Synthesis and inhibitory activity evaluation of 2,6-disubstituted purine derivatives

Article abstract of DOI:10.1002/jhet.1959

A series of novel 2,6-disubstituted purine derivatives were designed and synthesized from 2,6-dichloropurine. The structures of target compounds were determined by ¹H-NMR, ¹³C-NMR, and HRMS. The synthesized compounds were evaluated for their inhibitory activities against lung cancer cell lines of A549 and liver cancer cell lines of Bel-7402. 2-(4-Benzyloxy-phenylamino)-6-(cyclohexylamino)purine(3), 2-(4-chloro-phenylamino)-6-(n-butylamino)purine (5), 2-(4-morpholinoamino)-6-(4-hydroxy-phenylamino)purine (9), and 2-(4-O-galactosyl-phenylamino)-6-(cyclohexylamino)purine (12) exhibited moderate inhibitory activity.

Full text of DOI:10.1002/jhet.1959

March 2015
Synthesis and Inhibitory Activity Evaluation of 2,6-Disubstituted Purine
Derivatives
473
c
a
a
Hongxia Liu,a,b Libo Li, Shaikh Qurat-ul-ain, and Tao Jiang
*
aKey Laboratory of Marine Drugs, Chinese Ministry of Education, Shandong Provincial, School of Medicine and
Pharmacy, Ocean University of China, Qingdao, Shandong 266003, People’s Republic of China
bCollege of Chemistry and Chemical Engineering, Qiqihar University, Qiqihar, Heilongjiang 161006, China
cDepartment of Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, People’s Republic of China
*
E-mail: jiangtao@ouc.edu.cn
Received November 7, 2012
DOI 10.1002/jhet.1959
Published online 23 May 2014 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel 2,6-disubstituted purine derivatives were designed and synthesized from 2,6-dichloro-
purine. The structures of target compounds were determined by 1H-NMR, 13C-NMR, and HRMS. The
synthesized compounds were evaluated for their inhibitory activities against lung cancer cell lines of
A549 and liver cancer cell lines of Bel-7402. 2-(4-Benzyloxy-phenylamino)-6-(cyclohexylamino)purine
(3), 2-(4-chloro-phenylamino)-6-(n-butylamino)purine (5), 2-(4-morpholinoamino)-6-(4-hydroxy-phenyla-
mino)purine (9), and 2-(4-O-galactosyl-phenylamino)-6-(cyclohexylamino)purine (12) exhibited moderate
inhibitory activity.
J. Heterocyclic Chem, 52, 473 (2015).
INTRODUCTION
The aim of our works is to study the effect of different
2-position substituent on the purine scaffold on their
anticancer activities. Various 2,6-disubstituted purine
analogs including 2-(4-O-galactosides-phenylamino)-
6-(cyclohexylamino)purine (11–14) have been synthe-
sized from 2,6-dichloropurine herein. On the basis of our
preliminary results, 2,6-disubstituted purine derivatives have
been chosen as our target compound, and the solubility of
these compounds can be improved also.
Purines and aminopurines are classes of important
pharmaceutical compounds with significant physiological
and pharmacological properties [1,2]. Many nucleoside
analogs with modifications on the heterocyclic bases have
been investigated for their antiviral and anticancer
activities [3]. Purine scaffolds, such as (R)-Roscovition
have been shown to act as antitumor kinase inhibitors [4,5].
The first generation cyclin-dependent kinase inhibitors
have already entered clinical trials. A large number of
purine derivatives have been synthesized [6–8]. It has been
reported that these compounds have potential for targeted
nucleotide binding proteins that play a significant role in
many biological processes [9,10]. The dedifferentiation
agent “Reversine” [2-(4-morpholinoanilino)-N6-cyclohexy-
ladenine] was found to be a potent antagonist for the human
A3 adenosine receptor (AR) with a Ki value of 0.66 mM [11].
It has exhibited potential antitumor activity. However, the
solubility of purine derivatives has always been a problem.
Scientists have been trying to reduce the side effects of
the molecules and improve their biological activities. The
saccharide compounds have been one of the most important
types of drug. Glycoconjugates, formed after chemical
modification of the drug with the sugars and their deriva-
tives, are often able to effectively reduce the toxicity of
drugs and enhance the activity [12,13]. The synthesis of
2-substituted purines with aryl-glycosidic moiety has
not yet been reported.
RESULTS AND DISCUSSION
The synthesis of compounds 1–14 (Table 1) was
straightforward by utilizing 2,6-dichloropurine as the
starting material as shown in the titled scheme.
The intermediates 2-chloro-6-(cyclohexylamino)purine,
2-chloro-6-(n-butylamino)purine, and 2-chloro-6-(aryla-
mino)purine of compounds 1–14 can be easily obtained
by diisopropylethylamine or triethylamine catalyzed
nucleophilic substitution reaction between 2,6-dichloro-
purine and cyclohexylamine, n-butylamine or substituted
aniline reagents [14]. A series of target compounds 1–10
have been prepared from the reaction of the intermediates
and corresponding substituted anilines. For this type of
synthesis, the reaction conditions are quite harsh because
of the weak reactivity of the 2-position of purine base.
Some reaction procedures have been reported using
fivefold excess of aromatic amines in DMF solvent in at
© 2014 HeteroCorporation

474
H. Liu, L. Li, S. Qurat-ul-ain, and T. Jiang
Vol 52
Table 1
Structure of target compounds 1–14.
Comp.
X
Y
Yield (%)
76.4
1
2
3
4
86.4
85.4
61.2
5
89.7
87.7
88.2
80.1
56.6
80.3
6
7
8
9
10
11–14
82.3
45.3
81.0
54.3
11: R4 = H, R5 = OH, R6 = CH2OH
12: R4 = OH, R5 = H, R6 = CH2OH
14: R4 = H, R5 = OH, R6 = H
13: R4 = H, R5 =
, R6 = CH2OH
150ꢀC for 30 h [15]. However, high temperature leads to
the complex composition of the products. So, we decided
to explore acid catalysis to alleviate the problems. Our
decision was based on the rationale that the protonation
of either ring nitrogen N-3 or the 6-amino group would
make the six-membered ring electron-deficient that
facilitates the displacement of the 2-chloro substituent.
Catalytic amount (0.02 equiv) of aqueous hydrochloric
acid (37%) was added to the reaction mixture at 117ꢀC,
followed by addition of corresponding aromatic
amine (1.1 equiv). The reaction was completed in 12 h.
Hydrochloride salt was formed by the product 2,6-disub-
stituted purines, and one molecule hydrogen chloride
was taken off from the substitution reaction and isolated
from the reaction solution. After alkalization reaction
by triethylamine, compounds 1–10 were obtained in
56–89% yield.
Another group of target compounds, 2-(4-O-glyco-
phenylamino)-6-(cyclohexylamino)purine (11–14) were
synthesized analogously (Scheme 1). The p-amido-phenyl-
b-D-glucosides has been synthesized from acetobromo-
glucosides using tetrabutylammonium bromide as a
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Activity Evaluation of 2,6-Disubstituted Purine Derivatives
475
Scheme 1. Reagent and conditions: (i) p-nitrophenol, TBAB, NaOH, 45ꢀC, 12 h; (ii) H2, Pd/C(10%), EtOAc–MeOH, RT; (iii) 2-chloro-6-(cyclohexylamino)
purine (0.9equiv), n-BuOH, HCl (0.02equiv), reflux, 12h; and (iv) MeOH–MeONa, RT.
phase-transfer catalyst [16]. The monosacharides used
for glucosides synthesis are D-(+)-glucose, D-galactose,
D-lactose, and D-(+)-xylose. Compounds 11–14 were
obtained in 45–82% yields. All the compounds 1–14
high yields. Inhibition activity assay against liver cancer
cell lines of Bel-7402 and lung cancer cell lines of A549
have performed, in which the compounds 3 and 9 show
good activity with IC50 value of 13.02 and 27.76 mM,
whereas other compounds show moderate activity.
1
were characterized by HRMS, H-NMR, and 13C-NMR.
As can be seen from the reaction process, purine
derivatives of modified by glycosylation can be dissolved
at the reaction solution n-butyl alcohol. The products were
obtained with adding a certain amount ethyl acetate.
After deacetylation reaction, compounds 11–14 have
better solubilities.
EXPERIMENTAL
The chemicals, solvents for synthesis, and spectral grade
solvents were purchased from Aladdin (China) and used without
further purification. Melting points are uncorrected and were
determined automatically on an X-6 apparatus (Tech-Beijing).
1H-NMR spectra were recorded at 400 MHz on a Bruker
The synthesized compounds were evaluated preliminarily
for inhibition against lung cancer cell lines of A549 and liver
cancer cell lines of Bel-7402 on the basis of the MTT
method. First, compounds 1–4 were evaluated for inhibition
against lung cancer cell line of A549. Compound 3 exhibited
moderate inhibitory activity against A549 with half maximal
inhibitory concentration (IC50) value of 30.32. Then,
compound 3 was evaluated for inhibition against liver cancer
cell line of Bel-7402 with IC50 value of 13.02. The other
compounds were evaluated for inhibition against liver cancer
cell lines of Bel-7402. The calculated IC50 values for
compounds 1–14 are given in Table 2. The results show that
2-(4-benzyloxy-phenylamino)-6-(cyclohexylamino)purine
(3), 2-(4-chloro-phenylamino)-6-(n-butyl amino)purine (5),
2-(4-morpholinoamino)-6-(4-hydroxy-phenylamino) purine
(9), and 2-(4-O- galactosyl-phenylamino)-6-(cyclohexyla-
mino)purine (12) exhibited moderate inhibitory activity
against Bel-7402 cell line with IC50 value of 13.02, 40.80,
27.76, and 38.25, respectively.
Table 2
Half maximal inhibitory concentration (IC50) values of synthesized com-
pounds for cancer cells A549 or Bel-7402
Comp.
Cancer cells
IC50 (mM)
1
2
3
4
3
5
6
7
A549
A549
A549
>100
>100
30.32
>100
13.02
40.80
>100
>100
>100
27.76
>100
82.83
38.25
–
A549
Bel-7402
Bel-7402
Bel-7402
Bel-7402
Bel-7402
Bel-7402
Bel-7402
Bel-7402
Bel-7402
Bel-7402
Bel-7402
8
9
10
11
12
13
14
In summary, we have shown the synthesis of 2,6-disub-
stituted purine derivatives from 2,6-dichloropurine with
75.33
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DOI 10.1002/jhet

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H. Liu, L. Li, S. Qurat-ul-ain, and T. Jiang
Vol 52
spectrometer. Chemical shifts are expressed as d ppm units
(parts per million) using residual undeuterated solvent as
an internal reference. Coupling constants J are valued in
Hertz (Hz).
25.7. HRMS(m/z): Calcd for C17H20N6F + H+ 327.1728,
found 327.1724.
2-(4-Benzyloxy-phenylamino)-6-(cyclohexylamino)purine
(3).
Gray powder, 85.4% yield, mp 126.9–130.8ꢀC. 1H-
NMR (DMSO-d6): d 9.45 (bs, 1H, NH), 8.37 (s, 1H, CH),
7.48–6.93 (m, 9H, ArH), 5.05 (s, 2H, CH2O), 3.89 (bs, 1H,
NH), 1.92–1.17 (m, 11H, CH2CHN). 13C-NMR (DMSO-d6):
d 155.1, 137.7, 132.3, 132.2, 132.1, 128.9, 128.7, 128.4,
128.3, 128.1, 128.0, 122.8, 115.4, 69.9, 50.7, 32.4, 25.6,
24.9. HRMS(m/z): Calcd for C24H27ON6 + H+ 415.2241,
Typical procedure for the intermediates of compounds 1–
14 synthesis.
2-Chloro-6-(cyclohexylamino)purine, 2-chloro-
6-(n-butylamino)purine, and 2-chloro-6-(arylamino)purine have
been obtained in one step from 2,6-dichloropurine according
to Ref. [14]. 4-Morpholinyl-aniline was prepared according to
Ref. [17]. 4-Aminobenzene-O-acetyl-glucosides were synthesized
from acetobromo-glucosides (15a–d). The solution of
p-nitrophenol (3.75 mmol) dissolved in 1M sodium hydroxide
solution and 15a (or 15b, 15c, and 15d) (2.41 mmol) in
trichloromethane (5 mL) were added dropwise to the stirred
mixture of TBAB (0.05 g) in trichloromethane and water
(1:1). The resulted suspension was stirred at 45ꢀC for 12 h,
the organic layer was separated, and solvent was vacuum
evaporated. The residue was recrystallized in alcohol to
obtain 4-nitrobenzene-O-acetyl-glucosides in 45–72% yield.
4-Aminobenzene-O-acetyl-glucosides were prepared from 4-
nitrobenzene-O-acetyl-glucosides by metal catalyzed reduction
with hydrogen over 10% Pd/C in methanol and ethyl acetate
at RT.
Typical procedure for compounds 1–14 synthesis.
Corresponding arylamine (Y-NH2) dissolved in n-butyl alcohol
(5 mL) and hydrochloric acid were added to the stirred
solution of the intermediates 2-chloro-6-(cyclohexylamino)
purine [or 2-chloro-6-(n-butylamino)purine, 2-chloro-6-
(arylamino)purine] (2 mmol). The reaction mixture was
stirred and refluxed for 12 h under nitrogen, the formed
precipitate was filtered and washed with n-butyl alcohol
(5 mL) and ethyl ether (2 mL). The product was dispersed
with absolute methanol (2 mL). Triethylamine was dropped
in until the solid was dissolved completely. After stirring at
RT for 24 h, 5 mL of water was added. The resulting
precipitate was collected and washed with water (5 mL),
and compounds 1–10 were obtained.
found 415.2238.
2-(4-Methoxy-phenylamino)-6-(cyclohexylamino)purine
(4).
Gray powder, 61.2% yield, mp 123.7–126.9ꢀC. 1H-
NMR (DMSO-d6) : d 9.71 (bs, 1H, NH), 8.46 (s, 1H, CH),
7.49 (d, 2H, J = 8.4 Hz, ArH), 6.88 (d, 2H, J = 8.8 Hz,
ArH), 3.91 (bs, 1H, NH), 3.74 (s, 3H, OCH3), 1.93–1.31
(m, 11H, CH2CHN). 13C-NMR (DMSO-d6): d 157.1, 154.2,
153.8, 136.4, 135.8, 120.3, 114.0, 55.7, 49.1, 33.1, 25.9,
25.8. HRMS (m/z): Calcd for C18H23ON6 + H+ 339.1928,
found 339.1924.
2-(4-Chloro-phenylamino)-6-(n-butylamino)purine (5).
White powder, 89.7% yield, mp 203.3–206.6ꢀC. 1H-NMR
(DMSO-d6): d 9.86 (bs, 1H, NH), 8.73 (s, 1H, CH), 7.76
(d, 2H, J = 8.8 Hz, ArH), 7.35 (m, 2H, J = 6.8 Hz, ArH),
3.53–3.51 (m, 2H, CH2), 1.65–1.58 (m, 2H, CH2), 1.46–1.36
(m, 2H, CH2), 0.89 (t, 3H, J = 7.2 Hz, CH3). 13C-NMR
(DMSO-d6):
d 138.9, 128.9, 121.5, 31.0, 20.1, 14.1.
HRMS(m/z): Calcd for C15H18N6Cl + H+ 317.1276, found
317.1275.
2-(4-Fluoro-phenylamino)-6-(n-butylamino)purine (6).
White powder, 87.7% yield. 1H-NMR (DMSO-d6): d 9.79
(bs, 1H, NH), 8.63 (s, 1H, CH), 7.68 (m, 2H, J = 7.6 Hz,
ArH), 7.18 (m, 2H, J = 7.6 Hz, ArH), 3.49–3.46 (m, 2H,
CH2), 1.62–1.58 (m, 2H, CH2), 1.43–1.33 (m, 2H, CH2),
0.89 (t, 3H, J = 7.2 Hz, CH3). 13C-NMR (DMSO-d6): d
157.2, 122.4, 115.8, 115.6, 31.0, 20.1, 14.1. HRMS(m/z):
Calcd for C15H18N6Cl + H+ 301.1571, found 301.1565.
2-(4-Benzyloxy-phenylamino)-6-(n-butylamino)purine (7).
White powder, 88.2% yield. 1H-NMR (DMSO-d6): d 9.70
(bs, 1H, NH), 8.46 (s, 1H, CH), 7.74–7.31 (m, 7H, ArH),
7.02 (d, 2H, J = 8.8 Hz, ArH), 5.10 (s, 2H, CH2O), 3.51–3.49
(m, 2H, CH2), 1.64–1.57 (m, 2H, CH2), 1.43–1.34 (m, 2H,
CH2), 0.91 (t, 3H, J = 7.7 Hz, CH3). 13C-NMR (DMSO-d6) d:
154.3, 136.8, 131.2, 128.1, 127.4, 127.3, 122.2, 114.5, 69.0,
40.1, 30.2, 19.2, 13.2. HRMS (m/z): Calcd for
The solution of 4-aminobenzene-O-acetyl-glucosides in n-bu-
tyl alcohol (5 mL), hydrochloric acid, and 2-chloro-6-(cyclohexy-
lamino)purine (0.9 equiv) were mixed; after stirring and refluxing
the reaction mixture for 12 h under nitrogen, 20 mL ethyl acetate
was added. The formed precipitate was filtered and washed with
n-butyl alcohol (5 mL) and ethyl ether (2 mL). After de-O-acety-
lation with sodium methoxide, compounds 11–14 were obtained.
1
C22H25ON6 + H+ 389.2084, found 389.2074.
All the compounds of 1–14 were characterized by HRMS, H-
NMR, and 13C-NMR.
2-(4-Morpholinoamino)-6-(4-chloro-phenylamino)purine (8).
Gray powder, 80.3% yield, mp 279.3–283.9ꢀC. 1H-NMR
(DMSO-d6): d 10.5 (s, 1H, HN), 10.7 (s, 1H, HN), 8.39
(s, 1H, CH), 7.93–7.89 (m, 2H, ArH), 7.48–7.39 (m, 2H, ArH),
7.20 (d, 2H, J = 8.8 Hz, ArH), 7.04 (d, 2H, J = 8.8 Hz, ArH),
3.16–3.12 (m, 4H, CH2NCH2), 3.80–3.74 (m, 4H, CH2OCH2).
13C-NMR (DMSO-d6): d 152.8, 152.3, 149.6, 140.9, 137.3,
128.2, 126.7, 123.9, 123.2, 122.4, 121.3, 116.1, 113.4, 65.2,
48.5. HRMS (m/z): Calcd for C21H21ON7Cl + H+ 422.1491,
2-(4-Chloro-phenylamino)-6-(cyclohexylamino)purine (1).
Gray powder, 76.4% yield, mp 178.6–181.4ꢀC. 1H-NMR
(DMSO-d6): d 9.85 (bs, 1H, NH), 8.75 (s, 1H, CH), 7.76
(d, 2H, J = 8.8 Hz, ArH), 7.38 (d, 2H, J = 8.8 Hz, ArH),
4.03 (bs, 1H, NH), 1.99–1.24 (m, 11H, CH2CHN). 13C-NMR
(DMSO-d6):
d
156.4, 154.2, 151.2, 141.5, 136.8,
128.5,128.5, 123.7, 119.9, 114.6, 49.4, 33.1, 25.9, 25.7.
HRMS(m/z): Calcd for C17H20N6Cl + H+ 343.1432, found
343.1433.
found 422.1481.
2-(4-Fluoro-phenylamino)-6-(cyclohexylamino)purine (2).
2-(4-Morpholinoamino)-6-(4-hydroxy-phenylamino)purine
Gray powder, 86.4% yield, mp 115.7–117.9ꢀC. 1H-NMR
(DMSO-d6): d 12.40 (bs, 1H, NH), 8.87 (s, 1H, CH), 7.85
(d, 2H, J = 8.2 Hz, ArH), 7.06 (d, 2H, J = 8.7 Hz, ArH), 4.06
(bs, 1H, NH), 1.92–1.76 (m, 5H, CH2CH—N), 1.36–1.18
(m, 6H, CH2). 13C-NMR (DMSO-d6): d 157.6, 156.7, 156.1,
151.3, 138.9, 136.6, 119.9, 115.2, 115.0, 49.2, 33.1, 25.8,
(9).
White powder, 56.6% yield, mp > 300ꢀC. 1H-NMR
(DMSO-d6): d 10.9 (s, 1H, HN), 9.70 (s, 1H, HN), 8.78 (s,
1H, CH), 7.64–7.62 (m, 2H, ArH), 7.23 (d, 2H, J = 8.8 Hz,
ArH), 7.06 (d, 2H, J = 8.8 Hz, ArH), 6.78 (d, 2H, J = 8.8 Hz,
ArH), 3.78–3.73 (d, 4H, CH2OCH2), 3.17–3.12 (d, 4H,
CH2NCH2). 13C-NMR (DMSO-d6): d 153.9, 148.3, 129.2,
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Activity Evaluation of 2,6-Disubstituted Purine Derivatives
477
123.1, 122.1, 121.0, 115.7, 114.9, 104.8, 65.3, 64.1, 48.3.
(m, 1H), 3.77 (s, 1H), 3.76 (s, 1H), 1.98–1.33 (m, 11H,
HRMS(m/z): Calcd for C21H22O2N7 + H+ 404.1829, found
CH2CHN). 13C-NMR (DMSO-d6):
d 152.8, 152.1, 139.2,
404.1825.
134.9, 121.3, 117.1, 102.1, 77.1, 73.7, 70.0, 66.2, 50.2, 32.6,
25.7, 25.2, 19.1. HRMS (m/z): Calcd for C22H29O5N6 + H+
457.2194, found 457.2188.
2-(4-Morpholinoanilino)-6-(4-fluoro-phenylamino)purine (10).
Gray powder, mp > 300ꢀC. 1H-NMR (DMSO-d6): d 10.4
(s, 1H, HN), 8.34 (s, 1H, CH), 7.87–7.04 (m, 8H, ArH),
3.84–3.74 (m, 4H, CH2OCH2), 3.12–3.08 (m, 4H,
CH2NCH2). 13C-NMR (DMSO-d6): d 158.6, 157.1, 153.0,
152.0, 150.6, 140.9, 143.9, 123.2, 122.1, 115.6, 115.0,
114.83, 65.5, 48.1. HRMS (m/z) Calcd for C21H21ON7F + H+
Acknowledgments. The authors greatly appreciate the financial
support by the National Key Project of the Ministry of
International Cooperation (No. 2009DFA32080).
406.1786, found 406.1784.
2-(4-O-Glucosyl-phenylamino)-6-(cyclohexylamino)purine (11).
Brown powder, 82.3% yield, mp 232.0–234.1ꢀC. 1H-NMR
(DMSO-d6): d 8.59 (s, 1H, NH), 7.77 ( s, 1H, CH), 7.72–6.91
(m, 4H, ArH), 4.73 (d, 1H, J = 7.8 Hz, CH—O), 4.63 (s, 1H),
4.04 (s, 1H), 3.70–3.17 (m, 6H, —OH), 1.94–1.14 (m, 11H,
CH2CHN). 13C-NMR (DMSO-d6): d 156.9, 151.8, 137.1,
119.7, 119.6, 116.9, 116.8, 101.9, 101.9, 77.6, 77.2, 73.9, 70.4,
61.3, 49.3, 32.2, 25.9, 25.7. HRMS (m/z): Calcd for
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C23H31O6N6 + H+ 487.2300, found 487.2292.
2-(4-O-Galactosyl-phenylamino)-6-(cyclohexylamino)purine (12).
Brown powder, 45.3% yield, mp 178.2–181.9ꢀC. 1H-NMR
(DMSO-d6) : d 9.85 (bs, 1H, NH), 9.15 (bs, 1H, NH), 8.51
(s, 1H, CH), 7.55–7.03 (m, 4H, ArH), 4.79 (s, 1H), 3.72–3.56
(m, 10H), 1.99–1.06 (m, 11H, CH2CHN). 13C-NMR (DMSO-d6):
d 154.2, 150.9, 133.0, 122.6, 117.0, 101.9, 75.9, 73.8, 70.9, 68.6,
60.5, 50.7, 35.2, 32.4, 25.6, 24.9, 19.2, 19.1, 14.4. HRMS (m/z):
Calcd for C23H31O6N6 + H+ 487.2300, found 487.2286.
2-(4-O-Lactosyl-phenylamino)-6-(cyclohexylamino)purine (13).
Brown powder, 81.0% yield, mp190.3–194.7ꢀC. 1H-NMR
(DMSO-d6): d 9.87 (bs, 1H, NH), 9.15 (bs, 1H, NH), 8.53
(s, 1H, CH), 7.57–7.05 (m, 4H, ArH), 4.95 (s, 2H), 4.28
(s, 2H), 3.67–3.37 (m, 14H), 1.99–1.06 (m, 11H, CH2CHN).
13C-NMR (DMSO-d6): d 153.9, 150.9, 148.5, 133.2, 125.0,
122.5, 117.7, 117.0, 105.8, 104.3, 100.8, 80.7, 76.1, 75.5,
75.4, 73.8, 73.5, 71.2, 68.7, 60.9, 60.6, 56.6, 50.8, 35.2, 32.4,
25.6, 24.9, 19.2, 19.1, 14.4. HRMS (m/z): Calcd for
C29H41O11N6 + H+ 649.2828, found 649.2831.
2-(4-O-Xylosyl-phenylamino)-6-(cyclohexylamino) (14).
Brown powder, 54.3% yield. 1H-NMR (DMSO-d6): d 9.56
(bs, 1H), 8.21 (s, 1H, CH), 7.62 (d, 2H, J = 8.8 Hz, ArH), 6.97
(d, 2H, J = 8.8 Hz, ArH), 5.40 (s, 1H), 5.16 (s, 2H), 4.82–4.81
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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