arylation of sp3 CH bond of acetophenones with pyrrolo[2,3-d]
pyrimidine-2,4-diones using SeO2 + BF3$Et2O system in dry
toluene.17 In the reaction strategy, we treated 1,3-dimethyl-pyr-
rolo[2,3-d]pyrimidine-2,4-dione 1a and acetophenone 2a in the
presence of SeO2 + BF3$Et2O system in dry toluene, initially at
room temperature and then in reuxing conditions. But no
satisfactory results were obtained. It was observed that the
Insertion of an aryl group to a sp3 carbon atom next to a
carbonyl group, which frequently involves in the synthesis of
many useful compounds including medicines, natural products
of biological signicance and industrial materials,14 is a long-
standing problem in synthetic organic chemistry.15 Most
common and widely used methods for a-arylation of sp3 C–H
bond of ketones include the coupling of C sp3–H bond with aryl
halide/aryl metal and cross-dehydrogenative coupling.16 Very
recently, Myrboh and his co-workers reported the sp3 C–H bond
diarylation by selenium dioxide in presence of BF3$Et2O.17
As a part of our continued interest in the synthesis of diverse
heterocyclic compounds,18 particularly annelated pyrimidines
of biological importance,19 in a recent communication, we
reported for the rst time the synthesis of bis(pyrrolo[2,3-d]
pyrimidinyl)methanes, a novel class of compounds, from the
Medicinal Chemistry Division, CSIR-North East Institute of Science & Technology,
Jorhat 785006, Assam, India. E-mail: pulak_jyoti@yahoo.com; Fax: +91-376-
2370011; Tel: +91-376-2370121
† Electronic supplementary information (ESI) available: Compound
characterizations data (1H NMR, 13C NMR spectra and elemental analysis). See
DOI: 10.1039/c4ra09729g
Scheme 1 Synthesis of bis(pyrrolo[2,3-d]pyrimidinyl)methanes 3.
60640 | RSC Adv., 2014, 4, 60640–60647
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solubility of 1,3-dimethylpyrrolo[2,3-d]pyrimidine-2,4-dione 1a dione 1a was more reactive (entry 1–8, Table 1) than 3-methyl-
is very poor in toluene, and at elevated temperature some pyrrolo[2,3-d]pyrimidine-2,4-dione 1b (entry 9–16, Table 1) and
breakdown products were formed instead of the desired gave better yield of the products.
compound. Then, we replaced (SeO2 + BF3$Et2O) system with
The probable mechanism of the reaction is outlined in the
(DMSO + I2)21 system which is considerably mild and easy to Scheme 2. The reaction occurred via initial iodination of the
handle, and DMSO also acts as solvent. So, rst we conducted acetophenone 2a by iodine to give the compound [A] which was
the reaction using 1,3-dimethylpyrrolo[2,3-d]pyrimidine-2,4- subsequently oxidized by DMSO to the intermediate aldehyde
dione 1a and acetophenone 2a in the presence of DMSO + I2 [B].21 The rest of the reaction follow the mechanism as reported
at room temperature using DMSO as solvent. But the reaction in the previous paper.20 The aldehyde [B] suffered a nucleophilic
did not occur. Then the reaction was studied under reuxing attack by the pyrrolo[2,3-d]pyrimidines 1a in presence of iodine
condition. The reaction occurred to give the desired product, to give the intermediate [C] by the elimination of water mole-
but a number of breakdown products were formed. However, cule. The intermediate [C] then suffered a nucleophilic attack by
the formation of the desired product was improved when the the second 1,3-dimethylpyrrolo[2,3-d]pyrimidine-2,4-dione 1a
reaction was carried out at 90 ꢀC. But very interestingly, when we molecule to give the nal product 3a. The mechanism was
rst carried out the reaction using acetophenone 2a with DMSO further established by performing the reaction of commercially
ꢀ
+ I2 at 90 C, and resulting solution was treated with 1,3-dime- available phenyl glyoxal [B] with 1,3-dimethylpyrrolo[2,3-d]
thylpyrrolo[2,3-d]pyrimidine-2,4-dione 1a at room temperature pyrimidine-2,4-dione 1a in the presence of iodine as catalyst
under stirring condition, afforded the desired product bis- using DMSO as solvent which afforded the expected compound
(pyrrolo[2,3-d]pyrimidinyl)methanes 3a in almost pure form 3a in good yield.
and in high yield. The structure of the compound was ascer-
It was observed in our previous20 and the present study that
tained as 3a from the spectroscopic data and elemental anal- the intermediate [C] (in the present case) is not isolable which
ysis. The 1H NMR spectra (DMSO-d6) of the compound showed suffers a quick nucleophilic attack by the second molecule of
the presence of an isolated proton at d 6.36 as singlet, and two pyrrolo[2,3-d]pyrimidine-2,4-dione giving symmetrical bis-
symmetric protons of the two pyrrolo[2,3-d]pyrimidine-2,4- (pyrrolo[2,3-d]pyrimidinyl)methanes in all the cases. Therefore,
dione molecular units at d 6.03 as singlet. A clean peak of the we have efficiently developed the reaction process which was
two symmetric >NH protons were observed at d 11.77 as a applicable for the synthesis of both symmetrical and unsym-
singlet. The mass spectra showed a sharp molecular ion peak at metrical bis(pyrrolo[2,3-d]pyrimidinyl)methanes that contain
475.6 ([M + H]+). The generality of the reaction was established two similar or dissimilar pyrrolo[2,3-d]pyrimidine-2,4-dione
by synthesizing compounds 3a–p and characterizing them molecules respectively (Scheme 3). For this purpose, we have
(Table 1). It was observed that acetophenones 2 with both exploited the highly reactive and good leaving nature of 1,3-
electron donating and electron withdrawing groups at the dimethylbarbituric acid which we demonstrated in our earlier
aromatic ring are equally reactive and gave good yield of the works.19d,22 In the reaction protocol, 1,3-dimethylbarbituric acid
products. However, 1,3-dimethylpyrrolo[2,3-d]pyrimidine-2,4- 4 was rst reacted with aldehydes 5 following our reported
method23 to afford the Knoevenagel condensed products 6
Table 1 Synthesis of bis(pyrrolo[2,3-d]pyrimidinyl)methanes 3a
En.
R1
Pd.
R.T. (h)
Yield (%)
1
2
3
4
5
6
7
8
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
H
H
H
H
C6H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
82
80
80
82
81
81
79
82
78
77
77
78
78
78
75
78
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
4-BrC6H4
4-NO2C6H4
2-Thiophenyl
2-Naphthyl
C6H5
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
9
10
11
12
13
14
15
16
4-BrC6H4
H
H
H
4-NO2C6H4
2-Thiophenyl
2-Naphthyl
a
En. ¼ entry; Pd. ¼ product; R.T. ¼ reaction time.
Scheme 2 Plausible mechanism for the formation of 3a.
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analysis and by comparing with the authentic samples we
prepared earlier.20 On the other hand, utilization of compounds
8, dissimilar from compounds 1 produced unsymmetrical
bis(pyrrolo[2,3-d]pyrimidinyl)methanes (entry 3–17). The struc-
ture of the novel unsymmetrical bis(pyrrolo[2,3-d]pyrimidinyl)
methanes (entry 3–17, Table 2) were conrmed from their
spectroscopic data and elemental analysis.
As in the earlier case, both electron donating and electron
withdrawing groups at the aromatic ring of aldehydes 5 are
equally reactive and gave good yield of the products. Again, N-
methylated pyrrolo[2,3-d]pyrimidine-2,4-diones were more
reactive than the partially unsubstituted pyrrolo[2,3-d]
pyrimidine-2,4-diones. However, although the condensation of
glyoxal [B] and 1,3-dimethylbarbituric acid 4 took place very
easily,24 the Michael addition of pyrrolo[2,3-d]pyrimidine-2,4-
diones 1 to the condensed product did not occur under our
reaction conditions (Scheme 4). It might be because of the keto
group which deactivates the nucleophilic addition.
The mechanism for the formation of the 9 is outlined in the
Scheme 5. Michael addition of compound 1 to the Knoevenagel
condensed product 6 produced the compound 7. Then, the
intermediate [X], formed in situ from compound 7 under
thermal condition via elimination of compound 4, suffered
nucleophilic attack by the compound 8 in presence of iodine to
give the product 9. The mechanism was supported by the
Scheme 3 Synthesis of bis(pyrrolo[2,3-d]pyrimidinyl)methanes 9.
which on stirring with pyrrolo[2,3-d]pyrimidine derivatives 1 at
room temperature afforded the compounds 7 (Scheme 3). The
compound 7, on treatment with various pyrrolo[2,3-d]
pyrimidine-2,4-diones 8 in presence of iodine as catalyst
under reuxing conditions in acetonitrile afforded bis(pyrrolo
[2,3-d]pyrimidinyl)methanes 9 in very high yields (Table 2). 1,3-
Dimethylbarbituric acid 4 was eliminated in the reaction
process which was isolated and recycled in the reaction process.
The use of compounds 8, identical with compounds 1 (Scheme
1) produced symmetrical bis(pyrrolo[2,3-d]pyrimidinyl)meth-
anes (entry 1 and 2, Table 2). The structure of the compounds
were ascertained from the spectroscopic data, elemental
Table 2 Synthesis of bis(pyrrolo[2,3-d]pyrimidinyl)methanes 9a
Scheme 4
En.
R1
R3
R4
R5
Pd.
R.T. (h)
Yd. (%)
1
2
3
4
5
6
7
8
CH3
H
Ph
Ph
Ph
H
H
H
H
CH3
H
H
H
H
CH3
CH3
CH3
CH3
CH3
CH3
H
9a
9b
9c
9d
9e
9f
9g
9h
9i
9j
9k
9l
9m
9n
9o
9p
9q
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
95
92
84
82
80
90
89
87
70
69
68
83
82
85
84
70
68
CH3
CH3
CH3
CH3
CH3
CH3
H
4-OCH3C6H4
4-NO2C6H4
Ph
4-OCH3C6H4
4-NO2C6H4
Ph
4-OCH3C6H4
4-NO2C6H4
Thiophenyl
(CH3)2CH
Thiophenyl
(CH3)2CH
Thiophenyl
(CH3)2CH
H
CH3
CH3
CH3
CH3
CH3
CH3
H
9
10
11
12
13
14
15
16
17
H
H
CH3
CH3
CH3
CH3
H
H
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
a
Scheme 5 Mechanism for the formation of bis(pyrrolo[2,3-d]pyr-
imidinyl)methanes 9.
En ¼ entry; Pd. ¼ product; R.T. ¼ reaction time; Yd ¼ yield.
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isolation and characterization of the eliminated 1,3-dime- (2C), 104.1 (2C), 126.9 (2C), 129.0 (2C), 129.3 (2C), 133.9, 135.9,
thylbarbituric acid 4 from the reaction mixture. Notably, such 139.7 (2C), 151.1 (2C), 158.6 (2C), 194.4; IR (KBr) nmax 3570.2,
good leaving nature of the compound 4 is well documented.19d,22 3204.8, 1694.9, 1558.9 cmꢂ1; MS (ESI) 475.6 ([M + H]+); anal. cald
for C24H22N6O5 C, 60.75; H, 4.67; N, 17.71% found: C, 60.80; H,
4.71; N, 17.75%.
Conclusions
1
ꢀ
3b. Purple solid. Yield: 394 mg (80%); mp. 276–280 C; H
NMR (DMSO-d6, 300 MHz) d (ppm) 2.35 (s, 3H), 3.18 (s, 6H), 3.42
(s, 6H), 6.03 (s, 2H), 6.13 (s, 1H), 7.32 (d, J ¼ 7.92 Hz, 2H), 7.91
(d, J ¼ 7.98 Hz, 2H), 11.75 (s, 2H, NH); 13C NMR (DMSO-d6, 75
MHz) d (ppm) 21.5, 28.0 (2C), 31.0 (2C), 45.7, 98.7 (2C), 104.1
(2C), 127.0 (2C), 129.1 (2C), 129.8 (2C), 133.4, 139.7 (2C), 144.4,
151.1 (2C), 158.6 (2C), 194.0; IR (KBr) nmax 3374.5, 3277.5,
1686.2, 1555.6 cmꢂ1; MS (ESI) 489.3 ([M + H]+); anal. cald for
In conclusion, we have reported the synthesis of some novel
bis(pyrrolo[2,3-d]pyrimidinyl)methanes 3, via diheteroarylation
of sp3 CH bond of acetophenones in the presence of molecular
iodine and DMSO. The reactants were consumed completely in
the reaction process and single product was isolated in each
case. The very small amount of impurity observed in the TLC
study, was removed by column chromatography. Thus, products
were obtained in very high yield. Furthermore, we have devel-
oped the reaction protocol in an efficient way which produced
both symmetrical and unsymmetrical bis(pyrrolo[2,3-d]pyr-
imidinyl)methanes as per requirements. The products were
obtained in solid form aer simple work up procedure and were
puried by crystallization.
C
25H24N6O5 C, 61.47; H, 4.95; N, 17.20% found: C, 61.49; H,
4.97; N, 17.26%.
3c. Pink solid. Yield: 403 mg (80%); mp. 275–277 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d (ppm) 3.18 (s, 6H), 3.42 (s, 6H), 3.66 (s,
3H), 6.02 (s, 2H), 6.15 (s, 1H), 7.31 (d, J ¼ 10.38 Hz, 2H), 7.90 (d, J
¼ 10.95 Hz, 2H), 11.76 (s, 2H, NH); 13C NMR (DMSO-d6, 75 MHz)
d (ppm) 28.0 (2C), 31.0 (2C), 42.3, 56.0, 98.4 (2C), 102.9 (2C),
114.2 (2C), 128.5, 129.7 (2C), 132.5 (2C), 132.9, 139.6 (2C), 151.1
(2C), 158.7 (2C), 194.0; IR (KBr) nmax 3375.5, 3278.5, 1687.2,
1554.6 cmꢂ1; MS (ESI) 505.3 ([M + H]+); anal. cald for
Experimental
General considerations
C
25H24N6O6 C, 59.52; H, 4.80; N, 16.66% found: C, 59.57; H,
Melting points were measured with a Buchi-540 melting point
apparatus. IR spectra were recorded on a SHIMADZU FTIR-
4.87; N, 16.69%.
3d. Pink solid. Yield: 416 mg (82%); mp. 274–279 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d (ppm) 3.18 (s, 6H), 3.42 (s, 6H), 6.04 (s,
2H), 6.14 (s, 1H), 7.61 (d, J ¼ 8.46 Hz, 2H), 8.01 (d, J ¼ 8.49 Hz,
2H), 11.74 (s, 2H, NH); 13C NMR (DMSO-d6, 75 MHz) d (ppm)
28.0 (2C), 31.0 (2C), 45.7, 98.7 (2C), 104.3 (2C), 126.5 (2C), 129.5,
130.8 (2C), 134.6, 138.8 (2C), 139.8 (2C), 151.1 (2C), 158.6 (2C),
194.0; IR (KBr) nmax 3378.9, 3275.2, 1687.2, 1558.2 cmꢂ1; MS
(ESI) 509.1 ([M + H]+); anal. cald for C24H21ClN6O5 C, 56.64; H,
4.16; N, 16.51% found: C, 56.70; H, 4.19; N, 16.55%.
1
8400. H NMR and 13C NMR Spectra were recorded on Bruker
Avance-DPX 300 MHz and 75 MHz FT NMR in DMSO-d6 using
TMS as an internal standard. Chemical shis (d units) are given
from TMS (0 ppm) and coupling constants are expressed in
Hertz (Hz). Chemical shis for DMSO-d6 were reported at
around 3.36 and 2.50 ppm respectively (d units). Mass spectra
were recorded on ESQUIRE 3000 Mass spectrometer. All exper-
iments were monitored by Thin Layer Chromatography (TLC).
TLC was performed on pre-coated silica gel plates (Merck).
3e. Pink solid. Yield: 447 mg (81%); mp. 275–279 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d (ppm) 3.18 (s, 6H), 3.43 (s, 6H), 6.02 (s,
2H), 6.22 (s, 1H), 7.73 (d, J ¼ 8.49 Hz, 2H), 7.96 (d, J ¼ 8.43 Hz,
2H), 11.97 (s, 2H); 13C NMR (DMSO-d6, 75 MHz) d (ppm) 28.0
General procedure for the synthesis of bis(pyrrolo[2,3-d]
pyrimidinyl)methanes 3
In a typical experimental procedure, acetophenone 2a (0.120 g, (2C), 31.1 (2C), 46.7, 98.7 (2C), 104.3 (2C), 126.5 (2C), 129.5,
1 mmol), I2 (0.3795 g, 1.5 mmol) and DMSO (5 mL) were rst 130.8 (2C), 134.6, 138.8 (2C), 139.8 (2C), 151.1 (2C), 158.6 (2C),
treated at 90 ꢀC for 2 h. The resulting mixture was then cooled to 194.0; IR (KBr) nmax 3388.7, 3279.2, 1689.1, 1555.4 cmꢂ1; MS
room temperature and reacted with 1,3-dimethylpyrrolo[2,3-d] (ESI) 554.3 ([M + H]+); anal. cald for C24H21BrN6O5 C, 52.09; H,
pyrimidine-2,4-dione 1a (0.362 g, 2 mmol) at room tempera- 3.83; N, 15.19% found: C, 52.16; H, 3.89; N, 15.25%.
ture for 1 h. Aer completion (monitored by TLC) of the reac-
3f. Pinkish orange solid. Yield: 420 mg (81%); mp. 273–277
1
tion, 5% aqueous sodium thiosulphate solution (5 mL) was ꢀC; H NMR (DMSO-d6, 300 MHz) d (ppm) 3.18 (s, 6H), 3.43 (s,
added to the reaction mixture and extracted with ethyl acetate 6H), 6.07 (s, 2H), 6.22 (s, 1H), 8.09–8.37 (m, 4H), 11.77 (s, 2H);
(5 mL ꢁ 3 mL). The combined solvent was evaporated under 13C NMR (DMSO-d6, 75 MHz) d (ppm) 28.0 (2C), 31.0 (2C), 46.5,
reduced pressure and the product was puried by column 98.8 (2C), 104.5 (2C), 124.5 (2C), 126.0 (2C), 129.0 (2C), 130.3,
chromatography on silica gel using 2 : 8 ratio of hex- 133.3, 139.9 (2C), 151.1 (2C), 158.6 (2C), 194.1; IR (KBr) nmax
ane : ethylacetate as eluent. The structure of the compound was 3387.2, 3281.2, 1679.1, 1565.4 cmꢂ1; MS (ESI) 520.2 ([M + H]+);
ascertained as bis(pyrrolo[2,3-d]pyrimidinyl)methane derivative anal. cald for C24H21N7O7 C, 55.49; H, 4.07; N, 18.87% found: C,
3a from the spectroscopic data and elemental analysis. Simi- 55.56; H, 4.19; N, 18.95%.
larly compounds 3b–p were synthesized and characterized.
3g. Pink solid. Yield: 379 mg (79%); mp. 275–279 ꢀC; 1H NMR
1
ꢀ
3a. Purple solid. Yield: 388 mg (82%); mp. 279–280 C; H (DMSO-d6, 300 MHz) d (ppm) 3.19 (s, 6H), 3.41 (s, 6H), 6.08 (s,
NMR (DMSO-d6, 300 MHz) d (ppm) 3.18 (s, 6H), 3.42 (s, 6H), 6.03 2H), 6.20 (s, 1H), 6.90–7.48 (m, 3H), 11.80 (s, 2H, NH); 13C NMR
(s, 2H), 6.14 (s, 1H), 7.26–8.04 (m, 5H), 11.77 (s, 2H, NH); 13C (DMSO-d6, 75 MHz) d (ppm) 28.0 (2C), 31.0 (2C), 38.3, 98.3 (2C),
NMR (DMSO-d6, 75 MHz) d (ppm) 28.0 (2C), 31.0 (2C), 45.8, 98.7 102.6 (2C), 125.6, 126.2, 127.2, 131.7 (2C), 139.4 (2C), 144.7,
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3n. Brown solid. Yield: 382 mg (78%); mp. > 300 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d (ppm) 3.32 (s, 6H), 6.08 (s, 2H), 6.22
(s, 1H), 7.18–7.35 (m, 4H), 10.75 (s, 2H, NH), 11.59 (s, 2H, NH);
13C NMR (DMSO-d6, 75 MHz) d (ppm) 28.0 (2C), 46.5, 98.8 (2C),
104.5 (2C), 124.5 (2C), 126.0 (2C), 129.0 (2C), 130.3, 133.3, 139.9
(2C), 151.1 (2C), 158.6 (2C), 194.1; IR (KBr) nmax 3387.5, 3272.6,
1657.8, 1610.5 cmꢂ1; MS (ESI) 492.5 ([M + H]+); anal. cald for
151.0 (2C), 158.6 (2C), 194.0; IR (KBr) nmax 3378.9, 3277.1,
1677.5, 1556.2 cmꢂ1; MS (ESI) 481.6 ([M + H]+); anal. cald for
C
22H20N6O5S C, 54.99; H, 4.20; N, 17.49% found: C, 55.06; H,
4.25; N, 17.58%.
3h. Pink solid. Yield: 430 mg (82%); mp. 277–280 ꢀC; 1H
NMR (DMSO-d6, 300 MHz) d (ppm) 3.18 (s, 6H), 3.44 (s, 6H), 6.10
(s, 2H), 6.35 (s, 1H), 7.61–8.74 (m, 7H), 11.80 (s, 2H); 13C NMR
(DMSO-d6, 75 MHz) d (ppm) 28.0 (2C), 31.0 (2C), 45.9, 98.8 (2C),
104.2 (2C), 124.6, 126.9 (2C), 127.6, 128.1, 128.9, 129.3, 130.0,
130.6, 132.5, 133.2, 135.4, 139.8 (2C), 151.1 (2C), 158.6 (2C),
194.5; IR (KBr) nmax 3386.4, 3284.9, 1669.5, 1562.1 cmꢂ1; MS
(ESI) 525.3 ([M + H]+); anal. cald for C28H24N6O5 C, 64.11; H,
4.61; N, 16.02% found: C, 64.21; H, 4.69; N, 16.15%.
C
22H17N7O7 C, 53.77; H, 3.49; N, 19.95% found: C, 53.82; H,
3.57; N, 20.06%.
3o. Brown solid. Yield: 339 mg (75%); mp. > 300 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d (ppm) 3.19 (s, 6H), 6.07 (s, 2H), 6.15
(s, 1H), 6.92–7.47 (m, 3H), 10.42 (s, 2H, NH), 11.80 (s, 2H, NH);
13C NMR (DMSO-d6, 75 MHz) d (ppm) 28.1 (2C), 38.3, 98.3 (2C),
102.6 (2C), 125.6, 126.2, 127.2, 131.7 (2C), 139.4 (2C), 144.7,
151.0 (2C), 158.6 (2C), 194.0; IR (KBr) nmax 3369.5, 3270.2,
1688.5, 1553.2 cmꢂ1; MS (ESI) 453.5 ([M + H]+); anal. cald for
3i. Brown solid. Yield: 348 mg (78%); mp. > 300 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d (ppm) 3.18 (s, 6H), 6.03 (s, 2H), 6.17
(s, 1H), 7.40–7.68 (m, 5H), 10.73 (s, 2H, NH), 11.58 (s, 2H, NH);
13C NMR (DMSO-d6, 75 MHz) d (ppm) 28.0 (2C), 45.8, 98.7 (2C),
104.1 (2C), 126.9 (2C), 129.0 (2C), 129.3 (2C), 133.9, 135.93,
139.7 (2C), 151.1 (2C), 158.6 (2C), 194.4; IR (KBr) nmax; 3370.1,
3278.5, 1656.3, 1617.1 cmꢂ1; MS (ESI) 447.4 ([M + H]+); anal.
cald for C22H18N6O5 C, 59.19; H, 4.06; N, 18.83% found: C,
59.26; H, 4.14; N, 18.89%.
C
20H16N6O5S C, 53.09; H, 3.56; N, 18.57% found: C, 53.15; H,
3.61; N, 18.64%.
3p. Brown solid. Yield: 386 mg (78%); mp. > 300 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d (ppm) 3.18 (s, 6H), 6.11 (s, 2H), 6.37
(s, 1H), 7.60–8.75 (m, 7H), 10.76 (s, 2H), 11.58 (s, 2H); 13C NMR
(DMSO-d6, 75 MHz) d (ppm) 28.0 (2C), 45.9, 98.8 (2C), 104.2 (2C),
124.6, 126.9 (2C), 127.6, 128.1, 128.9, 129.3, 130.0, 130.6, 132.5,
133.2, 135.4, 139.8 (2C), 151.1 (2C), 158.6 (2C), 194.5; IR (KBr)
nmax 3387.2, 3274.8, 1679.2, 1560.1 cmꢂ1; MS (ESI) 497.5 ([M +
H]+); anal. cald for C26H20N6O5 C, 62.90; H, 4.06; N, 16.93%
found: C, 63.11; H, 4.09; N, 17.15%.
3j. Brown solid. Yield: 354 mg (77%); mp. > 300 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d (ppm) 2.31 (s, 3H), 3.19 (s, 6H), 6.04
(s, 2H), 6.22 (s, 1H), 7.10–7.21 (m, 4H), 10.75 (s, 2H, NH), 11.71
(s, 2H, NH); 13C NMR (DMSO-d6, 75 MHz) d (ppm) 21.5, 28.0
(2C), 45.7, 98.7 (2C), 104.1 (2C), 127.0 (2C), 129.1 (2C), 129.8
(2C), 133.4, 139.7 (2C), 144.4, 151.1 (2C), 158.6 (2C), 194.0 IR
(KBr) nmax 3372.1, 3267.9, 1680.2, 1557.6 cmꢂ1; MS (ESI) 461.4
([M + H]+); anal. cald for C23H20N6O5 C, 60.02; H, 4.38; N,
18.25% found: C, 60.09; H, 4.47; N, 18.34%.
General procedure for the synthesis of compound 7
In a typical experimental procedure, 1,3-dimethylpyrrolo[2,3-d]
3k. Brown solid. Yield: 366 (77%); mp. > 300 ꢀC; 1H NMR pyrimidine-2,4-dione 1a (0.181 g, 1 mmol), 5-benzylidene-1,3-
(DMSO-d6, 300 MHz) d (ppm) 3.17 (s, 6H), 3.67 (s, 3H), 6.01 dimethylpyrimidine-2,4,6(1H,3H,5H)-trione 6 (0.244 g, 1 mmol),
(s, 2H), 6.12 (s, 1H), 6.71–7.26 (m, 4H), 10.71 (s, 2H, NH), 11.55 I2 (0.006 g, 5 mol%) and acetonitrile (5 mL) were stirred at room
(s, 2H, NH); 13C NMR (DMSO-d6, 75 MHz) d (ppm) 28.0 (2C), temperature for 2 h. Aer completion (monitored by TLC) of the
42.4, 55.5, 98.4 (2C), 102.9 (2C), 114.2 (2C), 128.5, 129.7 (2C), reaction, the solid product obtained was ltered and recrystal-
132.5 (2C), 132.9, 139.6 (2C), 151.1 (2C), 158.7 (2C), 194.0; IR lized from ethanol. The structure of the compound was ascer-
(KBr) nmax 3386.2, 3275.4, 1665.5, 1626.6 cmꢂ1; MS (ESI) 477.5 tained as 7a from the spectroscopic data and elemental
([M + H]+); anal. cald for C23H20N6O6 C, 57.98; H, 4.23; N, analysis. Similarly compounds 7b–e were synthesized and
17.64% found: C, 58.02; H, 4.31; N, 17.70%.
characterized.
3l. Brown solid. Yield: 374 mg (78%); mp. > 300 ꢀC; 1H NMR
7a. White solid. Yield: 372 mg (88%); mp. 186.5–187.1 ꢀC; 1H
(DMSO-d6, 300 MHz) d (ppm) 3.25 (s, 6H), 6.06 (s, 2H), 6.19 (s, NMR (DMSO-d6, 300 MHz) d (ppm) 2.90 (s, 3H), 3.07 (s, 3H), 3.20
1H), 7.10–7.70 (m, 4H), 10.77 (s, 2H, NH), 11.58 (s, 2H, NH); 13
C
(s, 3H), 3.37 (s, 3H), 4.37 (d, J ¼ 4.17 Hz, 1H), 5.20 (d, J ¼ 3.9 Hz,
NMR (DMSO-d6, 75 MHz) d (ppm) 28.0 (2C), 45.7, 98.7 (2C), 1H), 6.26 (s, 1H), 6.73–7.05 (m, 5H), 11.65 (s, 1H); 13C NMR
104.3 (2C), 126.5 (2C), 129.5, 130.8 (2C), 134.6, 138.8 (2C), 139.8 (DMSO-d6, 75 MHz) d (ppm) 28.0, 28.2, 28.5, 31.0, 40.9, 52.7,
(2C), 151.1 (2C), 158.6 (2C), 194.0; IR (KBr) nmax 3383.5, 3275.4, 98.6, 103.4, 115.0, 119.0, 124.9, 128.6, 130.0, 130.4, 139.2, 151.1,
1658.1, 1615.5 cmꢂ1; MS (ESI) 481.3 ([M + H]+); anal. cald for 151.8, 154.8, 158.6, 167.8, 168.4; IR (KBr) nmax 3555.7, 3471.2,
C
22H17ClN6O5 C, 54.95; H, 3.56; N, 17.48% found: C, 55.15; H, 1741.2, 1665.1 cmꢂ1; MS (ESI) 424.5 ([M + H]+); anal. cald for
3.61; N, 17.51%. 21H21N5O5 C, 59.57; H, 5.00; N, 16.54% found: C, 59.71; H,
3m. Brown solid. Yield: 408 (78%); mp. > 300 ꢀC; H NMR 5.19; N, 16.65%.
C
1
(DMSO-d6, 300 MHz) d (ppm) 3.32 (s, 6H), 6.07 (s, 2H), 6.25 (s, 1H),
7b. White solid. Yield: 398 mg (88%); mp. 185.4–186.5 ꢀC; 1H
7.21–7.43 (m, 4H), 10.75 (s, 2H, NH), 11.58 (s, 2H, NH); 13C NMR NMR (DMSO-d6, 300 MHz) d (ppm) 2.90 (s, 3H), 3.07 (s, 3H), 3.20
(DMSO-d6, 75 MHz) d (ppm) 28.0 (2C), 46.7, 98.7 (2C), 104.3 (2C), (s, 3H), 3.37 (s, 3H), 3.68 (s, 3H), 4.38 (d, J ¼ 3.18 Hz, 1H), 5.21
126.5 (2C), 129.5, 130.8 (2C), 134.6, 138.8 (2C), 139.8 (2C), 151.1 (d, J ¼ 0.60 Hz, 1H), 6.26 (s, 1H), 6.64–6.82 (m, 5H), 11.66 (s, 1H);
(2C), 158.6 (2C), 194.0; IR (KBr) nmax 3398.2, 3271.2, 1657.2, 1613.5 13C NMR (DMSO-d6, 75 MHz) d (ppm) 28.1, 28.2, 28.5, 31.0, 50.7,
cmꢂ1; MS (ESI) 525.4 ([M + H]+); anal. cald for C22H17BrN6O5 C, 58.8, 98.6, 103.4, 115.1, 119.0, 124.9, 128.6, 130.0, 130.3, 139.3,
50.30; H, 3.26; N, 15.21% found: C, 50.42; H, 3.32; N, 15.29%.
151.1, 151.8, 154.8, 158.6, 167.8, 168.4; IR (KBr) nmax 3547.3,
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3470.9, 1745.3, 1662 cmꢂ1; MS (ESI) 454.6 ([M + H]+); anal. cald NH), 11.68 (s, 2H, NH); 13C NMR (DMSO-d6, 75 MHz) d 28.6 (2C),
for C22H23N5O6 C, 58.27; H, 5.11; N, 15.44% found: C, 58.39; H, 42.2, 99.1 (2C), 103.0 (2C), 125.2, 127.0 (2C), 128.8 (2C), 132.1
5.29; N, 15.55%.
(2C), 140.1, 141.1 (2C), 151.0 (2C), 159.2 (2C); IR (KBr) nmax
7c. White solid. Yield: 406 mg (87%); mp. 187.3–188.2 ꢀC; 1H 3372.5, 3279.4, 1658.7, 1615.7 cmꢂ1; MS (ESI) 419.4 ([M + H]+);
NMR (DMSO-d6, 300 MHz) d (ppm) 2.90 (s, 3H), 3.07 (s, 3H), 3.20 anal. cald for C21H18N6O4 C, 60.27; H, 4.30; N, 20.08% found: C,
(s, 3H), 3.37 (s, 3H), 4.38 (d, J ¼ 3.24 Hz, 1H), 5.20 (d, J ¼ 3.00 Hz, 60.28; H, 4.34; N, 20.09%.
1H), 6.27 (s, 1H), 6.64–7.06 (m, 4H), 11.65 (s, 1H); 13C NMR
9c. Brown solid; yield: 360 mg (84%); mp. > 300 ꢀC; 1H NMR
(DMSO-d6, 75 MHz) d (ppm) 28.0, 28.2, 28.5, 31.0, 40.9, 52.7, (DMSO-d6, 300 MHz) d 3.32 (s, 6H), 3.40 (s, 3H), 5.59 (s, 1H), 5.63
98.6, 103.4, 115.0, 119.0, 124.9, 128.6, 130.0, 130.4, 139.2, 151.1, (s, 1H), 5.67 (s, 1H), 6.74–7.14 (m, 5H), 10.71 (br, 1H, NH), 11.68
151.8, 154.8, 158.6, 167.8, 168.3; IR (KBr) nmax 3545.3, 3470.1, (br, 2H, NH); 13C NMR (DMSO-d6, 75 MHz) d 28.0, 28.6, 29.8,
1740.1, 1669.4 cmꢂ1; MS (ESI) 469.1 ([M + H]+); anal. cald for 36.3, 98.3, 99.0, 102.9, 104.2, 117.2, 119.3, 127.3, 128.8, 132.3,
C
21H20N6O7 C, 53.85; H, 4.30; N, 17.94% found: C, 53.99; H, 139.5, 140.8, 140.9, 151.0, 151.2, 154.9, 158.6, 159.2, 159.5; IR
4.49; N, 18.15%.
(KBr) nmax 3375.4, 3278.2, 1657.3, 1613.2 cmꢂ1; MS (ESI) 433.4
7d. White solid. Yield: 377 mg (88%); mp. 185.4–187.3 ꢀC; 1H ([M + H]+); anal. cald for C22H20N6O4 C, 61.10; H, 4.66; N,
NMR (DMSO-d6, 300 MHz) d (ppm) 2.90 (s, 3H), 3.06 (s, 3H), 3.20 19.43% found: C, 61.22; H, 4.67; N, 19.56%.
(s, 3H), 3.37 (s, 3H), 4.37 (d, J ¼ 4.14 Hz, 1H), 5.21 (d, J ¼ 2.94 Hz,
9d. Brown solid; yield: 377 mg (82%); mp. > 300 ꢀC; 1H NMR
1H), 6.25 (s, 1H), 6.62–7.03 (m, 3H), 11.64 (s, 1H); 13C NMR (DMSO-d6, 300 MHz) d 3.32 (s, 6H), 3.40 (s, 3H), 3.70 (s, 3H), 5.59
(DMSO-d6, 75 MHz) d (ppm) 28.0, 28.1, 28.5, 31.0, 40.8, 52.5, (s, 1H), 5.63 (s, 1H), 5.67 (s, 1H), 6.74–6.88 (m, 4H), 10.70 (br,
98.5, 103.6, 125.1, 126.2, 127.2, 130.4, 140.1, 145.3, 151.7, 154.5, 1H, NH), 11.69 (br, 2H, NH); 13C NMR (DMSO-d6, 75 MHz) d
158.3, 167.7, 168.2; IR (KBr) nmax 3543.2, 3475.4, 1745.2, 1665.3 28.0, 28.6, 29.8, 36.4, 58.5, 98.3, 99.0, 102.9, 104.2, 117.2, 119.3,
cmꢂ1; MS (ESI) 430.5 ([M + H]+); anal. cald for C19H19N5O5S C, 127.3, 128.8, 132.3, 139.5, 140.8, 140.97, 151.0, 151.2, 154.9,
53.14; H, 4.46; N, 16.31% found: C, 53.17; H, 4.49; N, 16.35%.
158.6, 159.2, 159.5; IR (KBr) nmax 3369.4, 3272.5, 1656.7, 1619.2
7e. White solid. Yield: 338 mg (87%); mp. 183.2–185.1 ꢀC; 1H cmꢂ1; MS (ESI) 463.2 ([M + H]+); anal. cald for C23H22N6O5 C,
NMR (DMSO-d6, 300 MHz) d (ppm) 0.87 (m, 6H), 2.33 (m, 1H), 59.73; H, 4.79; N, 18.17% found: C, 59.82; H, 4.87; N, 18.26%.
2.90 (s, 3H), 3.05 (s, 3H), 3.20 (s, 3H), 3.37 (s, 3H), 4.37 (d, J ¼
9e. Brown solid; yield: 380 mg (80%); mp. > 300 ꢀC; 1H NMR
3.51 Hz, 1H), 5.20 (d, J ¼ 2.94 Hz, 1H), 6.23 (s, 1H), 11.66 (s, 1H); (DMSO-d6, 300 MHz) d 3.32 (s, 6H), 3.38 (s, 3H), 5.52 (s, 1H), 5.61
13C NMR (DMSO-d6, 75 MHz) d (ppm) 21.4 (2C), 28.0, 28.2, 28.5 (s, 1H), 5.69 (s, 1H), 6.31–7.14 (m, 4H), 10.71 (br, 1H, NH), 11.68
(2C), 31.2, 33.0, 40.7, 98.5, 103.5, 135.2, 139.3, 151.7, 154.5, (br, 2H, NH); 13C NMR (DMSO-d6, 75 MHz) d 28.0, 28.6, 29.8,
158.8, 166.2, 168.7; IR (KBr) nmax 3532.1, 3473.6, 1730.5, 1665.2 36.4, 98.3, 99.0, 102.9, 104.2, 117.2, 119.3, 127.3, 128.8, 132.3,
cmꢂ1; MS (ESI) 390.3 ([M + H]+); anal. cald for C18H23N5O5 C, 139.5, 140.8, 140.9, 151.0, 151.2, 154.9, 158.6, 159.2, 159.5; IR
55.52; H, 5.95; N, 17.98% found: C, 55.53; H, 5.96; N, 17.99%.
(KBr) nmax 3360.5, 3273.2, 1659.1, 1629.3 cmꢂ1; MS (ESI) 478.5
([M + H]+); anal. cald for C22H19N7O6 C, 55.35; H, 4.01; N,
20.54% found: C, 55.42; H, 4.17; N, 20.62%.
9f. Brown solid; yield: 414 mg (90%); mp. > 300 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d 3.32 (s, 6H), 3.38 (s, 6H), 3.60 (s, 3H), 5.53
General procedure for the synthesis of bis(pyrrolo[2,3-d]
pyrimidinyl)methanes 9
In a typical experimental procedure, 5-((1,3-dimethyl-2,4-dioxo- (s, 1H), 5.64 (s, 1H), 5.71 (s, 1H), 6.69–7.19 (m, 5H), 11.68 (s, 1H,
2,3,4,7-tetrahydro-1H-pyrrolo[2,3-d]pyrimidin-6-yl)(phenyl)- NH); 13C NMR (DMSO-d6, 75 MHz) d 28.0, 28.6, 29.8, 30.0, 31.0,
methyl)-1,3-dimethylpyrimidine-2,4,6-(1H,3H,5H)-trione 7a (0.423 36.4, 98.3, 99.0, 102.9, 104.2, 117.2, 119.3, 127.3, 128.8, 132.3,
g, 1 mmol), 1,3-dimethylpyrrolo[2,3-d]pyrimidine-2,4-dione 1a 139.5, 140.8, 140.9, 151.0, 151.2, 154.9, 158.6, 159.2, 159.5; IR
(0.181 g, 1 mmol), I2 (0.006 g, 5 mol%) and acetonitrile (5 mL) (KBr) nmax 3362.4, 3276.4, 1657.5, 1622.4 cmꢂ1; MS (ESI) 461.6
were mixed and allowed to run under reux condition for 3 h. ([M + H]+); anal. cald for C24H24N6O4 C, 62.60; H, 5.25; N,
Aer completion (monitored by TLC) of the reaction, the solid 18.25% found: C, 62.72; H, 5.27; N, 18.32%.
product obtained was ltered and recrystallized from ethanol.
9g. Brown solid; yield: 436 mg (89%); mp. > 300 ꢀC; 1H NMR
The structure of the compound was ascertained as bis(pyrrolo (DMSO-d6, 300 MHz) d 3.32 (s, 6H), 3.38 (s, 6H), 3.60 (s, 3H), 3.70
[2,3-d]pyrimidinyl)methane derivative 9a from the spectro- (s, 3H), 5.50 (s, 1H), 5.61 (s, 1H), 5.72 (s, 1H), 6.49–7.09 (m, 4H),
scopic data and elemental analysis.
11.68 (s, 1H, NH); 13C NMR (DMSO-d6, 75 MHz) d 28.0, 28.6,
9a. Pink solid; yield: 423 mg (95%); mp. 288–290 ꢀC; 1H NMR 29.8, 30.0, 31.0, 36.4, 58.5, 98.3, 99.1, 102.8, 104.2, 117.2, 119.3,
(DMSO-d6, 300 MHz) d 3.19 (s, 6H), 3.39 (s, 6H), 5.40 (s, 1H), 5.76 127.3, 128.8, 132.4, 139.5, 140.8, 140.9, 151.0, 151.2, 154.9,
(s, 2H), 7.22–7.39 (m, 5H), 11.74 (s, 2H, NH); 13C NMR (DMSO- 158.6, 159.2, 159.5; IR (KBr) nmax 3361.5, 3174.4, 1667.5, 1620.4
d6, 75 MHz) d 28.0 (2C), 31.1 (2C), 43.2, 98.4 (2C), 103.1 (2C), cmꢂ1; MS (ESI) 491.4 ([M + H]+); anal. cald for C25H26N6O5 C,
127.5, 128.7 (2C), 128.8 (2C), 132.1 (2C), 139.6 (2C), 141.0, 151.1 61.22; H, 5.34; N, 17.13% found: C, 61.32; H, 5.37; N, 17.22%.
(2C), 158.7 (2C); IR (KBr) nmax 3373.5, 3278.5, 1687.2, 1557.6
cmꢂ1; MS (ESI) 447.5 ([M + H]+); anal. cald for C23H22N6O4 C, (DMSO-d6, 300 MHz) d 3.32 (s, 6H), 3.39 (s, 6H), 3.59 (s, 3H), 5.54
9h. Brown solid; yield: 439 mg (87%); mp. > 300 ꢀC; 1H NMR
61.87; H, 4.92; N, 18.82% found: C, 61.88; H, 4.93; N, 18.83%.
(s, 1H), 5.63 (s, 1H), 5.75 (s, 1H), 6.35–7.14 (m, 4H), 11.65 (s, 1H,
9b. Pinkish violet solid; Yield: 384 mg (92%); mp. > 300 C; NH); 13C NMR (DMSO-d6, 75 MHz) d 28.0, 28.6, 29.8, 30.0, 31.0,
1H NMR (DMSO-d6, 300 MHz) d 3.17 (s, 3H), 3.26 (s, 3H), 5.38 (s, 36.4, 98.3, 99.1, 102.8, 104.2, 117.2, 119.3, 127.3, 128.8, 132.4,
1H), 5.45 (s, 1H), 5.72 (s, 1H), 7.09–7.59 (m, 5H), 10.32 (s, 2H, 139.5, 140.8, 140.9, 151.0, 151.2, 154.9, 158.6, 159.2, 159.5; IR
ꢀ
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(KBr) nmax 3365.6, 3170.5, 1669.4, 1625.3 cmꢂ1; MS (ESI): 506.5
([M + H]+); anal. cald for C24H23N7O6 C, 57.04; H, 4.59; N,
19.40% found: C, 57.12; H, 4.67; N, 19.50%.
9o. Brown solid; yield: 357 mg (84%); mp. > 300 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d 0.88 (m, 6H), 2.35 (m, 1H), 3.19 (s, 6H),
3.40 (s, 6H), 3.53 (s, 3H), 3.61 (d, 1H), 6.26 (s, 2H), 11.67 (s, 1H,
NH); 13C NMR (DMSO-d6, 75 MHz) d 21.4 (2C), 28.2 (2C), 30.3
(3C), 31.5, 45.2, 98.5 (2C), 101.7 (2C), 134.0 (2C), 140.2 (2C),
153.1 (2C), 157.2 (2C); IR (KBr) nmax: 3381.4, 3262.7, 1651.8,
1619.2 cmꢂ1; MS (ESI): 427.8 ([M + H]+). Anal. cald for
9i. Brown solid; yield: 310 mg (70%); mp. > 300 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d 3.32 (s, 6H), 3.39 (s, 3H), 3.59 (s, 3H), 5.53
(s, 1H), 5.65 (s, 1H), 5.77 (s, 1H), 6.73–7.14 (m, 5H), 10.70 (s, 1H,
NH), 11.70 (s, 1H, NH); 13C NMR (DMSO-d6, 75 MHz) d 28.0,
28.5, 29.7, 31.0, 36.4, 98.3, 99.2, 102.8, 104.2, 117.2, 119.3, 127.3,
128.8, 132.4, 139.5, 140.8, 140.9, 151.1, 151.2, 154.9, 158.6,
C
21H26N6O4: C, 59.14; H, 6.14; N, 19.71%; found: C, 59.16; H,
6.15; N, 19.72%.
159.3, 159.5; IR (KBr) nmax: 3362.4, 3179.3, 1675.4, 1631.4 cmꢂ1
;
9p. Brown solid; yield: 316 mg (70%); mp. > 300 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d 3.19 (s, 6H), 3.35 (s, 3H), 3.45 (s, 3H), 5.62
(s, 1H), 5.95 (s, 2H), 6.89–7.48 (m, 3H), 10.59 (s, 1H, NH), 11.68
(s, 1H, NH); 13C NMR (DMSO-d6, 75 MHz) d 26.8 (2C), 29.0, 30.2,
39.1, 98.2 (2C), 102.5 (2C), 125.5, 126.3, 127.2, 132.8 (2C), 140.3
(2C), 145.5, 151.1 (2C), 158.3 (2C); IR (KBr) nmax: 3371.5, 3269.2,
1650.4, 1619.3 cmꢂ1; MS (ESI): 453.2 ([M + H]+). Anal. cald for
MS (ESI): 447.8 ([M + H]+). Anal. Cald for C23H22N6O4: C, 61.87;
H, 4.97; N, 18.82%; found: C, 61.92; H, 5.07; N, 18.94%.
9j. Brown solid; yield: 327 mg (69%); mp. > 300 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d 3.32 (s, 6H), 3.39 (s, 3H), 3.58 (s, 3H), 3.70
(s, 3H), 5.50 (s, 1H), 5.63 (s, 1H), 5.74 (s, 1H), 6.71–7.12 (m, 4H),
10.71 (s, 1H, NH), 11.64 (s, 1H, NH); 13C NMR (DMSO-d6, 75
MHz) d 28.0, 28.5, 29.7, 31.0, 36.4, 58.6, 98.3, 99.2, 102.8, 104.2,
117.2, 119.3, 127.3, 128.8, 132.4, 139.5, 140.8, 140.9, 151.1,
151.2, 154.9, 158.6, 159.3, 159.5; IR (KBr) nmax 3362.4, 3179.3,
1675.4, 1631.4 cmꢂ1; MS (ESI) 477.1 ([M + H]+); anal. cald for
C
21H20N6O4S: C, 55.74; H, 4.46; N, 18.57%; found: C, 56.76; H,
4.47; N, 18.58%.
9q. Brown solid; yield: 280 mg (68%); mp. > 300 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d 0.87 (m, 6H), 2.36 (m, 1H), 3.19 (s, 6H),
3.41 (s, 3H), 3.54 (s, 3H), 3.61 (d, 1H), 6.25 (s, 2H), 10.70 (s, 1H,
NH), 11.67 (s, 1H, NH); 13C NMR (DMSO-d6, 75 MHz) d 21.4 (2C),
29.1 (2C), 30.3 (2C), 31.5, 45.2, 98.5 (2C), 101.7 (2C), 134.1 (2C),
140.2 (2C), 153.1 (2C), 157.2 (2C); IR (KBr) nmax: 3383.7, 3252.3,
1655.6, 1615.7 cmꢂ1; MS (ESI): 413.4 ([M + H]+). Anal. cald for
C
24H24N6O5 C, 60.50; H, 5.08; N, 17.64% found: C, 60.62; H,
5.17; N, 17.74%.
9k. Brown solid; yield: 333 mg (68%); mp. > 300 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d 3.33 (s, 6H), 3.38 (s, 3H), 3.56 (s, 3H), 5.54
(s, 1H), 5.67 (s, 1H), 5.76 (s, 1H), 6.72–7.15 (m, 4H), 10.73 (s, 1H,
NH), 11.67 (s, 1H, NH); 13C NMR (DMSO-d6, 75 MHz) d 28.0,
28.5, 29.7, 31.0, 36.4, 98.3, 99.2, 102.8, 104.2, 117.2, 119.3, 127.3,
128.8, 132.4, 139.5, 140.8, 140.9, 151.1, 151.2, 154.9, 158.6,
C
20H24N6O4: C, 58.24; H, 5.87; N, 20.38%; found: C, 58.27; H,
5.88; N, 20.39%.
159.3, 159.5; IR (KBr) nmax 3364.7, 3175.2, 1676.3, 1635.6 cmꢂ1
;
Acknowledgements
MS (ESI) 492.4 ([M + H]+); anal. cald for C23H21N7O6 C, 56.21; H,
4.31; N, 19.95% found: C, 56.32; H, 4.37; N, 20.08%.
We thank the CSIR, New Delhi for nancial assistance (CAAF-
NE project). MS thanks the DST, New Delhi for the INSPIRE
Fellowship.
9l. Brown solid; yield: 363 mg (83%); mp. > 300 ꢀC; 1H NMR
(DMSO-d6, 300 MHz) d 3.19 (s, 6H), 3.40 (s, 3H), 5.66 (s, 1H), 5.93
(s, 2H), 6.91–7.46 (m, 3H), 10.30 (s, 1H, NH), 11.67 (s, 2H, NH);
13C NMR (DMSO-d6, 75 MHz) d 27.9, 31.0 (2C), 38.3, 98.3 (2C),
102.6 (2C), 125.6, 126.2, 127.2, 131.7 (2C), 140.0 (2C), 145.7,
150.9 (2C), 157.6 (2C); IR (KBr) nmax: 3376.3, 3275.3, 1659.2,
1610.2 cmꢂ1; MS (ESI): 439.2 ([M + H]+). Anal. cald for
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9m. Brown solid; yield: 326 mg (82%); mp. > 300 ꢀC; 1H NMR
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60646 | RSC Adv., 2014, 4, 60640–60647
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RSC Adv., 2014, 4, 60640–60647 | 60647