2-Sulfonyliminodihydropyrimidines: A novel class of analgesic compounds

Article abstract of DOI:10.1002/ardp.200800107

A series of 2-sulfonyliminodihydropyrimidine derivatives have been synthesized and evaluated in vivo for their antinociceptive and anti-inflammatory activities. The results were compared with that of acetyl salicylic acid. Compounds 6Ab-d and 6Be displaye

Full text of DOI:10.1002/ardp.200800107

690
Arch. Pharm. Chem. Life Sci. 2008, 341, 690–695
Full Paper
2-Sulfonyliminodihydropyrimidines: A Novel Class of
Analgesic Compounds
M. Eugenia Gonzꢀlez-Rosende1, Teresa Olivar2, Encarna Castillo2, and Josꢁ Sepffllveda-Arques3
1 Department of Chemistry, Biochemistry and Molecular Biology, University CEU Cardenal Herrera, Moncada,
Valencia, Spain
2 Department of Physiology, Pharmacology and Toxicology, University CEU Cardenal Herrera, Moncada,
Valencia, Spain
3 Department of Organic Chemistry, University of Valencia, Burjassot, Valencia, Spain
A series of 2-sulfonyliminodihydropyrimidine derivatives have been synthesized and evaluated
in vivo for their antinociceptive and anti-inflammatory activities. The results were compared
with that of acetyl salicylic acid. Compounds 6Ab–d and 6Be displayed an interesting analgesic
profile in the acetic acid-induced abdominal contractions test. Based on the results of the carra-
geenan-hind paw edema test, compound 6Af showed potential anti-inflammatory activity.
Keywords: Anti-inflammatory activity / Antinociceptive activity / Dihydropyrimidines /
Received: June 9,2008; accepted: July 3, 2008
DOI 10.1002/ardp.200800107
their analgesic and anti-inflammatory activities (Scheme
1).
Introduction
Various types of heterocyclic compounds have been syn-
thesized in the search for more effective and safer drugs
[1]. In this context, pyrimidine derivatives with analgesic
and anti-inflammatory activity have been reported in the
literature [2–9]. Although there is a large amount of
experimental work on this heterocyclic system, it still
remains an area of active research.
In the course of an ongoing research project aimed at
the synthesis and pharmacological evaluation of new bio-
active compounds, we previously described the anti-
inflammatory profile of imidazo[1,2-a]pyrimidines 1 [10],
imidazo[1,2-c]pyrimidines 2 [11], and tosyldihydropyrimi-
dine derivatives 3 [12]. Compounds from series 2, particu-
larly the p-fluoro derivative 2a, showed a interesting anti-
inflammatory activity when administered to mice orally.
As continuation of our research program on the syn-
thesis of heterocyclic systems exhibiting biological activ-
ity, we designed the pyrimidine derivatives 6 employing
the molecular simplification strategy, and we evaluated
Results and discussion
The pyrimidine derivatives 6 were prepared according to
the literature procedure [13]. Reaction of 2-sulfonylami-
nopyrimidines 4A, B with the appropriate iodocarboxa-
mide 5a–g in the presence of Hꢀnig's base in DMF pro-
vided the corresponding 2-tosylimino-1-substituted dihy-
dropyrimidines 6Aa–g and 2-mesyliminodihydropyrimi-
dines 6Bd, e. In some cases, pyrimidines 7 were obtained
along with dihydropyrimidines 6 (Scheme 2).
As it is outlined in Table 1, higher yields of compounds
6 resulting from the pyrimidine nitrogen alkylation
were obtained in comparison with compounds 7 from
the exocyclic nitrogen alkylation. In some cases, com-
pounds 7 were not even detected. These results are in
accordance with the literature [14, 15].
The antinociceptive activity of compounds 6Aa–g and
6Bd, e was evaluated in mice intraperitoneally (i.p.) in
two different noxious stimuli: acetic acid writhing test
[16] and hot plate test [17] as a measure of peripheral and
central acute pain, respectively. In the writhing test, the
2-sulfonyliminodihydropyrimidines 6Ab–d and 6Be dis-
Correspondence: Dr. M. Eugenia Gonzꢀlez-Rosende, University CEU
Cardenal Herrera, Edificio Seminario s/n, 46113-Moncada, Valencia,
Spain.
E-mail: eugenia@uch.ceu.es
Fax: +34 961 395 272
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Arch. Pharm. Chem. Life Sci. 2008, 341, 690–695
2-Sulfonyliminodihydropyrimidines as Analgesic Compounds
691
Scheme 1. Imidazopyrimidines 1 and 2 and sulfonyldihydropyrimidine 3 and 6 derivatives.
Scheme 2. Synthesis of compounds 6 and 7.
Figure 1. Effect of compounds 6Ab–6Ad and 6Be on acetic
acid-induced writhing test in mice. Groups of 6-24 mice received
acetic acid (0.1 mL/10 g, i.p., 0.6%) 30 min after administration
of the compounds. Data represent mean l SEM, * P a0.05 and
** P a0.01.
Table 1. Yields obtained in the preparation of sulfonylpyrimi-
dines 6 and 7.
R
R9
R99
6 (%)
7 (%)
p-CH3C6H5
p-CH3Ph
p-CH3Ph
p-CH3Ph
p-CH3Ph
p-CH3Ph
p-CH3Ph
CH3
H
H
H
H
6Aa (85)
6Ab (80)
6Ac (70)
6Ad (50)
6Ae (90)
6Af (71)
6Ag (90)
6Bd (70)
6Be (72)
7Aa (–)
7Ab (–)
7Ac (–)
7Ad (10)
7Ae (–)
7Af (12)
7Ag (–)
7Bd (20)
7Be (18)
6Be at the dose of 50 mg/kg, whereas this compound was
not effective at the lowest dose (1 mg/kg). Compounds
6Ae and 6Bd significantly inhibited the response, but
this effect was not dose-dependent. Finally, compounds
6Aa, 6Af, and 6Ag did not show any effect. In the hot
plate test, no antinociceptive effect was observed for any
of the compounds.
Ph
p-FPh
H
H
H
o-ClPh
H
H
p-HOPh
p-BrPh
Ph
H
p-HOPh
p-BrPh
CH3
As regards to the anti-inflammatory activity the behav-
ior of the sulfonyliminodihydropyrimidines 6 was differ-
ent. The anti-inflammatory effect of compounds 6Ac, d,
6Af, and 6Bd was tested by the carrageenan hind paw
edema assay [18]. It was found that among the com-
pounds examined, the only compound that significantly
inhibited formation of edema was 6Af, having a phenyl
group on the carboxamide moiety (Fig. 2). The inhibition
of the edema produced by this compound was significant
2, 3, and 5 hours after the intraplantar administration of
carrageenan.
played an interesting analgesic profile. These four com-
pounds showed a dose–dependet effect with significant
decrease of the number of writhing movements (Fig. 1).
The results of the nociceptive experiments are shown
in Table 2. The percentage of inhibition was calculated
from the difference in the writhing response between
the treated and the control group (vehicle). Acetylsali-
cylic acid was used as a reference substance in the experi-
ments. Compounds 6Ab–d inhibited significantly the
response to the acetic acid at all doses tested. The highest
percent of inhibition (83.9%) was shown by compound
Due to the small number of compounds evaluated and
the diversity of types involved, it does not seem reason-
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692
M. E. Gonzꢀlez-Rosende et al.
Arch. Pharm. Chem. Life Sci. 2008, 341, 690–695
a substituent on the C carboxamide moiety could be con-
sidered as the open ring analogous of the imidazo [1,2-
c]pyrimidines 2. In addition, it is interesting to note the
presence of a p-fluoro substituent in compound 6Ac simi-
larly to the imidazo[1,2-c]pyrimidine derivative 2a
(Scheme 1). The displacement of the phenyl ring to the N-
carboxamide moiety led to 6Ad–f and 6Bd, e. In this ser-
ies, most of the compounds showed a fairly good activity.
The p-bromo mesyl derivative 6Be exhibited stronger
antinociceptive activity than the corresponding tosyl
derivative 6Ae, whereas in the case of the p-hydroxy
derivatives, which could be considered structurally
related to p-acetaminophen, the compound 6Bd with the
mesyl group was less active than the tosylated 6Ad. Thus,
the influence of the sulfonyl substituent toward the anti-
nociceptive activity cannot be clearly expressed.
In summary, we report on the synthesis and evaluation
of the antinociceptive and anti-inflammatory activities
of sulfonyliminodihydropyrimidine derivatives. In-vivo
evaluation of compounds 6 has shown that exhibit inter-
esting pharmacological properties when administered
by the intra-peritoneal route. These preliminary results
indicate a test and structure dependent antinociceptive
responses for the 2-tosyliminodihydropyrimidine deriv-
atives 6A and 2-mesyliminodihydropyrimidine deriv-
atives 6B. No clear-cut relationship could be recognized
between pharmacological activities and chemical struc-
ture. Synthesis and pharmacological evaluation of
related 2-sulfonyliminodihydropyrimidines to deter-
mine structural features for the antinociceptive and anti-
inflammatory activities are in progress.
Figure 2. Effect of compounds 6Ac, d, f and 6Bd (50 mg/kg,
i.p.), 30 min, 1 h, 2 h, 3 h, and 5 h after intraplantar carrageenan
injection (0.1 mL; 2%). Data represent mean l SEM, * P a0.05 (n
= 9–12).
Table 2. Effects of compounds 6Aa–g and 6Bd, e on the num-
ber of writhing movements induced by acetic acid (0.6%, i.p.) in
mice (n = 6–24). Data are presented as row data and as per-
centage of inhibition.
Compound
Dosea) (mg/kg) Number of
writhing move-
Inhibition (%)b)
ments
Vehicle
AAS
6Aa
46.7 l 2.3
2.4 l 0.3
89.8**
3.2
–19.4
24.1
1
10
50
1
10
50
1
10
50
1
10
50
1
10
50
1
10
50
1
10
50
1
10
50
1
45.2 l 7.0
55.8 l 7.7
35.4 l 7,2
26.5 l 4.1*
23.6 l 6.0*
18.0 l 6.3*
14.8 l 2.3*
11.0 l 2.3**
10.0 l 2.8**
32.5 l 5.0*
31.2 l 5.9*
11.1 l 3.3**
29.0 l 1.2*
31.0 l 2.9*
31.0 l 2.6*
46.3 l 5.8
43.2 l 6.1
38.1 l 7.1
39.8 l 8.0
32.8 l 12.7
29.2 l 5.6
30.0 l 3.3*
33.5 l 2.9*
31.3 l 2.0*
46.0 l 9.3
22.8 l 8.5*
7.5 l 2.4**
6Ab
6Ac
6Ad
6Ae
6Af
6Ag
6Bd
6Be
43.3*
49.5*
61.5*
68.3*
76.4**
78.6**
30.4*
33.3*
76.2**
37.9*
33.6*
33.6*
0.9
We are indebted to the Generalitat Valenciana (Project GV05/
139) for financial support.
The authors have declared no conflict of interest.
7.5
18.4
14.9
29.8
37.5
Experimental
35.8*
28.3*
32.9*
1.5
51.3*
83.9**
Chemistry
All reagents were purchased from Aldrich (Sigma-Aldrich,
Madrid, Spain) and used without purification unless stated oth-
erwise. All experiments were carried out under nitrogen atmos-
phere. Melting points were determined with a Kofler hot-stage
apparatus (C. Reichert, Vienna, Austria) and are uncorrected.
Flash column chromatography was performed using silica gel
(Merck 60, 70–230 mesh; Merck, Germany). 1H- and 13C-NMR
spectra were recorded on a Bruker AC-300 instrument (Bruker
BioScience, Billerica, MA, USA) unless otherwise indicated.
Chemical shifts (d values) and coupling constants (J values) are
given in ppm and Hz respectively. HRMS were obtained using a
VG Autospec TRIO 1000 instrument (Fisons, Manchester, UK).
The ionization mode used in mass spectra was electron impact
10
50
a)
All compounds were administered i.p.
%-inhibition obtained by comparison with vehicle group.
b)
* P a0.05.
** P a0.01. Results are expressed as mean l SEM
able to attempt to analyze the structure-activity relation-
ship (SAR), although several comparisons on the results
could be made. Compounds 6Ab, c with a phenyl ring as
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Arch. Pharm. Chem. Life Sci. 2008, 341, 690–695
2-Sulfonyliminodihydropyrimidines as Analgesic Compounds
693
1
(EI) or fast atom bombardment (FAB). H- and 13C-NMR assign-
air dried, and purified by flash column chromatography to give
the exocyclic nitrogen alkylated compounds 7 (hexane : EtOAc
1 : 1) and the endocyclic nitrogen alkylated compounds 6
(EtOAc:MeOH 9 : 1).
ments have been confirmed by homonuclear two dimensional
correlations and DEPT experiments. Compounds 6Aa–c and 6Ag
were prepared as described in the literature [13].
N-(4-Hydroxyphenyl)-2-[{[(4-
General Procedure for the synthesis of 2-
methylphenyl)sulfonyl]imino}pyrimidin-1(2H)-
(sulfonamido)pyrimidines 4A, B
To a solution of 2-aminopyrimidine (20 mmol) in dry pyridine
(8 mL) at 08C was slowly added the corresponding sulfonyl chlor-
ide (30 mmol) in pyridine (6 mL) The solution was stirred for 2 h
and allowed to reach room temperature. Water was added
(100 mL) and the solid was collected and recrystallized.
yl]acetamide 6Ad
Yield: 50%; m.p.: 221–2238C; 1H-NMR (300 MHz, DMSO-d6): 2.3 (s,
3H), 4.89 (s, 2H), 6.72 (d, J = 9 Hz, 2H), 6.87 (dd, J = 4.5 Hz, J = 6 Hz,
1H), 7.15 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 9 Hz, 2H), 7.64 (d, J = 8.4 Hz,
2H), 8.41 (dd, J = 2.4 Hz, J = 6 Hz), 8.64 (dd, J = 2.4 Hz, J = 4.5 Hz,
1H), 10.25 (br, 1H, NH or OH); 13C-NMR (75 MHz, DMSO-d6): 21.2
(CH3), 48.9 (CH2), 108.1 (CH), 115.5 (CH), 121.2 (CH), 126.9 (CH),
128.9 (CH), 130.5 (C), 141.2 (C), 141.3 (C), 152.0 (CH), 153.9 (C),
154.6 (C), 163.6 (CO), 164.8 (CH); HRMS (EI+) m/z calcd for
C19H19N4O4S1: 399.1127; found: 399.1127.
2-(p-Toluenesulfonamido)pyrimidine 4A
Recrystallized from chloroform. Yield 90%; m.p.: 208–2108C (lit
[13] 204–2068C).
2-Methanesulfonamidopyrimidine 4B
N1-(4-Hydroxyphenyl)-N2-[(4-methylphenyl)sulfonyl]-N2-
Yield: 65%; m.p.: 258.6–2608C. 1H-NMR (300 MHz, DMSO-d6): 3.36
(s, 3H), 7.13 (t, J = 4.9 Hz, 1H), 8.61 (d, J = 4.9 Hz, 2H), 11.33 (br,
1H); 13C-NMR (75 MHz, DMSO-d6) 41.6 (CH3), 40.5 (CH2), 116.1(CH),
117.9 (C), 158.9 (CH).
pyrimidin-2-ylglycinamide 7Ad
1
Yield: 10%; m.p.: 168–1738C; H-NMR (300 MHz, DMSO-d6): 2.39
(s, 3H), 4.91 (s, 2H), 6.66 (d, J = 9 Hz, 2H), 7.01 (t, J = 4.8 Hz, 1H),
7.32 (d, J = 7.95 Hz, 2H), 7.34 (d, J = 7.5 Hz, 2H), 8.0 (d, J = 9 Hz, 2H),
8.47 (d, J = 4.5 Hz, 2H), 9.2 (br, 1H). 10.01 (s, 1H); 13C-NMR
(75 MHz, DMSO-d6): 21.4 (CH3), 48.7 (CH2), 115.5 (CH), 116.3 (CH),
121.1 (CH), 128.9 (CH), 129.3 (CH), 130.9 (C), 137.8 (C), 143.9 (C),
153.7 (C), 157.7 (C), 158.1 (CH), 165.7 (CO).
General procedure for the synthesis of iodoacetamides
5d–f [19]
Powdered KI (5 mmol) was added to a solution of the correspond-
ing chlorocarboxamide (1 mmol) in dry acetone (1 mL). The reac-
tion mixture was refluxed for 8 h and filtered. The solvent was
evaporated and the residue was used without further purifica-
tion.
N-(4-Bromophenyl)-2-[{[(4-
methylphenyl)sulfonyl]imino}pyrimidin-1(2H)-
yl]acetamide 6Ae
Yield: 90%; m.p.: 274.8–275.28C; 1H-NMR (DMSO-d6): 2.4 (s, 3H),
4.93 (s, 2H), 6.89 (dd, J = 4.2 Hz, J = 6.3, 1H), 7.14 (d, J = 8.1 Hz, 2H),
7.55 (s, 4H), 7.62 (d, J = 8.1 Hz, 2H), 8.42 (dd, J = 2.4 Hz, J = 6.3 Hz,
1H), 8.67 (dd, J = 2.4 Hz, J = 4.2 Hz, 1H), 10.64 (s, 1H, NH); 13C-NMR
(75 MHz, DMSO-d6): 21.3 (CH3), 55.9 (CH2), 108.2 (CH), 115.6 (C),
121.3 (CH), 126.9 (CH), 128.9 (CH), 132.1 (CH), 138.3 (C), 141.0 (C),
141.3 (C), 151.1 (CH), 154.5 (C), 165.0 (CO), 165.5 (CH); HRMS (EI+)
m/z calcd for C19H17BrN4O3S: 460.0205; found: 460.0207.
N-(4-Hydroxyphenyl)-2-iodoacetamide 5d
Yield: 80%; m.p.: 155–1578C (lit [19] 1538C); 1H-NMR (300 MHz,
DMSO-d6): 3.7 (s, 2H), 6.6 (d, J = 7.8 Hz, 2H), 7.3 (d, J = 8.2 Hz, 2H),
9.1 (br, 1H, OH), 9.8 (s, 1H, NH); 13C-NMR (75 MHz, DMSO-d6): 0.1
(CH2), 113.3 (CH), 118.9 (CH) 128.6 (C), 151.7 (C), 163.8 (CO).
N-(4-Bromophenyl)-2-iodoacetamide 5e
Yield: 90%; m.p.: 179–1808C (lit [20] 182–1848C); 1H-NMR
(300 MHz, DMSO-d6): 3.75 (s, 2H), 7.45 (m, 4H), 10.4 (s, 1H, NH);
13C-NMR (75 MHz, DMSO-d6): 0.1 (CH2), 114.0 (C), 120.1 (CH), 130.3
(CH), 137.0 (C), 165.4 (CO).
[2-{[(4-Methylphenyl)sulfonyl]imino}pyrimidin-1(2H)-yl]-N-
phenylacetamide 6Af
1
Yield: 71%; m.p.: 240–2448C; H-NMR (300 MHz, DMSO-d6): 2.44
(s, 3H), 4.90 (s, 2H), 6.91 (dd, J = 6.6 Hz, J = 4.51 Hz, 1H), 7.17 (m,
3H), 7.39 (t, J = 7.5 Hz, 2H), 7.62 (d, J = 8.12 Hz, 2H), 7.67 (d, J =
7.5 Hz, 2H), 8.46 (dd, J = 6.6 Hz, J = 2.4 Hz, 1H), 8.7 (dd, J = 4.5 Hz, J
= 2.4 Hz, 1H), 10.53 (s, 1H, NH); 13C-NMR (75 MHz, DMSO-d6): 21.2
(CH3), 55.9 (CH2), 108.1 (CH), 119.4 (CH), 124.0 (C), 126.9 (CH),
128.9 (CH), 129.3 (CH), 138.9 (C), 141.2 (C), 141.3 (C), 152.0 (CH),
154.6 (C), 164.3 (CO), 164.9 (CH); HRMS (EI+) m/z calcd for
C19H18N4O3S: 382.1099; found: 382.1105.
2-Iodo-N-phenylacetamide 5f
Yield: 80%; m.p.: 143–1468C (lit [21] 141–1428C); 1H-NMR
(300 MHz, DMSO-d6): 3.8 (s, 2H), 7.05 (t, J = 7.5 Hz, 1H), 7.3 (t, J =
7.5 Hz, 2H), 7.55 (d, J = 7.5 Hz, 2H), 10.3 (s, 1H, NH); 13C-NMR
(75 MHz, DMSO-d6): 0.2 (CH2), 117.8 (CH), 122.0 (CH), 127.2 (CH),
137.2 (C), 165.0 (CO).
General procedure for the preparation of compounds
6 and 7
N2-[(4-Methylphenyl)sulfonyl]-N1-phenyl-N2-pyrimidin-2-
ylglycinamide 7Af
Diisopropylethylamine, DIPEA (0.65 mL, 3.6 mmol) was added
dropwise to a stirred suspension of 2-sulfonamidopyrimidine 4
(3 mmol) in dry DMF (12 mL) under argon. After 40 min, the cor-
responding iodocarboxamide 5 (3.6 mmol) was added. The reac-
tion mixture was stirred at room temperature for 16 h and then
poured onto water (100 mL). The resulting solid was collected,
Yield: 12%; m.p.: 148–1508C; 1H-NMR (300 MHz, DMSO-d6): 2.88
(s, 3H), 5.00 (s, 2H), 7.07 (m, 2H), 7.34 (t, J = 8.1 Hz, 2H), 7.39 (d, J =
5.4 Hz, 2H), 7.58 (d, J = 7.8 Hz, 2H), 8.05 (d, J = 8.1 Hz, 2H) 8.51 (d, J
= 5.4 Hz, 2H), 10.30 (s, 1H, NH); 13C-NMR (75 MHz, DMSO-d6): 21.8
(CH3 ), 49.5 (CH2 ), 119.9 (CH), 124.1(CH), 126.4 (CH), 129.4 (CH),
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694
M. E. Gonzꢀlez-Rosende et al.
Arch. Pharm. Chem. Life Sci. 2008, 341, 690–695
129.7 (CH), 129.9 (CH), 139.7 (C), 144.5 (C), 154.1 (C), 158.1 (C),
158.7 (CH), 163.2 (CO).
and jumping movements (determined in seconds) were
recorded.
Anti-inflammatory activity
N-(4-Hydroxyphenyl)-2-[(2-
The anti-inflammatory activity was studied in a carrageenan-
induced rat paw oedema test [18]. Female Wistar rats (120–
140 g, n = 9–12) were used. Compounds under evaluation or sal-
ine solution were administered intraperitoneally (50 mg/kg)
30 min before intraplantar injection of 0.1 mL of 2% carra-
geenan solution in saline. The paw volume was measured using
a glass plethysmometer (Ugo Basile, Italy) 30 min, 1h, 2h, 3h,
and 5 hours after carrageenan injection.
[(methylsulfonyl)imino]pyrimidin-1(2H)-yl]acetamide 6Bd
1
Yield: 70%; m.p.: 180–1848C; H-NMR (300 MHz, DMSO-d6): 2.95
(s, 3H), 4.91 (s, 2H), 6.71 (d, J = 9 Hz, 2H), 6.91 (dd, J = 4.2 Hz, J =
6.6 Hz, 1H), 7.35 (d, J = 9 Hz, 2H), 8.44 (dd, J = 2.4 Hz, J = 6.6 Hz,
1H), 8.77 (dd, J = 2.4 Hz, J = 4.2 Hz, 1H), 9.25 (s, 1H), 10.25 (s, 1H,
NH); 13C-NMR (75 MHz, DMSO-d6): 40.7 (CH3), 55.1 (CH2), 107.7
(CH), 115.6 (CH), 121.2 (CH), 130.5 (C), 152.2(CH), 154.9 (C), 162.7
(C), 163.6 (CO), 164.9 (CH); HRMS (EI+) m/z calcd for C13H14N4O4S:
322.0736; found: 322.0737.
Statistics
Results are expressed as the mean l SEM. The data were statisti-
cally analyzed by the one-way ANOVA test and post-hoc Tuckey
test, with a significance level of * P a0.05 and ** P a0.01.
N1-(4-Hydroxyphenyl)-N2-(methylsulfonyl)-N2-pyrimidin-
2-ylglycinamide 7Bd
Yield: 20%; m.p.: 2978C; 1H-NMR (300 MHz, DMSO-d6): 3.37 (s, 3H),
4.89 (s, 2H), 6.69 (d, J = 8.7 Hz, 2H), 7.12 (t, J = 4.8 Hz, 1H), 7.34 (d, J
= 8.7 Hz, 2H), 8.61, (d, J = 4.8 Hz, 1H), 9.20 (br, 1H, OH), 10.03 (s,
1H, NH); 13C-NMR (75 MHz, DMSO-d6): 42.7 (CH3), 49.3 (CH2 ),
116.0 (CH), 116.8 (CH), 121.6 (CH), 131.2 (C), 154.2 (C), 159.0 (C),
163.2 (CH), 166.6 (CO).
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[(methylsulfonyl)imino]pyrimidin-1(2H)-yl]acetamide 6Be
1
Yield: 72%, decomp.; H-NMR (300 MHz, DMSO-d6): 3.15 (s, 3H),
[3] S. M. Sondhi, J. Shubhi, A. D. Dwivedi, R. Shukla, R. Raghu-
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5.14 (s, 2H), 7.13 (dd, J = 4.3 Hz, J = 6.5 Hz, 1H), 7.80 (m, 4H), 8.63
(dd, J = 2.4 Hz, J = 6.5 Hz, 1H), 8.99 (dd, J = 2.4 Hz, J = 4.3 Hz, 1H),
10.85 (s, 1H); 13C-NMR (75 MHz, DMSO-d6): 40.8 (CH3), 55.4 (CH2 ),
107.6 (CH), 115.6 (C), 121.3 (CH), 132.1 (CH), 139.0 (C), 152.1 (CH),
154.9 (C), 164.8 (CO), 165.12 (CH), HRMS (EI+) m/z calcd for
C13H13N4O3SBr: 383.9892; found: 383.9887.
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