Synthesis and antimalarial-activity evaluation of tetraoxane-triazine hybrids and spiro[piperidine-4,3′-tetraoxanes]

Article abstract of DOI:10.1002/hlca.201200015

A series of tetraoxane-triazine hybrids and spiro[piperidine-4,3′- tetraoxanes] have been synthesized, and all the compounds were screened for in vitro antimalarial activity against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plas

Full text of DOI:10.1002/hlca.201200015

Helvetica Chimica Acta – Vol. 95 (2012)
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Synthesis and Antimalarial-Activity Evaluation of TetraoxaneꢀTriazine
Hybrids and Spiro[piperidine-4,3’-tetraoxanes]
by Nitin Kumara), Shabana I. Khanb), and Diwan S. Rawat*a)
a) Department of Chemistry, University of Delhi, Delhi-110007, India
(e-mail: dsrawat@chemistry.du.ac.in)
b) National Centre for Natural Products Research, School of Pharmacy, University of Mississippi,
MS-38677, USA
A series of tetraoxaneꢀtriazine hybrids and spiro[piperidine-4,3’-tetraoxanes] have been synthe-
sized, and all the compounds were screened for in vitro antimalarial activity against chloroquine-sensitive
(D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum. Most of the spiro[piperidine-
4,3’-tetraoxanes] exhibited moderate to good antimalarial activities, and two compounds have shown
good antimalarial activity with IC50 values in the range of 0.30 to 0.70 mm against both the strains with
high selectivity index and no cytotoxicity towards mammalian kidney cell line.
Introduction. – Artemisinin (1) and its semi-synthetic derivatives such as
artemether, arteether, and artisunate belong to the endoperoxide class of compounds,
and these compounds have been used for the treatment of P. falciparum-related
infections where traditional antimalarial remedies such as chloroquine and mefloquine
have lost their efficacy [1]. Mechanistic studies revealed that the presence of a peroxide
bridge is essential for the activity of these compounds [2 – 5], and this key structural
feature led to the quest to discover other synthetically accessible peroxides as potential
antimalarial agents [3][4]. The subsequent studies identified tetraoxanes, 2, as a new
class of antimalarials, and some of these compounds have shown very promising
activities [6 – 11] (Fig. 1). These compounds such as artemisinin exert their activity due
to their ability to form radical species under physiological conditions and thus stop the
hemozoin formation [12]. Recent studies confirmed that introduction of a basic moiety
in the trioxane and tetraoxane pharmacophore can improve the antimalarial activity of
these compounds [13][14].
Fig. 1. Endoperoxide-based antimalarials
The dihydrofolate reductase (DHFR) is another target that has been subject of
intense study in malaria research, and substituted s-triazine derivatives have been
ꢀ 2012 Verlag Helvetica Chimica Acta AG, Zꢁrich

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widely studied against DHFR. This class of compounds also possess a broad range of
biological activities such as antitumor, anticancer, cytotoxicity, anti-inflammatory,
antibacterial, antifungal, antimalarial, antitrypanosomal, anti-AIDS, etc., and played an
important role in the development of medicinal chemistry [15 – 20]. All the biologically
active s-triazine derivatives are obtained from commercially available, inexpensive
reagents such as melamine, cyanuric chloride, and cyanuric acid. Cycloguanil (3), a
triazine-based antimalarial drug and a metabolite of the antimalarial drug chlorogua-
nide (4), inhibits dihydrofolate reductase (DHFR) domain of P. falciparum and P.
berghei [21 – 30] (Fig. 2). Inhibition of cellular DHFR reduces the source of
tetrahydrofolates, which eventually leads to cell death as a result of deficient DNA
biosynthesis. Cycloguanil also affects proliferating human blood mononuclear cells
when studied in vitro [31], and has a potent inhibitory effect on Toxoplasma gondii
when combined with a non-inhibitory concentration of sulfadiazine [28].
Fig. 2. Dihydrofolate reductase inhibitors
To overcome the drug resistance, the concept of hybrid molecules has been
introduced recently, and some of these hybrids have entered the clinical trials [32]. As a
part of ongoing work towards the development of novel antimalarials [33 – 36], we
report herein synthesis and antimalarial activity of tetraoxaneꢀtriazine conjugates and
spiro[piperidine-4,3’-tetraoxanes].
Results and Discussion. – Chemistry. Keeping in mind the numerous biological
applications of triazine derivatives and antimalarial activities of tetraoxanes, we
designed tetraoxaneꢀtriazine conjugates 12a – 12i, 13a – 13i, in anticipation that this
kind of hybrid molecules may exhibit better antimalarial activity, and may solve the
problem of drug resistance, as these hybrids contain two different antimalarially active
pharmacophores with different targets. We initiated our work by synthesizing the
known compounds 6a and 6b using cyanuric chloride (5) as a starting material
(Scheme 1) [37 – 40]. It is important to mention here that 5 at 08 with aliphatic amines/
aromatic amines undergoes nucleophilic substitution reactions to give monoamino-
triazines in high and diamino-triazines in low yield. The second Cl-atom of
monoamino-triazines undergoes nucleophilic substitution reactions with aliphatic
amines/aromatic amines at room temperature to give diamino-triazines as major
products while triamino-triazines are formed in low yield. The Cl-atom of diamino-
triazines undergoes nucleophilic substitution reactions with substituted amines at
higher temperature. The reaction of 1 mol of amine with compound 5 at 08 in the
presence of anhydrous K2CO3 led to the formation of compounds 6a and 6b in
moderate-to-good yields (Scheme 1). Subsequent reaction of 1 mol of amine with
compounds 6a and 6b at room temperature in the presence of anhydrous K2CO3 gave

Helvetica Chimica Acta – Vol. 95 (2012)
1183
Scheme 1
a) RX, K2CO3, THF, 08, 3 h. b) R1X, K2CO3, THF, 3 h, room temperature, with 6a. c) R1X, K2CO3, THF,
3 h, room temperature, with 6b. d) Ethylenediamine, K2CO3, THF, 608, 3 h.
compounds 7a – 7i and 8a – 8i, respectively, in moderate-to-good yields (Scheme 1). The
third nucleophilic reaction was carried out by reacting compounds 7a – 7i and 8a – 8i,
respectively, with excess of ethylenediamine in the presence of K2CO3 in THF at 608.
After usual workup and purification, all the synthesized compounds 9a – 9i and 10a – 10i
were characterized spectroscopically. Finally, compounds 9a – 9i and 10a – 10i were
reacted with compound 11 [33] in the presence of Et3N and ClCOOEt in THF at room
temperature for 2 h to give compounds 12a – 12i and 13a – 13i, respectively, in good-to-
moderate yields (Scheme 2).
The spiro[piperidine-4,3’-tetraoxanes] were prepared in anticipation that the N-
atom of the piperidinone ring will help the tetraoxane to accumulate more in the acidic
food vacuole of the parasite, and, thus, these compounds will exhibit improved
antimalarial activities. With these aims in mind, we started our synthesis with the
preparation of compounds 15a and 15b [41][42] as outlined in Scheme 3. Reaction of
15a and 15b with different substituted ketones/aldehydes in presence of 1,1,1,3,3,3-
hexafluoropropan-2-ol (HFIP), methyltrioxorhenium (MTO), and an Et2O solution of
HBF4 led to the formation of desired the compounds 16a – 16m and 17a – 17h,
respectively in moderate yields (Scheme 3) [43].
Biological Activity. In vitro Antimalarial Activity. All the synthesized compounds,
12a – 12i and 13a – 13i, were screened for antimalarial activity against D6 (chloroquine-

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Scheme 2
sensitive) and W2 (chloroquine-resistant) strains of P. falciparum, and for cytotoxicity
towards mammalian kidney cells (Vero cells) up to a highest concentration of 12.5 mm
in an in vitro assay. Chloroquine and artemisinin were used as standard drugs for
antimalarial activity, and doxorubicin was used as standard drug for cytotoxicity. The in
vitro antimalarial activity was determined on the basis of plasmodial LDH activity as an
index of plasmodial growth [44] and expressed as IC50 values. Selectivity index (SI) of
antimalarial activity was calculated based on the cytotoxicity to mammalian cells. Most
of the compounds were inactive except compounds 12b, 12e, and 12i. These compounds
exhibited moderate antimalarial activities with IC50 values in the range of 2.74 – 5.45
(D6) and 2.13 – 5.43 mm (W2) (Table).
Some spiro[piperidine-4,3’-tetraoxanes] have shown very good-to-moderate anti-
malarial activities. Two compounds, 16a (R1 ¼ 4-MeꢀC6H9) and 17a (R1 ¼ 4-
MeꢀC6H4), exhibited good activities against both strains of P. falciparum with IC50
values in the range of 0.30 – 0.70 (D6) and 0.20 – 0.83 mm (W2) with high SIs.
Compounds 16b, 16c, 17c, and 17h with (R1 ¼ Ph, 4-MeꢀC6H4, 2-MeꢀC6H4, 4-
MeOꢀC6H4, resp.) exhibited moderate-to-good antimalarial activities with IC50 values
in the range of 1.48 – 4.90 (D6) and 1.40 – 7.36 mm (W2). All other compounds were
found to be inactive up to tested concentration (25 mm) with no clear SAR.
Conclusions. – We have successfully synthesized two new series of substituted
triazineꢀtetraoxane hybrids and spiro[piperidine-4,3’-tetraoxanes]. Some of the

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Scheme 3
a) TsCl or benzenesulfonyl chloride, K2CO3, CHCl3/H2O 1:1, 4 h, r.t. b) Aldehyde/ketone, H2O2, HBF4 ·
Et2O, 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP), methyltrioxorhenium (MeReO3, MTO), 2 h, room
temperature, with 15a. c) Aldehyde/ketone, H2O2, HBF4 · Et2O, 1,1,1,3,3,3-hexafluoropropan-2-ol
(HFIP), methyltrioxorhenium (MTO), 2 h, room temperature, with 15b.
Table. In vitro Antimalarial Activities of TetraoxaneꢀTriazine Hybrid and Spiro[piperidine-4,3’-
tetraoxanes]
Compound
P. f a) (D6) [mm]
SIb)
> 1.5
> 1.5
> 2.6
P. f (W2) [mm]
SI
> 1.5
Cytotoxicity (Vero cell)
12b
12e
12i
16a
16b
16c
17a
17c
5.43
5.23
2.74
0.70
1.51
2.09
0.30
1.48
4.90
0.035
0.015
5.43
3.76
2.13
0.83
1.40
1.89
> 0.20
1.71
7.36
0.22
NCc)
NC
NC
NC
NC
NC
NC
NC
NC
NC
NC
> 2.1
> 3.4
> 14.4
> 9.0
> 6.2
> 59.5
> 7.1
> 1.6
> 17
> 8.4
> 5.6
> 39.7
> 8.2
> 2.4
17h
Chloroquine
Artemisinin
0.013
a) P. f ¼ Plasmodium falciparum.b) SI ¼ Selectivity index. c) NC ¼ No cytotoxicity.

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compounds have shown promising in vitro antimalarial activities without showing any
cytotoxicity against Vero cells. Out of 56 compounds under study, two compounds, 16a
and 17a, have shown good activities against both strains of P. falciparum with high SI.
Further derivatization of the most active analogs is under progress, and results will be
published in due course.
D.S.R. thanks the Department of Science and Technology (SR/S1/OC-08/2008), New Delhi, India, for
financial support, and USIC-CIF, University of Delhi for NMR data. N. K. is thankful to CSIR, New
Delhi, for the award of junior and senior research fellowships. United States Department of Agriculture
(USDA), Agricultural Research Service Specific Cooperative Agreement No. 58-6408-2-0009, is also
acknowledged for partial support of this work. Mr. John Trott is acknowledged for his excellent technical
assistance in the screening of biological activity at NCNPR, University of Mississippi, USA.
Experimental Part
General. All chemicals used in the syntheses were purchased from SigmaꢀAldrich and were used as
such. TLC was used to monitor the progress of the reactions. The compounds were purified by silica-gel
column chromatography (CC; SiO2; Merck, India). M.p.: melting-point apparatus SRS EZ 120;
uncorrected. IR Spectra (KBr, film): Perkin-Elmer FT-IR spectrophotometer and the values are
expressed as nmax in cmꢀ1. 1H-NMR Spectra: Bruker 320 Spectrospin spectrometer at 300 MHz and Jeol
spectospin ECX400 at 400 MHz.13C-NMR Spectra: 75.5 and 100 MHz, resp., with TMS as internal
standard; the chemical-shift values on d scale [ppm] and the coupling constants (J) in Hz. MS: Waters
micro mass LCT mass spectrometer/data system. Elemental analyses: Carlo Erba Model EA-1108
elemental analyzer, and data of C, H, and N are within ꢁ 0.4% of calculated values.
Synthesis and Characterization of the Compounds. Synthesis of 6a and 6b [37 – 40]. 2,4-Dichloro-6-
(morpholin-4-yl)-1,3,5-triazine (6a). Yield: 75.3%. M.p. 1668. IR (KBr): 3110, 2970, 2861, 1922, 1585,
1479, 1232, 992. 1H-NMR (400 MHz, CDCl3): 3.68 (t, J ¼ 5.1, 2 NCH2CH2O); 3.82 (t, J ¼ 5.1, 2
NCH2CH2O).13C-NMR (100 MHz, CDCl3): 44.3; 66.2; 163.8; 170.2. ESI-MS: 235.1 (100, [M þ H]þ),
237.1 (63).
2,4-Dichloro-6-(4-phenylpiperazin-1-yl)-1,3,5-triazine (6b). Yield: 76%. M.p. 1658. IR (film): 2902,
1
2818, 1599, 1569, 1494, 1445, 1312, 1255, 1230, 1003, 980, 912, 758. H-NMR (400 MHz, CDCl3): 3.19 –
3.25 (m, 2 NCH2CH2NPh); 3.95 – 3.98 (m, 2 NCH2CH2NPh); 6.88 – 6.98 (m, 3 arom. H); 7.27 – 7.31 (m,
2 arom. H). 13C-NMR (100 MHz, CDCl3): 43.4; 49.3; 116.7; 120.5; 129.2; 157.0; 164.3; 169.7. ESI-MS:
310.0 (100, [M þ H]þ), 312.2 (64).
General Procedure for the Synthesis of 7b – 7i and 8a – 8i, Examplified by the Preparation of 4,4’-(6-
Chloro-1,3,5-triazine-2,4-diyl)dimorpholine (¼2-Chloro-4,6-di(morpholin-4-yl)-1,3,5-triazine; 7a). Mor-
pholine (1.85 g, 21.2 mmol) was added to a suspension of 6a (5 g, 21.2 mmol) in THF (30 ml) at r.t.,
followed by K2CO3 (8.80 g, 63.8 mmol). The mixture was stirred at r.t. for 3 – 4 h. Then, the mixture was
filtered to remove K2CO3, and excess of solvent was evaporated under vacuum. The residue thus
obtained was dissolved in 30 ml of CHCl3 and washed with sat. brine. The CHCl3 layer was dried
(Na2SO4), and excess of solvent was removed under vacuum to give crude product, which was purified by
CC (SiO2; AcOEt/hexane) to yield 7a (4.12 g, 68%). White solid. M.p. 1758 ([45]: 1738). IR (film): 2979,
2966, 2852, 1604, 1567, 1493, 1448, 1361, 1305, 1269, 1206, 1181, 1117, 1062, 977, 955, 797. 1H-NMR
(400 MHz, CDCl3): 3.65 – 3.68 (m, 4 – NCH2CH2O); 3.70 – 3.81 (m, 4 NCH2CH2O). 13C-NMR (100 MHz,
CDCl3): 43.8; 66.6; 164.4; 169.6. ESI-MS: 286.7 (100, [M þ H]þ), 288.8 (32).
2-Chloro-4-(morpholin-4-yl)-6-(piperidin-1-yl)-1,3,5-triazine (7b). Yield: 68%. M.p. 1458 ([46]:
140 – 1428). IR (film): 2935, 2855, 1567, 1493, 1445, 1309, 1237, 1116, 975, 799. 1H-NMR (400 MHz,
CDCl3): 1.54 – 1.57 (m, 4 H), 1.64 – 1.65 (m, 2 H); 3.58 – 3.88 (m, 12 H).13C-NMR (100 MHz, CDCl3):
24.6; 25.8; 43.8; 44.6; 66.6; 164.5; 169.5. ESI-MS: 284.1 (100, [M þ H]þ), 286.2 (31).
4-Chloro-N-cyclohexyl-6-(morpholin-4-yl)-1,3,5-triazin-2-amine (7c). Yield: 62%. M.p. 1938. IR
(film): 3347 (NH), 2923, 2852, 1583, 1537, 1503, 1441, 1247, 989, 792. 1H-NMR (400 MHz, CDCl3): 1.09 –
1.46 (m, 4 H); 1.56 – 1.76 (m, 6 H); 1.89 – 2.03 (m, 2 H); 3.63 – 3.89 (m, 8 H).13C-NMR (100 MHz,

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CDCl3): 24.5; 25.5; 32.5; 32.2; 43.7; 49.2; 49.5; 66.6; 164.6; 169.1. ESI-MS: 298.1 (100, [M þ H]þ), 300.2
(32).
2-Chloro-4-(morpholin-4-yl)-6-(4-phenylpiperazin-1-yl)-1,3,5-triazine (7d). Yield: 58%. M.p. 1338.
IR (film): 2963, 2856, 1567, 1494, 1444, 1309, 1231, 1115, 1004, 978, 798. 1H-NMR (400 MHz, CDCl3): 3.19
(t, J ¼ 5.0, 2 NCH2CH2NPh); 3.71 – 3.72 (m, 2 NCH2CH2NPh); 3.79 – 3.80 (m, 2 NCH2CH2O); 3.86 – 3.94
(m, 2 NCH2CH2O); 6.88 – 6.95 (m, 3 arom. H); 7.25 – 7.30 (m, 2 arom. H).13C-NMR (100 MHz, CDCl3):
43.3; 43.8; 49.5; 66.5; 66.7; 116.6; 120.5; 129.2; 151.0; 164.3; 169.6. ESI-MS: 361.2 (100, [M þ H]þ), 363.2
(32).
4-Chloro-N-(4-methylphenyl)-6-(morpholin-4-yl)-1,3,5-triazin-2-amine (7e). Yield: 61%. M.p. 2128
([47]: 205 – 2078). IR (film): 3277 (NH), 2924, 1560, 1530, 1491, 1442, 1278, 1110, 979, 794, 731. 1H-NMR
(400 MHz, CDCl3): 2.32 (s, MeꢀC6H4); 3.68 – 3.75 (m, 2 NCH2CH2O); 3.76 – 3.82 (m, 2 NCH2CH2O);
7.08 (br. s, NH); 7.12 (d, J ¼ 7.8, 2 arom. H); 7.35 (d, J ¼ 7.8, 2 arom. H). 13C-NMR (100 MHz, CDCl3):
20.8; 44.0; 66.5; 120.7; 129.4; 133.7; 135.0; 165.5; 169.2. ESI-MS: 306.1 (100, [M þ H]þ), 308.1 (34).
4-Chloro-N-(2-methylphenyl)-6-(morpholin-4-yl)-1,3,5-triazin-2-amine (7f). Yield: 59%. M.p. 1518
([47]: 146 – 1508). IR (film): 3234 (NH), 2966, 2857, 1573, 1526, 1497, 1242, 1115, 981, 754, 730. 1H-NMR
(400 MHz, CDCl3): 2.28 (s, MeꢀC6H4); 3.61 – 3.88 (m, 2 NCH2CH2O); 6.88 (br. s, NH); 7.06 – 7.10 (m, 2
arom. H); 7.19 – 7.27 (m, 2 arom. H). ESI-MS: 306.1 (100, [M þ H]þ), 308.2 (34).
4-Chloro-6-(morpholin-4-yl)-N-[4-(propan-2-yl)phenyl]-1,3,5-triazin-2-amine (7g). Yield: 60%.
M.p. 1578. IR (film): 3283 (NH), 2961, 2863, 1576, 1530, 1514, 1422, 1248, 1115, 981, 732. 1H-NMR
(400 MHz, CDCl3): 1.22 (d, J ¼ 6.8, Me2CH); 2.85 – 2.90 (m, Me2CH); 3.68 – 3.78 (m, 2 NCH2CH2O);
3.79 – 3.89 (m, 2 NCH2CH2O); 7.18 (d, J ¼ 8.4, 2 arom. H); 7.25 (br. s, NH); 7.40 (d, J ¼ 8.4, 2 arom. H).
ESI-MS: 334.1 (100, [M þ H]þ), 336.2 (30).
4-Chloro-N-(4-methoxyphenyl)-6-(morpholin-4-yl)-1,3,5-triazin-2-amine (7h). Yield: 68%. M.p.
1538 ([47]: 146 – 1508). IR (film): 3285 (NH), 2921, 1579, 1532, 1510, 1422, 1243, 1114, 1033, 981, 798.
1H-NMR (400 MHz, CDCl3): 3.70 – 3.74 (m, 2 NCH2CH2O); 3.82 (s, MeO); 3.83 – 3.88 (m, 2
NCH2CH2O); 6.85 (d, J ¼ 6.8, 2 arom. H); 7.35 (d, J ¼ 6.8, 2 arom. H); 7.04 – 7.18 (br. s, NH).
13C-NMR (100 MHz, CDCl3): 44.0; 55.5; 66.5; 114.1; 122.6; 130.5; 156.4; 164.0; 164.5. ESI-MS: 322.1
(100, [M þ H]þ), 324.2 (31).
4-Chloro-N-(3,5-dimethoxyphenyl)-6-(morpholin-4-yl)-1,3,5-triazin-2-amine (7i). Yield: 67%. M.p.
1688. IR (film): 3323 (NH), 2934, 2862, 1587, 1530, 1461, 1207, 1155, 1061, 824, 797, 671. 1H-NMR
(300 MHz, CDCl3): 3.72 – 3.75 (m, 2 NCH2CH2O); 3.78 (s, 2 MeO); 3.82 – 3.86 (m, 2 NCH2CH2O); 6.22 –
6.24 (m, 1 arom. H); 6.74 ꢀ 6.75 (m, 2 arom. H); 7.17 (br. s, NH). 13C-NMR (75.5 MHz, CDCl3): 44.0;
55.2; 66.4; 95.9; 98.9; 138.8; 160.8; 163.7; 164.5; 169.3. ESI-MS: 352.1 (100, [M þ H]þ), 354.2 (33).
2-Chloro-4-(4-phenylpiperazin-1-yl)-6-(piperidin-1-yl)-1,3,5-triazine (8a). Yield: 57%. M.p. 1488. IR
1
(film): 2929, 2854, 1573, 1529, 1494, 1227, 987, 732. H-NMR (400 MHz, CDCl3): 1.09 – 1.37 (m, 3 H);
1.38 – 1.47 (m, 2 H); 1.55 – 1.78 (m, 3 H); 1.92 – 2.04 (m, 2 H); 3.13 – 3.29 (m, 2 NCH2CH2NPh); 3.78 – 3.97
(m, 2 NCH2CH2NPh); 6.88 – 6.95 (m, 3 arom. H); 7.26 – 7.30 (m, 2 arom. H). 13C-NMR (100 MHz,
CDCl3): 24.6; 25.5; 32.5; 33.2; 43.3; 49.2; 116.6; 120.4; 129.2; 151.0; 164.5; 169.6; 169.0. ESI-MS: 359.2
(100, [M þ H]þ), 361.2 (32).
4-Chloro-N-cyclohexyl-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-amine (8b). Yield: 53%. M.p. 958.
IR (nujol): 3296, 2923, 2854, 1505, 1416, 1383, 1300, 1283, 1227, 1155, 1010, 921, 806, 761. 1H-NMR
(400 MHz, CDCl3): 1.54 – 1.66 (m, 7 H); 3.18 – 3.20 (m, 4 H); 3.73 – 3.76 (m, 2 NCH2CH2NPh); 3.93 – 3.94
(m, 2 NCH2CH2NPh); 6.87 – 6.95 (m, 2 arom. H); 7.25 – 7.30 (m, 3 arom. H, NH). ESI-MS: 373.2 (100,
[M þ H]þ), 375.1 (31).
2-Chloro-4,6-bis(4-phenylpiperazin-1-yl)-1,3,5-triazine (8c). Yield: 49%. M.p. 1958. IR (film): 3059,
1
2963, 2902, 2818, 1569, 1445, 1312, 1255, 1230, 1194, 1153, 1045, 980, 912. H-NMR (400 MHz, CDCl3):
3.19 – 3.25 (m, 4 NCH2CH2NPh); 3.95 – 3.98 (m, 4 NCH2CH2NPh); 6.88 – 6.98 (m, 6 arom. H); 7.27 – 7.31
(m, 4 arom. H). ESI-MS: 436.2 (100, [M þ H]þ), 438.2 (33).
4-Chloro-N-(4-methylphenyl)-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-amine (8d). Yield: 48%.
M.p. 1028. IR (film): 3249 (NH), 2920, 2851, 1577, 1512, 1493, 1445, 1229, 980, 730. 1H-NMR
(400 MHz, CDCl3): 2.33 (s, MeꢀC6H4); 3.23 – 3.24 (m,
2 NCH2CH2NPh); 3.95 – 4.10 (m, 2
NCH2CH2NPh); 6.91 – 7.04 (m, 3 arom. H); 7.14 – 7.16 (d, J ¼ 8.2, 2 arom. H); 7.27 – 7.31 (m, 2 arom.
H, NH); 7.38 (d, J ¼ 8.2, 2 arom. H). ESI-MS: 381.2 (100, [M þ H]þ), 383.2 (33).

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4-Chloro-N-(2-methylphenyl)-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-amine (8e). Yield: 51%.
M.p. 1438. IR (film): 3391 (NH), 2922, 2381, 2207, 1620, 1574, 1494, 1232, 906, 755, 731. 1H-NMR
(400 MHz, CDCl3): 2.36 (s, MeꢀC6H4); 3.19 – 3.45 (m,
2 NCH2CH2NPh); 3.91 – 4.40 (m, 2
NCH2CH2NPh); 6.92 – 7.12 (m, 2 arom. H); 7.16 – 7.26 (m, 4 arom. H); 7.28 – 7.58 (m, 4 arom. H). ESI-
MS: 381.1 (100, [M þ H]þ), 383.1 (32).
4-Chloro-N-(4-ethylphenyl)-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-amine (8f). Yield: 48%. M.p.
1378. IR (film): 3271 (NH), 2964, 2927, 1574, 1514, 1230, 982, 912, 743. 1H-NMR (400 MHz, CDCl3): 1.21
(t, J ¼ 7.5, MeCH2); 2.60 – 2.64 (q, J ¼ 7.5, MeCH2); 3.15 – 3.26 (m, 2 NCH2CH2NPh); 3.91 – 4.05 (m, 2
NCH2CH2NPh); 6.90 – 6.96 (m, 3 arom. H); 7.05 (br. s, NH); 7.15 – 7.19 (m, 2 arom. H); 7.28 ꢀ 7.30 (m, 2
arom. H); 7.41 – 7.45 (m, 2 arom. H). ESI-MS: 395.2 (100, [M þ H]þ), 397.2 (32).
4-Chloro-6-(4-phenylpiperazin-1-yl)-N-[4-(propan-2-yl)phenyl]-1,3,5-triazin-2-amine (8g). Yield:
1
53%. M.p. 1978. IR (film): 3279 (NH), 2959, 1576, 1513, 1492, 1421, 1232, 980. H-NMR (300 MHz,
CDCl3): 1.25 (d, J ¼ 6.0, Me2CH); 2.88 – 2.92 (sept., J ¼ 4.0, Me2CH); 3.31 – 3.42 (m, 2 NCH2CH2NPh);
4.15 – 4.39 (m, 2 NCH2CH2NPh); 7.21 – 7.23 (m, 4 arom. H); 7.38 – 7.43 (m, 5 arom. H, NH). ESI-MS:
409.2 (100, [M þ H]þ), 411.2 (32).
4-Chloro-N-(4-methoxyphenyl)-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-amine (8h). Yield: 47%.
1
M.p. 1858. IR (film): 3278 (NH), 2919, 1578, 1508, 1232, 981, 757. H-NMR (400 MHz, CDCl3): 3.20 (t,
J ¼ 5.0, 2 NCH2CH2NPh); 3.81 (s, MeO); 3.95 – 3.99 (m, 2 NCH2CH2NPh); 6.88 – 6.95 (m, 5 arom. H);
7.25 – 7.30 (m, 2 arom. H); 7.39 – 7.41 (m, 3 arom. H). 13C-NMR (100 MHz, CDCl3): 43.5; 49.2; 55.5; 114.1;
116.7; 120.5; 122.6; 129.2;130.6; 151.0; 156.4; 164.6; 166.0. ESI-MS: 397.3 (100, [M þ H]þ), 399.2 (33).
4-Chloro-N-(3,5-dimethoxyphenyl)-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-amine (8i). Yield:
49%. M.p. 1628. IR (film): 3391 (NH), 2922, 2851, 1588, 1392, 1154, 1063, 989, 909, 731. 1H-NMR
(400 MHz, CDCl3): 3.21 – 3.29 (m, 2 NCH2CH2NPh); 3.78 (s, 2 MeO); 4.04 – 4.12 (m, 2 NCH2CH2NPh);
6.22 – 6.24 (m, 1 arom. H); 6.76 – 6.78 (m, 2 arom. H); 6.97 – 7.10 (m, 4 arom. H); 7.29 – 7.33 (m, 1 arom. H,
NH). ESI-MS: 427.2 (100, [M þ H]þ), 429.2 (32).
General Procedure for the Synthesis of Compounds 9a – 9i and 10a – 10i, Exemplified by the
Preparation of N-[4,6-Di(morpholin-4-yl)-1,3,5-triazin-2-yl]ethane-1,2-diamine (9a). Ethylenediamine
(0.210 g, 3.50 mmol) was added to a suspension of 7a (1.0 g, 3.50 mmol) in THF (10 ml) at r.t., followed
by the addition of K2CO3 (1.45 g, 10.5 mmol). The mixture was stirred at 608 for 3 – 4 h. Then, the
mixture was filtered to remove K2CO3 and excess of solvent was evaporated under vacuum. The residue
thus obtained was dissolved in 30 ml of CHCl3 and washed with brine. The CHCl3 layer was dried
(Na2SO4) and excess of solvent was removed under vacuum to give a crude product, which was purified
by CC (SiO2; AcOEt/hexane) to yield 9a (346 mg, 32%). White solid. M.p. 2218. IR (nujol): 3346 (NH),
1
3232 (NH2), 2924, 2854, 1602, 1550, 1490, 1363, 1290, 1263, 1111, 1021, 857, 802. H-NMR (400 MHz,
(D6)DMSO): 2.37 (br. s, NHCH2CH2NH2); 2.49 (t, J ¼ 6.9, NHCH2CH2NH2); 2.89 – 3.09 (m, 4
NCH2CH2O); 3.44 – 3.49 (m, 4 NCH2CH2O); 6.58 (br. s, NH). 13C-NMR (100 MHz, (D6)DMSO):
41.4; 43.2; 43.7; 66.0; 164.8; 165.8. ESI-MS: 310.2 ([M þ H]þ).
N-[4-(Morpholin-4-yl)-6-(piperidin-1-yl)-1,3,5-triazin-2-yl]ethane-1,2-diamine (9b). Yield: 35%.
M.p. 1598. IR (film): 3408 (NH, NH2), 2856, 1608, 1571, 1518, 1480, 1461, 1435, 1390, 1284, 1247, 1116,
1
1025, 913. H-NMR (400 MHz, (D6)DMSO): 0.85 – 0.87 (m, 2 H); 1.19 – 1.25 (m, 4 H); 1.55 – 1.80 (m,
4 H); 3.33 – 3.45 (m, 4 H); 3.51 – 3.52 (m, 4 H); 3.70 – 3.73 (m, 4 H); 4.07 – 4.10 (m, 2 H); 5.83 (br. s, NH).
13C-NMR (100 MHz, (D6)DMSO): 24.5; 25.6; 43.7; 44.5; 66.6; 163.9; 164.5; 169.5. ESI-MS: 308.2 (15,
[M þ H]þ).
N-(2-Aminoethyl)-N’-cyclohexyl-6-(morpholin-4-yl)-1,3,5-triazine-2,4-diamine (9c). Yield: 27%.
1
Liquid. IR (film): 3309 (NH, NH2), 2927, 2853, 1635, 1582, 1525, 1279, 1114, 757. H-NMR (400 MHz,
(D6)DMSO): 1.07 – 1.29 (m, 4 H); 1.51 – 1.65 (m, 4 H); 1.78 – 1.89 (m, 4 H); 2.80 – 3.67 (m, 15 H). ESI-
MS: 322.2 (18, [M þ H]þ).
N-[4-(Morpholin-4-yl)-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-yl]ethane-1,2-diamine (9d). Yield:
23%. M.p. 1018. IR (film): 3340 (NH, NH2), 2928, 2853, 1708, 1549, 1508, 1445, 1272, 1115, 1025, 811.
1H-NMR (400 MHz, (D6)DMSO): 3.09 – 3.25 (m, 8 H); 3.44 – 3.78 (m, 15 H); 6.76 – 6.78 (m, 1 arom. H);
6.93 – 6.95 (m, 2 arom. H); 7.18 – 7.22 (m, 2 arom. H). ESI-MS: 385.3 (24, [M þ H]þ).
N-(2-Aminoethyl)-N’-(4-methylphenyl)-6-(morpholin-4-yl)-1,3,5-triazine-2,4-diamine (9e). Yield:
21%. M.p. 1668. IR (nujol): 3264 (NH, NH2), 2923, 2854, 1577, 1552, 1512, 1462, 1377, 1351, 1110, 806.

Helvetica Chimica Acta – Vol. 95 (2012)
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1H-NMR (400 MHz, (D6)DMSO): 2.21 (s, MeꢀC6H4); 2.49 – 2.66 (m, NHCH2CH2NH2); 3.22 – 3.24 (br. s,
NH2); 3.54 – 3.65 (m, 2 NCH2CH2O); 6.84 (br. s, NH); 7.02 (d, J ¼ 8.2, 2 arom. H); 7.56 (d, J ¼ 8.2, 2 arom.
H); 8.78 – 8.93 (br. s, NHꢀC6H4Me). ESI-MS: 330.2 (19, [M þ H]þ).
N-(2-Aminoethyl)-N’-(2-methylphenyl)-6-(morpholin-4-yl)-1,3,5-triazine-2,4-diamine (9f). Yield:
24%. M.p. 1708. IR (nujol): 3398 (NH), 3331 (NH2), 2923, 2854, 1681, 1496, 1378, 1149, 1017, 921,
828, 806, 757, 691. 1H-NMR (400 MHz, (D6)DMSO): 2.23 (s, MeꢀC6H4); 2.48 – 2.66 (m,
NHCH2CH2NH2); 3.20 – 3.26 (br. s, NH2); 3.56 – 3.67 (m, 2 NCH2CH2O); 7.06 (d, J ¼ 8.2, 2 arom. H);
7.58 (d, J ¼ 8.2, 2 arom. H); 8.80 – 8.93 (br. s, 1 arom. H, NHꢀC6H4Me). ESI-MS: 330.2 (17, [M þ H]þ).
N-(2-Aminoethyl)-6-(morpholin-4-yl)-N’-[4-(propan-2-yl)phenyl]-1,3,5-triazine-2,4-diamine (9g).
Yield: 26%. M.p. 1738. IR (nujol): 3274 (NH, NH2), 2924, 1596, 1305, 1111, 1068, 1025, 831, 807, 722.
1H-NMR (400 MHz, (D6)DMSO): 1.21 (d, J ¼ 6.8, Me2CH); 2.78 – 2.89 (m, Me2CH, NCH2CH2NH2);
3.31 – 3.39 (m, 2 NCH2CH2O); 3.53 – 3.72 (m, 2 NCH2CH2O); 7.15 (d, J ¼ 8.1, 2 arom. H); 7.67 (d, J ¼ 8.1,
i
2 arom. H); 8.87 – 9.02 (br. s, NH, HNꢀC6H4 Pr). 13C-NMR (100 MHz, (D6)DMSO): 24.0; 38.9; 43.3;
66.0; 119.4; 126.0; 138.2; 141.3; 164.0; 165.1. ESI-MS: 358.2 (18, [M þ H]þ.
N-(2-Aminoethyl)-N’-(4-methoxyphenyl)-6-(morpholin-4-yl)-1,3,5-triazine-2,4-diamine (9h). Yield:
27%. M.p. 1508. IR (nujol): 3263 (NH, NH2), 2923, 2854, 1601, 1581, 1505, 1435, 1278, 1116, 1029, 1012,
895, 828, 805. 1H-NMR (400 MHz, (D6)DMSO): 2.43 – 2.45 (m, NHCH2CH2NH2); 2.63 (t, J ¼ 5.9,
NHCH2CH2NH2); 2.95 – 3.29 (m, 2 NCH2CH2O, NH2); 3.56 – 3.61 (m, 2 NCH2CH2O); 3.65 (s, MeO);
6.77 (d, J ¼ 6.8, 2 arom. H); 7.54 (d, J ¼ 6.8, 2 arom. H); 8.67 – 8.83 (br. s, NH, NHꢀC6H4OMe). 13C-NMR
(100 MHz, (D6)DMSO): 43.3; 55.1; 66.1; 113.6; 121.0; 133.6; 154.6; 164.0; 165.7. ESI-MS: 346.2 (20, [M þ
H]þ).
N-(2-Aminoethyl)-N’-(3,5-dimethoxyphenyl)-6-(morpholin-4-yl)-1,3,5-triazine-2,4-diamine (9i).
Yield: 23%. M.p. 1048. IR (nujol): 3292 (NH, NH2), 2924, 2854, 1595, 1458, 1377, 1152, 1067, 1023,
807, 757. 1H-NMR (400 MHz, (D6)DMSO): 2.48 – 2.49 (m, NHCH2CH2NH2); 3.24 – 3.40 (m, 2
NCH2CH2O, NH2); 3.58 – 3.66 (m, 2 NCH2CH2O); 3.68 (s, 2 MeO); 6.08 (s, 1 arom. H); 6.95 – 7.11 (m,
1 arom. H); 7.71 – 7.89 (m, 1 arom. H); 8.97 – 9.10 (br. s, NH, NHꢀC6H3(OMe)2). ESI-MS: 376.2 (19,
[M þ H]þ).
N-[4-(4-Phenylpiperazin-1-yl)-6-(piperidin-1-yl)-1,3,5-triazin-2-yl]ethane-1,2-diamine (10a). Yield:
29%. M.p. 1228. IR (film): 3297 (NH, NH2), 2933, 2852, 1526, 1445, 1371, 1271, 1231, 998, 808, 756.
1H-NMR (400 MHz, (D6)DMSO): 1.44 – 1.57 (m, 6 H); 2.48 – 2.68 (m, NHCH2CH2NH2); 3.10 – 3.26 (m,
CH2NCH2); 3.41 – 3.52 (m, 2 NCH2CH2NPh); 3.64 – 3.77 (m, 2 NCH2CH2NPh); 6.54 – 6.69 (br. s, NH);
6.78 – 6.86 (m, 1 arom. H); 6.94 – 6.96 (m, 2 arom. H); 7.19 – 7.23 (m, 2 arom. H). ESI-MS: 383.3 (25,
[M þ H]þ).
N-(2-Aminoethyl)-N’-cyclohexyl-6-(4-phenylpiperazin-1-yl)-1,3,5-triazine-2,4-diamine (10b). Yield:
27%. M.p. 988. IR (nujol): 3297, 2922, 2853, 1538, 1455, 1374, 1231, 1140, 1015, 982, 930, 810, 760, 693.
1H-NMR (400 MHz, (D6)DMSO): 1.09 – 1.19 (m, 6 H); 1.53 – 1.79 (m, 6 H); 2.48 – 2.49 (m,
NCH2CH2NH2); 2.71 – 2.82 (m, NHCH2CH2NH2); 3.09 – 3.30 (m, 2 NCH2CH2NPh); 3.73 – 3.76 (m, 2
NCH2CH2NPh); 6.76 – 6.80 (m, NH, NHꢀcyclohexyl); 6.94 – 6.96 (m, 2 arom. H); 7.18 – 7.22 (m, 2 arom.
H). 13C-NMR (100 MHz, (D6)DMSO): 24.9; 32.7; 42.4; 48.4; 115.9; 119.2; 129.0; 151.1; 164.6; 166.0. ESI-
MS: 397.3 (23, [M þ H]þ).
N-[4,6-Bis(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-yl]ethane-1,2-diamine (10c). Yield: 24%. M.p.
1138. IR (nujol): 3263 (NH, NH2), 2921, 2726, 1651, 1622, 1538, 1455, 1377, 1289, 1228, 1015, 927, 742.
1H-NMR (400 MHz, (D6)DMSO): 2.62 – 2.65 (m, NHCH2CH2NH2); 3.10 – 3.25 (m, 4 NCH2CH2NPh);
3.71 – 3.84 (m, 4 NCH2CH2NPh); 6.74 – 6.78 (m, 2 arom. H, NH); 6.92 – 6.94 (m, 4 arom. H); 7.17 – 7.21
(m, 4 arom. H). ESI-MS: 460.3 (27, [M þ H]þ).
N-(2-Aminoethyl)-N’-(4-methylphenyl)-6-(4-phenylpiperazin-1-yl)-1,3,5-triazine-2,4-diamine (10d).
Yield: 21%. M.p. 1158. IR (nujol): 3292 (NH, NH2), 2920, 2726, 1463, 1377, 1325, 1267, 1232, 1152, 1002,
912, 756. 1H-NMR (400 MHz, (D6)DMSO): 1.92 (br. s, NH2); 2.30 (s, MeꢀC6H4); 3.20 – 3.54 (m, 2
NCH2CH2NPh, NHCH2CH2NH2); 3.94 – 4.09 (m, 2 NCH2CH2NPh); 6.85 – 6.96 (m, 3 arom. H); 7.10 –
7.12 (m, 2 arom. H); 7.21 – 7.30 (m, 2 arom. H); 7.36 – 7.43 (m, 2 arom. H); 8.11 (br. s, NHꢀC6H4Me,
NH). ESI-MS.: 405.3 (18, [M þ H]þ).
N-(2-Aminoethyl)-N’-(2-methylphenyl)-6-(4-phenylpiperazin-1-yl)-1,3,5-triazine-2,4-diamine (10e).
Yield: 19%. M.p. 1318. IR (film): 3417 (NH, NH2), 2938, 1704, 1504, 1434, 1245, 1174, 1158, 1028, 753.

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Helvetica Chimica Acta – Vol. 95 (2012)
1H-NMR (400 MHz, (D6)DMSO): 1.92 (br. s, NH2); 2.30 (s, MeꢀC6H4); 3.20 – 3.54 (m, NHCH2CH2NH2,
2 NCH2CH2NPh); 3.94 – 4.09 (m, 2 NCH2CH2NPh); 6.85 – 6.96 (m, 3 arom. H); 7.10 – 7.12 (m, 2 arom.
H); 7.21 – 7.30 (m, 2 arom. H); 7.36 – 7.43 (m, 2 arom. H); 8.11 (br. s, HNꢀC6H4Me, NH). ESI-MS: 405.3
(24, [M þ H]þ).
N-(2-Aminoethyl)-N’-(4-ethylphenyl)-6-(4-phenylpiperazin-1-yl)-1,3,5-triazine-2,4-diamine (10f).
Yield: 30%. M.p. 1398. IR (nujol): 3297 (NH, NH2), 2924, 2854, 1547, 1505, 1436, 1227, 1155, 1010,
1
921, 761. H-NMR (400 MHz, (D6)DMSO): 1.12 (t, J ¼ 7.5, MeCH2); 2.46 – 2.52 (m, NHCH2CH2NH2);
2.61 – 2.66 (m, MeCH2, NHCH2CH2NH2); 3.21 – 3.25 (m, 2 NCH2CH2NPh); 3.75 – 3.90 (m, 2
NCH2CH2NPh); 6.74 – 6.84 (m, 2 arom. H); 6.94 (d, J ¼ 7.3, 2 arom. H); 6.96 – 7.03 (m, 1 arom. H);
7.17 – 7.21 (m, 2 arom. H); 7.59 (d, J ¼ 7.3, 2 arom. H); 8.77 – 8.92 (br. s, NHꢀC6H4Et, NH).13C-NMR
(100 MHz, (D6)DMSO): 15.8; 27.5; 39.9; 48.4; 115.9; 119.5; 127.5; 128.9; 136.5; 138.2; 151.1; 164.1; 166.0.
ESI-MS: 419.8 (27, [M þ H]þ).
N-(2-Aminoethyl)-6-(4-phenylpiperazin-1-yl)-N’-[4-(propan-2-yl)phenyl]-1,3,5-triazine-2,4-diamine
(10g). Yield: 28%. M.p. 1658. IR (nujol): 3313, 2922, 2726, 2370, 1686, 1585, 1537, 1463, 1455, 1377, 1258,
1114, 1008, 722. 1H-NMR (400 MHz, (D6)DMSO): 1.23 (d, J ¼ 6.8, Me2CH); 2.86 – 2.89 (m,
NHCH2CH2NH2, Me2CH); 3.13 – 3.39 (m, 2 NCH2CH2NPh); 3.54 – 4.11 (m, 2 NCH2CH2NPh); 6.88 –
6.91 (m, 1 arom. H); 6.96 (d, J ¼ 8.2, 2 arom. H); 7.16 (d, J ¼ 8.2, 2 arom. H); 7.26 – 7.31 (m, 2 arom.
i
H); 7.45 – 7.47 (m, 2 arom. H); 8.87 (br. s, HNꢀC6H4 Pr, NH). ESI-MS: 433.2 (30, [M þ H]þ).
N-(2-Aminoethyl)-N’-(4-methoxyphenyl)-6-(4-phenylpiperazin-1-yl)-1,3,5-triazine-2,4-diamine
(10h). Yield: 23%. M.p. 1628. IR (film): 3403 (NH, NH2), 2919, 1575, 1520, 1479, 1232, 1165, 995, 980,
751. 1H-NMR (400 MHz, (D6)DMSO): 2.48 – 2.49 (m, NHCH2CH2NH2); 2.70 – 2.73 (t, J ¼ 5.1,
NCH2CH2NH2); 3.13 – 3.41 (m, 2 NCH2CH2NPh); 3.70 (s, MeO); 3.79 – 3.92 (m, 2 NCH2CH2NPh);
6.77 – 6.82 (m, 3 arom. H); 6.96 (d, J ¼ 7.8, 2 arom. H); 7.19 – 7.23 (m, 2 arom. H); 7.60 (d, J ¼ 7.8, 2 arom.
H); 8.71 – 8.97 (br. s, NHꢀC6H4OMe, NH). ESI-MS: 421.2 (25, [M þ H]þ).
N-(2-Aminoethyl)-N’-(3,5-dimethoxyphenyl)-6-(4-phenylpiperazin-1-yl)-1,3,5-triazine-2,4-diamine
1
(10i). Yield: 21%. M.p. 908. IR (film): 3271, 2964, 2929, 1575, 1514, 1421, 1231, 982, 831, 758. H-NMR
(400 MHz, (D6)DMSO): 2.45 – 2.67 (m, NHCH2CH2NH2); 3.11 – 3.21 (m, 2 NCH2CH2NPh); 3.66 (s, 2
MeO); 3.74 – 3.82 (m, 2 NCH2CH2NPh); 6.03 (s, 1 arom. H); 6.74 – 6.77 (m, 1 arom. H); 6.93 – 7.05 (m, 4
arom. H); 7.16 – 7.20 (m, 2 arom. H); 8.83 – 8.99 (br. s, NHꢀC6H3(OMe)2, NH). ESI-MS: 451.3 (28, [M þ
H]þ).
General Procedure for the Synthesis of Compounds 12a – 12i and 13a – 13i, Exemplified by the
Preparation of N-(2-{[4,6-Di(morpholin-4-yl)-1,3,5-triazin-2-yl]amino}ethyl)-4-[6-(4-methylphenyl)-
1,2,4,5-tetroxan-3-yl]benzamide (12a). Compound 11 (100 mg, 0.33 mmol) was dissolved in 10 ml of
THF, and Et3N (40 mg, 0.66 mmol) was added. After 15 min, ClCOOEt (36 mg, 0.33 mmol) was added,
the mixture was stirred for 30 min, and 9a (204 mg, 0.66 mmol) was added. The mixture was stirred for
2 h, and the progress of the reaction was monitored by TLC. After completion of the reaction, the
product was extracted with CHCl3. The layer was dried (Na2SO4), and the solvent was removed under
vacuum, and the crude product was purified by CC (SiO2; AcOEt/hexane). Yield of 12a: 36 mg (19%).
M.p. 1588. IR (film): 3346 (NH), 2854, 1713 (C¼O), 1502, 1257, 1112, 1006, 858, 807, 752. 1H-NMR
(400 MHz, CDCl3): 2.39 (s, Me); 3.50 – 3.71 (m, NHCH2CH2NHCO, 4 NCH2CH2O); 5.37 (br. s, NH);
6.88 (s, OCHO); 6.94 (s, OCHO), 7.23 (d, J ¼ 8.2, 2 arom. H); 7.38 (d, J ¼ 8.2, 2 arom. H); 7.51 (d, J ¼ 8.2,
2 arom. H);7.67 (br. s, CONH); 7.72 (d, J ¼ 8.2, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 21.5; 39.5; 42.9;
43.7; 66.8; 107.2; 108.4; 127.4; 127.8; 129.5; 133.6; 137.2; 141.8; 164.9; 166.8. ESI-MS: 594.2 (38, [M þ
H]þ). Anal. calc. for C29H35N7O7 (593.63): C 58.67, H 5.94, N 16.52; found: C 58.89, H 5.69, N 16.85.
4-[6-(4-Methylphenyl)-1,2,4,5-tetroxan-3-yl]-N-(2-{[4-(morpholin-4-yl)-6-(piperidin-1-yl)-1,3,5-tri-
azin-2-yl]amino}ethyl)benzamide (12b). Yield: 17%. M.p. 1598. IR (film): 3408 (NH), 2856, 1608, 1571,
1518, 1461, 1390, 1247, 1116, 980, 745. 1H-NMR (300 MHz, (D6)DMSO): 1.18 – 1.25 (m, 6 H); 1.56 – 1.65
(m, 4 H); 2.40 (s, Me); 3.34 – 3.52 (m, 4 H); 3.72 – 3.80 (m, 4 H); 4.04 – 4.11 (m, 4 H); 6.94 – 6.98 (m, 2
OCHO); 7.20 (d, J ¼ 7.8, 2 arom. H); 7.67 – 7.70 (d, J ¼ 7.8, 2 arom. H); 7.76 – 8.07 (m, 4 arom. H); 8.65 (br.
s, CONH); 9.96 (br. s, NH). ESI-MS: 592.2 (36, [M þ H]þ). Anal. calc. for C30H37N7O6 (591.66): C 60.90,
H 6.30, N 16.57; found: C 61.22, H 6.12, N 16.79.
N-(2-{[4-(Cyclohexylamino)-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]amino}ethyl)-4-[6-(4-methylphen-
yl)-1,2,4,5-tetroxan-3-yl]benzamide (12c). Yield: 17%. M.p. 1768. IR (film): 3340 (NH), 2897, 2855, 1713

Helvetica Chimica Acta – Vol. 95 (2012)
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(C¼O), 1527, 1360, 1262, 1161, 1115, 1006, 910, 809, 759, 732. 1H-NMR (300 MHz, (D6)DMSO): 1.11 –
1.20 (m, 6 H); 1.53 – 1.78 (m, 5 H); 2.36 (s, Me); 3.11 – 3.58 (m, 8 H); 3.92 – 3.99 (m, 5 H); 7.06 (s,
OCHO); 7.13 (s, OCHO); 7.28 – 7.32 (m, 2 arom. H); 7.39 – 7.49 (m, 2 arom. H); 7.79 – 8.00 (m, 4 arom.
H); 8.63 – 8.69 (br. s, CONH); 9.94 – 10.07 (br. s, NH). 13C-NMR (100 MHz, (D6)DMSO): 18.8; 21.1;
21.4; 24.9; 25.4; 31.9; 32.6; 43.1; 66.1; 107.3; 107.4; 127.4; 128.0; 129.1; 129.3; 129.6; 129.7; 143.0; 164.8;
167.0; 167.4; 192.6; 192.9. ESI-MS: 606.3 (34, [M þ H]þ). Anal. calc. for C31H39N7O6 (605.68): C 61.47, H
6.49, N 16.19; found: C 61.76, H 6.21, N 16.51.
4-[6-(4-Methylphenyl)-1,2,4,5-tetroxan-3-yl]-N-(2-{[4-(morpholin-4-yl)-6-(4-phenylpiperazin-1-yl)-
1,3,5-triazin-2-yl]amino}ethyl)benzamide (12d). Yield: 18%. M.p. 1588. IR (film): 3338 (NH), 2854, 1708
1
(C¼O), 1528, 1438, 1363, 1262, 1232, 1160, 1115, 1006, 759. H-NMR (300 MHz, (D6)DMSO): 2.35 (s,
Me); 3.06 – 3.93 (m, 20 H); 6.73 – 6.82 (m, 2 arom. H); 6.91 – 7.08 (m, 1 arom H, OCHO); 7.15 – 7.23 (m, 1
arom. H, 2 OCHO); 7.42 – 7.48 (m, 2 arom. H); 7.75 – 7.83 (m, 2 arom. H); 7.89 – 8.10 (m, 4 arom. H);
8.58 – 8.69 (br. s, CONH); 9.90 – 10.00 (br. s, NH). ESI-MS: 669.3 (39, [M þ H]þ). Anal. calc. for
C35H40N8O6 (668.74): C 62.86, H 6.03, N 16.76; found: C 62.58, H 6.31, N 16.98.
N-[2-({4-[(4-Methylphenyl)amino]-6-(morpholin-4-yl)-1,3,5-triazin-2-yl}amino)ethyl]-4-[6-(4-meth-
ylphenyl)-1,2,4,5-tetroxan-3-yl]benzamide (12e). Yield: 16%. M.p. 1758. IR (film): 3327 (NH), 2963,
2924, 2248, 1704 (C¼O), 1515, 1360, 1261, 1112, 1023, 910, 734. 1H-NMR (300 MHz, (D6)DMSO): 2.35 (s,
Me); 2.42 (s, MeꢀC6H4); 3.33 – 3.64 (m, 2 NCH2CH2O, NHCH2CH2NHCO); 7.05 (s, OCHO); 7.13 (s,
OCHO); 7.30 (d, J ¼ 7.8, 2 arom. H); 7.46 (d, J ¼ 7.8, 2 arom. H); 7.56 (d, J ¼ 8.1, 2 arom. H); 7.64 (d, J ¼
8.1, 2 arom. H); 7.97 – 8.03 (m, 4 arom. H); 8.63 (br. s, CONH); 8.81 – 8.96 (br. s, NHꢀC6H4Me, NH).
13C-NMR (100 MHz, (D6)DMSO): 20.4; 21.2; 39.9; 65.9; 106.8; 107.6; 119.7; 127.8; 127.9; 128.0; 129.5;
133.3; 137.9; 141.6; 164.2; 165.8. ESI-MS: 614.2 (32, [M þ H]þ). Anal. calc. for C32H35N7O6 (613.66): C
62.63, H 5.75, N 15.98; found: C 62.35, H 5.47, N 16.30.
N-[2-({4-[(2-Methylphenyl)amino]-6-(morpholin-4-yl)-1,3,5-triazin-2-yl}amino)ethyl]-4-[6-(4-meth-
ylphenyl)-1,2,4,5-tetroxan-3-yl]benzamide (12f). Yield: 17%. M.p. 1818. IR (film): 3276 (NH), 2925,
2852, 1697 (C¼O), 1508, 1460, 1231, 1158, 1010, 754. 1H-NMR (300 MHz, (D6)DMSO): 2.36 (s,
MeꢀC6H4); 2.43 (s, Me); 3.34 – 3.65 (m, 2 NCH2CH2O, NHCH2CH2NHCO); 7.07 (s, OCHO); 7.11 (s,
OCHO); 7.31 (d, J ¼ 7.8, 2 arom. H); 7.47 (d, J ¼ 7.8, 2 arom. H); 7.57 (d, J ¼ 8.1, 2 arom. H); 7.64 (d, J ¼
8.1, 2 arom. H); 7.97 – 8.01 (m, 4 arom. H); 8.65 (br. s, CONH); 8.83 – 8.97 (br. s, NHꢀC6H4Me, NH). ESI-
MS: 614.2 (35, [M þ H]þ). Anal. calc. for C32H35N7O6 (613.66): C 62.63, H 5.75, N 15.98; found: C 62.41,
H 5.99, N 15.69.
4-[6-(4-Methylphenyl)-1,2,4,5-tetroxan-3-yl]-N-(2-{[4-(morpholin-4-yl)-6-{[4-(propan-2-yl)phen-
yl]amino}-1,3,5-triazin-2-yl]amino}ethyl)benzamide (12g). Yield: 18%. M.p. 1548. IR (film): 3326 (NH),
2960, 1704 (C¼O), 1505, 1418, 1275, 1115, 1023, 755. 1H-NMR (300 MHz, (D6)DMSO): 1.10 (d, J ¼ 6.6,
Me2CH); 2.35 (s, Me); 2.70 – 2.79 (m, Me2CH); 3.15 – 3.62 (m, 2 NCH2CH2O, NHCH2CH2NHCO);
6.94 – 7.25 (m, 2 OCHO); 7.25 (d, J ¼ 7.2, 2 arom. H); 7.34 (d, J ¼ 7.5, 2 arom. H); 7.42 (d, J ¼ 7.2, 2 arom.
H); 7.55 – 7.61 (m, 2 arom. H); 7.74 – 7.80 (m, 2 arom. H); 7.85 – 8.08 (m, 2 arom. H); 8.62 – 8.70 (br. s,
CONH); 8.81 – 8.96 (br. s, NH); 9.90 – 10.02 (br. s, NHꢀC6H4Me). 13C-NMR (100 MHz, (D6)DMSO):
20.8; 24.1; 38.9; 40.1; 66.3; 106.8; 107.8; 119.5; 126.0; 127.9; 128.0; 129.5; 132.9; 134.1; 138.1; 141.1; 145.6;
163.8; 166.0. ESI-MS: 642.3 (38, [M þ H]þ). Anal. calc. for C34H39N7O6 (641.72): C 63.64, H 6.13, N 15.28;
found: C 63.36, H 6.35, N 15.39.
N-[2-({4-[(4-Methoxyphenyl)amino]-6-(morpholin-4-yl)-1,3,5-triazin-2-yl}amino)ethyl]-4-[6-(4-
methylphenyl)-1,2,4,5-tetroxan-3-yl]benzamide (12h). Yield: 15%. M.p. 1438. IR (film): 3338 (NH),
2926, 2857, 1702 (C¼O), 1540, 1508, 1244, 1026, 809, 732. 1H-NMR (300 MHz, (D6)DMSO): 2.36 (s, Me);
3.29 – 3.65 (m, 2 NCH2CH2O, NHCH2CH2NHCO); 3.69 (s, MeO); 6.80 – 6.83 (m, 2 OCHO); 7.27 (d, J ¼
7.8, 2 arom. H); 7.39 (d, J ¼ 7.8, 2 arom. H); 7.59 (d, J ¼ 7.8, 2 arom. H); 7.78 – 7.84 (m, 4 arom. H); 7.88 –
8.03 (m, 2 arom. H); 8.60 – 8.84 (br. s, CONH, NH); 9.95 – 10.00 (br. s, NHꢀC6H4OMe). ESI-MS: 630.2
(37, [M þ H]þ).
N-[2-({4-[(3,5-Dimethoxyphenyl)amino]-6-(morpholin-4-yl)-1,3,5-triazin-2-yl}amino)ethyl]-4-[6-
(4-methylphenyl)-1,2,4,5-tetroxan-3-yl]benzamide (12i). Yield: 16%. M.p. 1548. IR (film): 3338 (NH),
2924, 1702 (C¼O), 1591, 1508, 1447, 1358, 1266, 1172, 1153, 809. 1H-NMR (300 MHz, (D6)DMSO): 2.31
(s, Me); 3.10 – 3.95 (m, 2 NCH2CH2O, NHCH2CH2NHCO, 2 MeO); 6.02 (s, 1 arom. H); 7.01 (s, OCHO);
7.09 (s, OCHO); 7.26 (d, J ¼ 7.8, 2 arom. H); 7.42 (d, J ¼ 7.8, 2 arom. H); 7.60 (d, J ¼ 7.8, 2 arom. H); 7.75 –

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Helvetica Chimica Acta – Vol. 95 (2012)
7.94 (m, 4 arom. H); 8.62 (br. s, CONH); 8.84 – 9.01 (br. s, NH); 9.90 – 10.03 (br. s, NHꢀC6H3(OMe)2).
13C-NMR (100 MHz, (D6)DMSO): 21.3; 43.3; 66.1; 97.5; 106.8; 107.6; 128.0; 129.6; 137.3; 142.2; 160.2;
166.0. ESI-MS: 660.2 (35, [M þ H]þ).
4-[6-(4-Methylphenyl)-1,2,4,5-tetroxan-3-yl]-N-(2-{[4-(4-phenylpiperazin-1-yl)-6-(piperidin-1-yl)-
1,3,5-triazin-2-yl]amino}ethyl)benzamide (13a). Yield: 18%. M.p. 1298. IR (film): 3340 (NH), 2930,
1
2852, 1702 (C¼O), 1530, 1499, 1270, 1231, 1153, 808. H-NMR (300 MHz, (D6)DMSO): 1.44 – 1.57 (m,
6 H); 2.36 (s, Me); 3.10 – 3.90 (m, 16 H); 6.77 – 6.81 (m, 2 H); 6.94 – 7.13 (m, 2 OCHO); 7.19 – 7.24 (m, 2
arom. H); 7.28 – 7.32 (m, 2 arom. H); 7.40 – 7.48 (m, 2 arom. H); 7.79 – 7.84 (m, 2 arom. H); 7.89 – 8.10 (m, 3
arom. H); 8.64 – 8.71 (br. s, CONH); 9.95 – 10.06 (br. s, NH). ESI-MS: 667.3 (37, [M þ H]þ). Anal. calc.
for C36H42N8O5 (666.77): C 64.85, H 6.35, N 16.81; found: C 64.55, H 6.65, N 16.51.
N-(2-{[4-(Cyclohexylamino)-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-yl]amino}ethyl)-4-[6-(4-meth-
ylphenyl)-1,2,4,5-tetroxan-3-yl]benzamide (13b). Yield: 16%. M.p. 1458. IR (film): 3388 (NH), 2929,
1708 (C¼O), 1523, 1364, 1222, 1011, 758. 1H-NMR (300 MHz, (D6)DMSO): 1.24 – 1.91 (m, 10 H); 2.37 (s,
3 H); 3.10 – 3.78 (m, 13 H); 6.79 – 7.83 (m, 4 H); 6.97 – 7.05 (m, 2 OCHO); 7.22 – 7.43 (m, 4 arom. H);
7.80 – 8.12 (m, 6 arom. H); 8.62 – 8.68 (br. s, CONH); 9.96 – 10.07 (br. s, NH). 13C-NMR (100 MHz,
(D6)DMSO): 18.8; 21.1; 21.1; 21.4; 24.9; 32.6; 43.1; 66.1; 105.8;107.3; 107.4; 126.2; 127.9; 128.0; 129.1;
129.3; 129.4; 129.7; 131.0; 137.4; 141.5; 143.0; 145.3; 167.4; 192.7. ESI-MS: 681.3 (40, [M þ H]þ).
N-(2-{[4,6-Bis(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-yl]amino}ethyl)-4-[6-(4-methylphenyl)-
1,2,4,5-tetroxan-3-yl]benzamide (13c). Yield: 16%. M.p. 1528. IR (film): 3338 (NH), 2924, 1702 (C¼O),
1508, 1439, 1267, 1231, 1004, 759. 1H-NMR (300 MHz, (D6)DMSO): 2.36 (s, 3 H); 3.33 – 3.84 (m, 4
NHCH2CH2NPh, NHCH2CH2N); 6.89 – 6.95 (m, 4 arom. H); 7.05 (s, OCHO); 7.13 (s, OCHO); 7.25 – 7.48
(m, 4 arom. H); 7.67 – 7.70 (m, 2 arom. H); 7.79 – 7.98 (m, 6 arom. H); 8.23 – 8.25 (m, 2 arom. H); 8.65 –
8.71 (br. s, CONH); 9.94 – 10.07 (br. s, NH). 13C-NMR (100 MHz, (D6)DMSO): 25.4; 43.2; 59.5; 66.1;
105.8; 107.3; 107.4; 126.2; 127.7; 127.9; 128.0; 129.1; 129.4; 129.7; 131.0; 131.2; 137.4; 141.5; 156.3; 164.9;
165.8; 192.6. ESI-MS: 744.3 (45, [M þ H]þ). Anal. calc. for C41H45N9O5 (643.85): C 66.20, H 6.10, N 16.95;
found: C 66.42, H 6.31, N 16.75.
N-[2-({4-[(4-Methylphenyl)amino]-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-yl}amino)ethyl]-4-[6-
(4-methylphenyl)-1,2,4,5-tetroxan-3-yl]benzamide (13d).Yield: 17%. M.p. 1378. IR (film): 3227 (NH),
2925, 1702 (C¼O), 1577, 1544, 1365, 1281, 1232, 1159, 1012, 808, 758. 1H-NMR (300 MHz, (D6)DMSO):
2.23 (s, MeꢀC6H4); 2.36 (s, Me); 3.14 – 3.96 (m, 2 NCH2CH2NPh, NHCH2CH2NHCO); 6.79 – 6.82 (m, 1
arom. H); 6.97 – 7.15 (m, 2 arom. H, 2 OCHO); 7.19 – 7.32 (m, 4 arom. H); 7.39 – 7.42 (m, 2 arom. H);
7.58 – 7.66 (m, 4 arom. H); 7.78 – 7.84 (m, 2 arom. H); 7.90 – 8.02 (m, 2 arom. H); 8.63 – 8.61 (br. s, CONH);
9.25 (br. s, NH); 9.95 – 10.06 (br. s, NHꢀC6H4 Me). ESI-MS: 689.3 (39, [M þ H]þ).
N-[2-({4-[(2-Methylphenyl)amino]-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-yl}amino)ethyl]-4-[6-
(4-methylphenyl)-1,2,4,5-tetroxan-3-yl]benzamide (13e). Yield: 15%. M.p. 1488. IR (film): 3390 (NH),
2915, 1600, 1578, 1528, 1494, 1231, 1130, 980, 799, 756. 1H-NMR (300 MHz, (D6)DMSO): 2.36 (s, 2 Me);
3.14 – 3.96 (m, 2 NCH2CH2NPh, NHCH2CH2NHCO); 6.79 – 6.82 (m, 1 arom. H); 6.97 – 7.11(m, 2 arom.
H, 2 OCHO); 7.19 – 7.32 (m, 2 arom. H); 7.39 – 7.42 (m, 4 arom. H); 7.58 – 7.66 (m, 4 arom. H); 7.78 – 7.84
(m, 2 arom. H); 7.90 – 8.02 (m, 2 arom. H); 8.65 (br. s, CONH); 9.25 (br. s, NH); 9.95 – 10.05 (br. s,
NHꢀC6H4 Me). ESI-MS: 689.3 (23, [M þ H]þ). Anal. calc. for C38H40N8O5 (688.77): C 66.26, H 5.85, N
16.27; found: C 66.46, H 5.65, N 16.57.
N-[2-({4-[(4-Ethylphenyl)amino]-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-yl}amino)ethyl]-4-[6-
(4-methylphenyl)-1,2,4,5-tetroxan-3-yl]benzamide (13f). Yield: 16%. M.p. 1358. IR (film): 3315 (NH),
2963, 1702 (C¼O), 1508, 1420, 1364, 1232, 1159, 1011, 758. 1H-NMR (300 MHz, (D6)DMSO): 1.12 (t, J ¼
7.5, MeCH2); 2.36 (s, Me); 2.44 – 2.53 (m, MeCH2); 3.14 – 3.84 (m,
2 NCH2CH2NPh,
NHCH2CH2NHCO); 6.77 – 6.82 (m, 1 arom. H); 6.96 – 6.98 (m, 2 arom. H); 7.05 – 7.12 (m, 2 OCHO);
7.19 – 7.32 (m, 4 arom. H); 7.39 – 7.48 (m, 2 arom. H); 7.64 – 7.72 (m, 2 arom. H); 7.78 – 7.84 (m, 2 arom. H);
7.91 – 8.04 (m, 4 arom. H); 8.68 – 8.75 (br. s, CONH); 8.86 – 9.01 (br. s, NH); 9.99 – 10.05 (br. s,
NHꢀC6H4Et). ESI-MS: 703.3 (41, [M þ H]þ).
4-[6-(4-Methylphenyl)-1,2,4,5-tetroxan-3-yl]-N-(2-{[4-(4-phenylpiperazin-1-yl)-6-{[4-(propan-2-yl)-
phenyl]amino}-1,3,5-triazin-2-yl]amino}ethyl)benzamide (13g). Yield: 18%. M.p. 1338. IR (film): 3314
(NH), 2959, 1702 (C¼O), 1508, 1419, 1365, 1232, 1159, 1012, 927, 732. 1H-NMR (300 MHz, (D6)DMSO):
1.16 (d, J ¼ 6.9, Me2CH); 2.35 (s, Me); 2.76 – 2.85 (sept., Me2CH); 3.14 – 3.84 (m, 2 NCH2CH2NPh,

Helvetica Chimica Acta – Vol. 95 (2012)
1193
NHCH2CH2NHCO); 6.77 – 6.82 (m, 1 arom. H); 6.96 (d, J ¼ 7.8, 2 arom. H); 7.04 (s, OCHO); 7.11 (s,
OCHO); 7.20 – 7.32 (m, 4 arom. H); 7.39 – 7.48 (m, 4 arom. H); 7.64 (d, J ¼ 7.8, 2 arom. H); 7.78 – 7.84 (m, 2
arom. H); 7.91 – 8.00 (m, 2 arom. H); 8.33 – 8.69 (br. s, CONH); 8.96 (br. s, NH); 9.95 – 10.05 (br. s,
i
NHꢀC6H4 Pr). ESI-MS: 717.3 (46, [M þ H]þ). Anal. calc. for C40H44N8O5 (716.83): C 67.02, H 6.19, N
15.63; found: C 67.22, H 6.39, N 15.42.
N-[2-({4-[(4-Methoxyphenyl)amino]-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-yl}amino)ethyl]-4-
[6-(4-methylphenyl)-1,2,4,5-tetroxan-3-yl]benzamide (13h). Yield: 16%. M.p. 1718 IR (film): 3327 (NH),
2925, 2853, 1699 (C¼O), 1505, 1445, 1232, 1159, 1035, 928, 760. 1H-NMR (300 MHz, (D6)DMSO): 2.36
(s, Me); 3.13 – 3.47 (m, 2 NCH2CH2NPh, NHCH2CH2NHCO); 3.70 (s, MeO); 3.82 (m, 2 NCH2CH2NPh);
6.77 – 6.82 (m, 1 arom. H); 6.96 – 7.12 (m, 2 arom. H, 2 OCHO); 7.19 – 7.24 (m, 4 arom. H); 7.28 – 7.33 (m,
2 arom. H); 7.40 – 7.52 (m, 2 arom. H); 7.61 – 7.67 (m, 2 arom. H); 7.79ꢀ7.84 (m, 2 arom. H); 7.93 – 8.02 (m,
2 arom. H); 8.67 – 8.78 (br. s, CONH); 8.94 (br. s, NH); 9.94 – 10.05 (br. s, NHꢀC6H4OMe). ESI-MS:
705.3 (38, [M þ H]þ).
N-[2-({4-[(3,5-Dimethoxyphenyl)amino]-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-yl}amino)eth-
yl]-4-[6-(4-methylphenyl)-1,2,4,5-tetroxan-3-yl]benzamide (13i). Yield: 18%. M.p. 1388. IR (film): 3346
(NH), 2932, 1707 (C¼O), 1593, 1508, 1448, 1232, 1152, 913, 808, 742. 1H-NMR (300 MHz, (D6)DMSO):
2.35 (s, Me); 3.14 – 3.85 (m, 2 NCH2CH2NPh, NHCH2CH2NHCO, 2 MeO); 6.07 (s, 1 arom. H); 6.77 – 6.82
(m, 2 arom. H); 6.97 – 7.12 (m, 2 arom. H, 2 OCHO); 7.20 – 7.25 (m, 2 arom. H); 7.30 (d, J ¼ 8.1, 2 arom.
H); 7.46 (d, J ¼ 7.8, 2 arom. H); 7.64 (d, J ¼ 8.1, 2 arom. H); 7.91 – 8.02 (m, 3 arom. H); 8.65 (br. s, CONH);
8.90 – 9.06 (br. s, NH); 10.05 (br. s, NHꢀC6H3(OMe)2). ESI-MS: 735.3 (43, [M þ H]þ).
General Procedure for the Synthesis of Compounds 16a – 16m and 17a – 17h, Exemplified by the
Preparation of 3-(4-Methoxyphenyl)-9-[(4-methylphenyl)sulfonyl]-1,2,4,5-tetraoxa-9-azaspiro[5.5]unde-
cane (16j). A mixture of 15a (800 mg, 3.15 mmol), 30% H2O2 (0.71 ml, 6.31 mmol), and methyltrioxo-
rhenium (MTO; 0.79 mg, 0.003 mmol) in 50 ml of 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) was stirred
for 2 h at r.t. and 4-MeOꢀC6H4CHO (860 mg, 6.31 mmol) was added to the mixture, followed by the
addition of 54% Et2O soln. of HBF4 (511 mg, 3.15 mmol). The mixture was stirred for an additional h at
r.t. After completion of the reaction (TLC), CHCl3 was added to the mixture, and the layer was washed
with sat. NaHSO3 soln. followed by sat. soln. of NaHCO3. The CHCl3 layer was then dried (Na2SO4), and
solvent was evaporated under reduced pressure. The crude product was then purified by CC (SiO2,
CHCl3/hexane) to give 16j. Yield: 266 mg (20%). M.p. 1768. IR (film): 2925, 2854, 1611, 1517, 1465, 1345,
1
1333, 1255, 1164, 1078, 1039, 993, 963. H-NMR (400 MHz, CDCl3): 1.87 (t, J ¼ 5.7, NCH2CH2); 2.44 (s,
Me); 2.65 (t, J ¼ 5.7, NCH2CH2); 3.13 (t, J ¼ 5.7, NCH2CH2); 3.21 (t, J ¼ 5.7, NCH2CH2); 3.81 (s, MeO);
6.56 (s, OCHO); 6.89 (d, J ¼ 8.1, 2 arom. H); 7.32 – 7.34 (m, 4 arom. H); 7.64 (d, J ¼ 8.1, 2 arom.
H).13C-NMR (100 MHz, CDCl3): 21.5; 29.7; 31.1; 42.0; 43.1; 55.3; 105.7; 108.0; 114.1; 123.1; 127.6; 129.2;
129.8; 132.9; 143.9; 161.8. HR-ESI-MS: 421.3566 (Mþ, C20H23NO7Sþ; calc. 421.1195).
12-Methyl-3-[(4-methylphenyl)sulfonyl]-7,8,15,16-tetraoxa-3-azadispiro[5.2.5.2]hexadecane (16a).
Yield: 36%. M.p. 1978. IR (film): 2956, 2925, 1331, 1232, 1156, 1039, 993, 811, 729. 1H-NMR
(300 MHz, CDCl3): 0.88 – 1.80 (m, 14 H); 2.43 (s, 3 H); 2.56 – 2.60 (m, 2 H); 3.03 – 3.16 (m, 4 H); 7.30 (d,
J ¼ 8.1, 2 arom. H); 7.61 (d, J ¼ 8.1, 2 arom. H). ESI-MS: 398.2 (18, [M þ H]þ). Anal. calc. for C19H27O6S
(397.49): C 57.41, H 6.85; found: C 57.66, H 6.49.
9-[(4-Methylphenyl)sulfonyl]-3-phenyl-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (16b). Yield: 26%.
M.p. 1788. IR (film): 3033, 2926, 2858, 1721, 1599, 1494, 1459, 1360, 1333, 1234, 1165, 1079, 1040, 994, 965.
1H-NMR (300 MHz, CDCl3): 1.88 (t, J ¼ 5.7. NCH2CH2); 2.43 (s, Me); 2.66 (t, J ¼ 5.7, NCH2CH2); 3.13 (t,
J ¼ 5.7, NCH2CH2); 3.22 (t, J ¼ 5.7, NCH2CH2); 6.63 (s, OCHO); 7.28 – 7.50 (m, 7 arom. H); 7.63 – 7.66
(m, 2 arom. H). 13C-NMR (75.5 MHz, CDCl3): 21.5; 29.7; 31.1; 42.0; 43.1; 106.0; 108.1; 127.4; 127.6; 128.8;
129.8; 130.8; 131.3; 132.9; 143.9. ESI-MS: 392.1 (24, [M þ H]þ). Anal. calc. for C19H21NO6S (391.44): C
58.30, H 5.41, N 3.58; found: C 58.61, H 5.72, N 3.40.
3-(4-Methylphenyl)-9-[(4-methylphenyl)sulfonyl]-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (16c).
Yield: 32%. M.p. 1718. IR (film): 2950, 2924, 1458, 1345, 1331, 1232, 1181, 1156, 1077, 1039, 1017, 995,
729. 1H-NMR (300 MHz, CDCl3): 1.87 (t, J ¼ 6.0, NCH2CH2); 2,36 (s, Me); 2.43 (s, Me); 2.65 (t, J ¼ 6.0,
NCH2CH2); 3.12 (t, J ¼ 6.0, NCH2CH2); 3.22 (t, J ¼ 6.0, NCH2CH2); 6.59 (s, OCHO); 7.18 – 7.22 (m, 2
arom. H); 7.28 – 7.41 (m, 4 arom. H); 7.63 – 7.66 (m, 2 arom. H). HR-ESI-MS: 405.2570 (75, Mþ,
C20H23NO6Sþ; calc. 405.1246).

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Helvetica Chimica Acta – Vol. 95 (2012)
3-(3-Methylphenyl)-9-[(4-methylphenyl)sulfonyl]-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (16d).
Yield: 27%. M.p. 1518. IR (film): 2928, 2865, 1597, 1466, 1358, 1334, 1235, 1167, 1081, 1040, 993, 964,
936. 1H-NMR (300 MHz, CDCl3): 1.85 (t, J ¼ 5.7, NCH2CH2); 2.35 (s, Me); 2.43 (s, Me); 2.63 (t, J ¼ 5.7,
NCH2CH2); 3.10 (t, J ¼ 5.7, NCH2CH2); 3.20 (t, J ¼ 5.7, NCH2CH2); 6.59 (s, OCHO); 7.18 – 7.27 (m, 2
arom. H); 7.28 – 7.41 (m, 4 arom. H); 7.63 – 7.66 (m, 2 arom. H). 13C-NMR (75.5 MHz, CDCl3): 21.2; 29.7;
31.1; 42.0; 43.1; 105.9; 108.2; 124.6; 127.6;127.9; 128.6; 129.8; 132.1; 132.9; 138.9; 138.7; 143.9. HR-ESI-
MS: 405.2080 (85, Mþ, C20H23NO6Sþ; calc. 405.1246).
3-(2-Methylphenyl)-9-[(4-methylphenyl)sulfonyl]-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (16e).
Yield: 27%. M.p. 1678. IR (film): 2924, 2845, 1610, 1358, 1202, 1018, 1007, 911, 835, 797. 1H-NMR
(300 MHz, CDCl3): 1.88 (t, J ¼ 5.7, NCH2CH2); 2.36 (s, Me); 2.38 (s, Me); 2.65 (t, J ¼ 5.7, NCH2CH2); 3.15
(t, J ¼ 5.7, NCH2CH2); 3.25 (t, J ¼ 5.7, NCH2CH2); 6.58 (s, OCHO); 7.18 – 7.28 (m, 3 arom. H); 7.38 – 7.41
(m, 1 arom. H); 7.52 – 7.64 (m, 2 arom. H); 7.76 – 7.78 (m, 2 arom. H). ESI-MS: 406.3 (30, [M þ H]þ).
3-(4-Ethylphenyl)-9-[(4-methylphenyl)sulfonyl]-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (16f).
Yield: 32%. M.p. 1818. IR (film): 2928, 1600, 1458, 1331, 1232, 1156, 1077, 1039, 993, 833, 729.
1H-NMR (300 MHz, CDCl3): 1.21 (t, J ¼ 7.5, MeCH2); 1.87 (t, J ¼ 5.7, NCH2CH2); 2.43 (s, Me); 2.61 –
2.69 (m, 4 H); 3.12 (t, J ¼ 6.0, NCH2CH2); 3.22 (t, J ¼ 5.7, NCH2CH2); 6.59 (s, OCHO); 7.20 (d, J ¼
8.1, 2 arom. H); 7.28 – 7.34 (m, 4 arom. H); 7.63 – 7.66 (d, J ¼ 8.1, 2 arom. H). ESI-MS: 420.1 (55, [M þ
H]þ). Anal. calc. for C21H25NO6S (419.49): C 60.13, H 6.01, N 3.34; found: C 59.85, H 6.35, N 3.63.
9-[(4-Methylphenyl)sulfonyl]-3-(4-propylphenyl)-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (16g).
Yield: 21%. M.p. 1688. IR (film): 2929, 2363, 1653, 1542, 1522, 1459, 1360, 1156, 1018, 909, 792.
1H-NMR (300 MHz, CDCl3): 0.88 (t, J ¼ 7.2, MeCH2CH2); 1.55 – 1.67 (m, MeCH2CH2); 1.86 (t, J ¼ 5.7,
NCH2CH2); 2.43 (s, Me); 2.56 – 2.66 (m, MeCH2CH2, NCH2CH2); 3.12 (t, J ¼ 5.7, NCH2CH2); 3.22 (t, J ¼
5.7, NCH2CH2); 6.59 (s, OCHO); 7.18 (d, J ¼ 8.1, 2 arom. H); 7.25 – 7.33 (m, 4 arom. H); 7.63 (d, J ¼ 8.1, 2
arom. H). 13C-NMR (75.5 MHz, CDCl3): 13.7; 21.5; 24.3; 29.7; 30.3; 31.1; 37.9; 42.0; 43.1; 105.9; 108.2;
127.4; 127.6; 128.2; 128.9; 129.8; 133.0; 143.9; 146.4. ESI-MS: 434.1 (60, [M þ H]þ). Anal. calc. for
C22H27NO6S (433.52): C 60.95, H 6.28, N 3.23; found: C 60.62, H 6.04, N, 3.40.
9-[(4-Methylphenyl)sulfonyl]-3-[4-(propan-2-yl)phenyl]-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane
(16h). Yield: 27%. M.p. 1788 IR (film): 2951, 1602, 1369, 1017, 1018, 1002, 922, 756. 1H-NMR (300 MHz,
CDCl3): 1.21 (d, J ¼ 6.9, Me2CH); 1.85 – 1.89 (m, NCH2CH2); 2.43 (s, Me); 2.65 – 2.67 (m, NCH2CH2);
2.86 – 2.95 (sept., Me2CH), 3.12 (t, J ¼ 5.7, NCH2CH2); 3.22 (t, J ¼ 5.7, NCH2CH2); 6.59 (s, OCHO); 7.23 –
7.34 (m, 6 arom. H); 7.63 – 7.66 (m, 2 arom. H). ESI-MS: 434.1 (25, [M þ H]þ).
3-[4-(tert-Butyl)phenyl]-9-[(4-methylphenyl)sulfonyl]-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane
(16i). Yield: 40%. M.p. 1968. IR (film): 2959, 2925, 2855, 1345, 1331, 1232, 1181, 1156, 1077, 1039, 994, 965.
1H-NMR (300 MHz, CDCl3): 1.29 (s, Me3C); 1.87 (t, J ¼ 5.7, NCH2CH2); 2.43 (s, Me); 2.65 (t, J ¼ 5.7,
NCH2CH2); 3.12 (t, J ¼ 5.7, NCH2CH2); 3.22 (t, J ¼ 5.7, NCH2CH2); 6.60 (s, OCHO); 7.30 – 7.34 (m, 4
arom. H); 7.40 – 7.45 (m, 2 arom. H); 7.63 – 7.66 (m, 2 arom. H). 13C-NMR (75.5 MHz, CDCl3): 21.5; 29.7;
31.1; 34.8; 42.0; 43.1; 105.8; 108.0; 125.7; 127.7; 127.2; 127.6; 127.9; 129.8; 132.9; 143.8; 154.7. ESI-MS:
448.2 (100, [M þ H]þ). Anal. calc. for C23H29NO6S (447.54): C 61.72, H 6.53, N 3.13; found: C 61.91, H
6.88, N 3.35.
3-(4-Fluorophenyl)-9-[(4-methylphenyl)sulfonyl]-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (16k).
Yield: 40%. M.p. 1758. IR (film): 3038, 2926, 2857, 1601, 1460, 1328, 1232, 1077, 1038, 1015, 993.
1H-NMR (300 MHz, CDCl3): 1.87 (t, J ¼ 5.7, NCH2CH2); 2.43 (s, Me); 2.61 – 2.69 (m, NCH2CH2); 3.12 (t,
J ¼ 5.7, NCH2CH2); 3.22 (t, J ¼ 5.7, NCH2CH2); 6.59 (s, OCHO); 7.20 (d, J ¼ 8.1, 2 arom. H); 7.28 – 7.34
(m, 4 arom. H); 7.63 (d, J ¼ 8.1, 2 arom. H). ESI-MS: 410.1 (22, [M þ H]þ). Anal. calc. for C19H20FNO6S
(409.43): C 55.74, H 4.92, N 3.42; found: C 55.53, H 4.74, N, 3.66.
3-(4-Bromophenyl)-9-[(4-methylphenyl)sulfonyl]-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (16l).
Yield: 27%. M.p. 1678. IR (film): 2922, 2847, 1611, 1357, 1212, 1018, 1017, 911, 835, 797. 1H-NMR
(300 MHz, CDCl3): 1.87 (t, J ¼ 5.7, NCH2CH2); 2.44 (s, Me); 2.63 (t, J ¼ 5.7, NCH2CH2); 3.12 (t, J ¼ 5.7,
NCH2CH2); 3.22 (t, J ¼ 5.7, NCH2CH2); 6.59 (s, OCHO); 7.26 – 7.39 (m, 4 arom. H); 7.53 – 7.66 (m, 4 arom.
H). ESI-MS: 471.0 (100, [M þ H]þ), 472.1 (95). Anal. calc. for C19H20BrNO6S (470.33): C 48.52, H 4.29,
N 2.98; found: C 48.73, H 4.49, N 3.18.
3-(3-Bromophenyl)-9-[(4-methylphenyl)sulfonyl]-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (16m).
Yield: 23%. M.p. 1478. IR (film): 2963, 2862, 1722, 1597, 1573, 1468, 1427, 1358, 1263, 1236, 1164, 1079,

Helvetica Chimica Acta – Vol. 95 (2012)
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1021, 935. 1H-NMR (300 MHz, CDCl3): 1.80 (t, J ¼ 5.7, NCH2CH2); 2.37 (s, Me); 2.56 (t, J ¼ 5.7,
NCH2CH2); 3.05 (t, J ¼ 5.7, NCH2CH2); 3.15 (t, J ¼ 5.7, NCH2CH2); 6.52 (s, OCHO); 7.19 – 7.27 (m, 5
arom. H); 7.45 – 7.59 (m, 3 arom. H). Anal. calc. for C19H20BrNO6S (470.33): C 48.52, H 4.29, N 2.98;
found: C 48.52, H 4.29, N, 2.98.
3-(4-Methylphenyl)-9-(phenylsulfonyl)-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (17a). Yield: 26%.
M.p. 1788. IR (film): 3069, 2961, 2930, 2868, 1612, 1445, 1330, 1233, 1162, 1077, 1039, 993. 1H-NMR
(300 MHz, CDCl3): 1.88 (t, J ¼ 5.7, NCH2CH2); 2.42 (s, Me); 2.65 (t, J ¼ 5.7, NCH2CH2); 3.15 (t, J ¼ 5.7,
NCH2CH2); 3.25 (t, J ¼ 5.7, NCH2CH2); 6.58 (s, OCHO); 7.18 – 7.28 (m, 3 arom. H); 7.38 – 7.41 (m, 2 arom.
H); 7.52 – 7.64 (m, 2 arom. H); 7.76 – 7.78 (m, 2 arom. H). HR-ESI-MS: 391.9906 (Mþ, C19H21NO6Sþ; calc.
391.1090).
3-(3-Methylphenyl)-9-(phenylsulfonyl)-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (17b). Yield: 31%.
M.p. 1438. IR (film): 3029, 2927, 2866, 1466, 1447, 1360, 1334, 1268, 1235, 1171, 1097, 1081, 1042, 1015, 991.
1H-NMR (300 MHz, CDCl3): 1.89 (t, J ¼ 5.7, NCH2CH2); 2.42 (s, Me); 2.66 (t, J ¼ 5.7, NCH2CH2); 3.15 (t,
J ¼ 5.7, NCH2CH2); 3.25 (t, J ¼ 5.7, NCH2CH2); 6.81 (s, OCHO); 7.18 – 7.34 (m, 4 arom. H); 7.52 – 7.64 (m,
3 arom. H); 7.76 – 7.79 (m, 2 arom. H).13C-NMR (75.5 MHz, CDCl3): 18.8; 29.9; 31.1; 42.0; 43.6; 105.9;
126.2; 127.5; 129.2; 130.8; 131.0; 133.0. HR-ESI-MS: 391.2341 (Mþ, C19H21NO6Sþ; calc. 391.1090).
3-(2-Methylphenyl)-9-(phenylsulfonyl)-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (17c). Yield: 23%.
M.p. 1638. IR (film): 2922, 2852, 1637, 1363, 1217, 1018, 1003, 804, 775. 1H-NMR (300 MHz, CDCl3): 1.87
(t, J ¼ 5.4, NCH2CH2); 2.42 (s, Me); 2.65 (t, J ¼ 5.4, NCH2CH2); 3.13 (t, J ¼ 5.4, NCH2CH2); 3.23 (t, J ¼
5.4, NCH2CH2); 6.81 (s, OCHO); 7.18 – 7.34 (m, 4 arom. H); 7.52 – 7.64 (m, 3 arom. H); 7.76 – 7.79 (m, 2
arom. H). ESI-MS: 392.1 (24, [M þ H]þ). Anal. calc. for C19H21NO6S (391.44): C 58.30, H 5.41, N 3.58;
found: C 58.51, H 5.66, N 3.76.
3-(4-Ethylphenyl)-9-(phenylsulfonyl)-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (17d). Yield: 33%.
M.p. 1508. IR (film): 3069, 2961, 1930, 1868, 1612, 1445, 1329, 1272, 1233, 1162, 1077, 1039, 993. 1H-NMR
(300 MHz, CDCl3): 1.21 (t, J ¼ 6.0, MeCH2); 1.88 (m, NCH2CH2); 2.64 – 2.66 (m, NCH2CH2, MeCH2);
3.15 – 3.42 (m, 2 NCH2CH2); 6.59 (s, OCHO); 7.21 – 7.30 (m, 4 arom. H); 7.54 – 7.61 (m, 3 arom. H); 7.76 –
7.78 (m, 2 arom. H). 13C-NMR (75.5 MHz, CDCl3): 15.3; 28.8; 29.7; 31.1; 42.0; 43.1; 105.8; 108.2; 127.5;
128.3; 129.2; 133.0; 136.0; 148.0. HR-ESI-MS: 405.8187 (78, Mþ, C20H23NO6Sþ; calc. 405.1246).
9-(Phenylsulfonyl)-3-(4-propylphenyl)-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (17e). Yield: 26%.
1
M.p. 1428. IR (film): 2954, 2870, 1446, 1332, 1233, 1168, 1077, 1040, 994, 897, 740. H-NMR (300 MHz,
CDCl3): 0.91 (t, J ¼ 7.5, MeCH2CH2); 1.56 – 1.67 (m, MeCH2CH2); 1.87 (t, J ¼ 5.7, NCH2CH2); 2.58 (t, J ¼
7.5, MeCH2CH2); 2.65 (t, J ¼ 5.7, NCH2CH2); 3.15 (t, J ¼ 5.7, NCH2CH2); 3.25 (t, J ¼ 5.7, NCH2CH2); 6.59
(s, OCHO); 7.18 (d, J ¼ 8.1, 2 arom. H); 7.28 (d, J ¼ 8.1, 2 arom. H); 7.51 – 7.64 (m, 3 arom. H); 7.76 – 7.78
(m, 2 arom. H). 13C-NMR (75.5 MHz, CDCl3): 13.6; 24.2; 29.7; 31.1; 37.8; 42.0; 43.1; 105.8; 108.2; 127.4;
127.5; 128.8; 129.2; 133.0; 136.0; 146.4. HR-ESI-MS: 419.8205 (Mþ, C21H25NO6Sþ; calc. 419.1403).
9-(Phenylsulfonyl)-3-[4-(propan-2-yl)phenyl]-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (17f).
Yield: 21%. M.p. 1678. IR (film): 2956, 2925, 1459, 1331, 1233, 1161, 1076, 1039, 1015, 992, 965.
1H-NMR (300 MHz, CDCl3): 1.23 (d, J ¼ 6.9, Me2CH); 1.88 (t, J ¼ 5.7, NCH2CH2); 2.66 (t, J ¼ 5.7,
NCH2CH2); 2.88 – 2.95 (sept., Me2CH); 3.15 (t, J ¼ 5.7, NCH2CH2); 3.25 (t, J ¼ 5.7, NCH2CH2); 6.59 (s,
OCHO); 7.23 – 7.32 (m, 4 arom. H); 7.52 – 7.64 (m, 3 arom. H); 7.76 – 7.79 (m, 2 arom. H). ESI-MS: 420.14
(100, [M þ H]þ).
3-[4-(tert-Butyl)phenyl]-9-(phenylsulfonyl)-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (17g). Yield:
22%. M.p. 1738. IR (film): 2959, 2925, 2852, 1607, 1457, 1360, 1170, 1080, 1041, 994. 1H-NMR (300 MHz,
CDCl3): 1.29 (s, Me3C); 1.88 (t, J ¼ 5.7, NCH2CH2); 2.66 (t, J ¼ 5.7, NCH2CH2); 3.15 (t, J ¼ 5.7,
NCH2CH2); 3.25 (t, J ¼ 5.7, NCH2CH2); 6.60 (s, OCHO); 7.30 – 7.33 (m, 2 arom. H); 7.40 – 7.45 (m, 3 arom.
H); 7.54 – 7.62 (m, 2 arom. H); 7.76 – 7.79 (m, 2 arom. H). ESI-MS: 434.1 (85, [M þ H]þ). Anal. calc. for
C22H27NO6S (433.52): C 60.95, H 6.28, N 3.23; found: C 61.17, H 6.44, N 3.21.
3-(4-Methoxyphenyl)-9-(phenylsulfonyl)-1,2,4,5-tetraoxa-9-azaspiro[5.5]undecane (17h). Yield:
21%. M.p. 1808. IR (film): 2924, 2850, 1610, 1517, 1359, 1333, 1309, 1256, 1170, 1080, 1041, 991.
1H-NMR (300 MHz, CDCl3): 1.87 (t, J ¼ 5.7, NCH2CH2); 2.65 (t, J ¼ 5.7, NCH2CH2); 3.15 (t, J ¼ 5.7,
NCH2CH2); 3.25 (t, J ¼ 5.7, NCH2CH2); 3.81 (s, MeO); 6.55 (s, OCHO); 6.88 (d, J ¼ 8.7, 2 arom. H); 7.30
(d, J ¼ 8.7, 2 arom. H); 7.53 ꢀ 7.64 (m, 3 arom. H); 7.76 – 7.79 (m, 2 arom. H).13C-NMR (75.5 MHz,

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Helvetica Chimica Acta – Vol. 95 (2012)
CDCl3): 29.8; 31.1; 42.1; 43.1; 55.3; 105.6; 108.0; 114.2; 123.08; 127.5; 129.2; 129.2; 133.0; 136.1; 161.9. HR-
ESI-MS: 407.6611 (Mþ, C19H21NO7Sþ; calc. 407.1039).
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Received January 12, 2012