Prompt lithiation of 1-dimethylsulfamoylthymine used for the synthesis of 1-allyloxymethyl-6-(α,2,6-trifluorobenzyl)thymine

Article abstract of DOI:10.1055/S-0029-1216978

The 6-position of the uracil ring was activated for a lithiation reaction by condensing thymine with dimethylsulfamoyl chloride. X-ray crystallography was used to confirm the structure of the intermediate product 1- dimethylsulfamoylthymine, which was lit

Full text of DOI:10.1055/S-0029-1216978

PAPER
3589
Prompt Lithiation of 1-Dimethylsulfamoylthymine Used for the Synthesis
of 1-Allyloxymethyl-6-(a,2,6-trifluorobenzyl)thymine
S
a
ynthesis of 1-Ally
a
loxymethy
s
l-6-(
a
,2,6
s
-trifluorob
e
enzyl)thym
r
ine M. Loksha,a Erik B. Pedersen,*a Andrew D. Bond,b Paolo La Colla,c Barbara Secci,c Roberta Loddoc
Nucleic Acid Centre, Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
Fax +4566158780; E-mail: ebp@ifk.sdu.dk
b
c
Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
Dipartimento di Scienze e Tecnologie Biomediche, Sezione di Microbiologia e Virologia Generale e Biotecnologie Microbiche,
Università di Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy
Received 16 March 2009; revised 19 June 2009
derivatives that should be suitable starting materials. Di-
methylsulfamoyl has been used for activating heterocy-
clic rings towards lithiation reactions,12–17 but it has not so
far been used to activate a uracil ring towards lithiation. In
Abstract: The 6-position of the uracil ring was activated for a lithi-
ation reaction by condensing thymine with dimethylsulfamoyl chlo-
ride. X-ray crystallography was used to confirm the structure of the
intermediate product 1-dimethylsulfamoylthymine, which was
lithiated and subsequently treated with 2,6-difluorobenzaldehyde. this paper, the inexpensive and readily available dimeth-
The dimethylsulfamoyl group was removed by treatment with aq
ylsulfamoyl group has been found to be useful for activat-
HCl and the alcohol was fluorinated with DAST. The fluoro-deriv-
ing the 6-position of the thymine ring towards lithiation.
ative was silylated and alkylated at the N1-position with bis(allyl-
In the search for a new synthesis of S-DABOs, an attempt
was made to prepare an activated pyrimidine ring for lithi-
ation reactions by N1-substitution. 5-Methyl-2-(methyl-
thio)pyrimidin-4(3H)-one was treated with dimethyl-
sulfamoyl chloride in anhydrous acetonitrile using 1,8-di-
azabicyclo[5.4.0]-undec-7-ene (DBU), however, the iso-
lated product from the reaction was found to be 5-methyl-
2-(methylthio)pyrimidin-4-yl dimethylsulfamate (2),
formed from O-coupling, and not the desired compound 3
(Scheme 1). The structure of compound 2 was confirmed
by X-ray crystallography (Figure 1) and also by chemical
reactions. Treatment of 2 with 40% aqueous dimethyl-
amine at room temperature afforded N,N-5-trimethyl-2-
(methylthio)pyrimidin-4-amine (4) in 96% yield. Reflux-
ing compound 2 with 2,4,6-trimethylaniline in ethanol, in
the presence of acetic acid, gave N-mesityl-5-methyl-2-
(methylthio)pyrimidin-4-amine (5). The dimethylsulfa-
mate group at the 4-position of the pyrimidine ring did not
activate the 6-position of compound 2 for lithiation, in-
deed, when lithiation was attempted on 2, followed by
treatment with 2,6-difluorobenzaldehyde, only the start-
ing material 2 was recovered.
oxy)methane to give 1-allyloxymethyl-6-[(2,6-difluorophenyl)fluo-
romethyl]-5-methylpyrimidine-2,4(1H,3H)-dione, which showed
moderate activity against HIV-1. An attempt was also made to acti-
vate 5-methyl-2-(methylthio)pyrimidin-4(3H)-one with dimethyl-
sulfamoyl chloride for a lithiation reaction. However, X-ray
crystallography and subsequent reactions showed that the sulfa-
moylation had taken place on the oxygen at the 4-position.
Key words: antiviral agents, heterocycles, HIV, medicinal chemis-
try, sulfonamides
The non-nucleoside 6-benzyl-1-ethoxymethyl-5-isopro-
pyluracil (MKC-442) and its 2-alkylthio-3,4-dihydro-4-
oxopyrimidine analogues (S-DABO) have shown high
activity against HIV-1 wild type in micromolar scale.1–3
Alkyloxymethyl protecting groups have been used by
Tanaka et al.3 to activate the 6-position in uracils for lithi-
ation and subsequent reaction with an aldehyde in order to
prepare 6-arylmethyl-1-alkyloxymethyl derivatives as
analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenyl-
thio)thymine (HEPT).4,5 The alkyloxymethyl type of pro-
tecting group has also been used by others,6,7 and it is
difficult to find other types of protecting groups in the lit-
erature for deprotonation of hydrogen in the 6-position of
uracils. Lithiation has been achieved by hydrogen abstrac-
tion from the 6-position in a 2,4-dimethoxypyrimidine de-
rivative, which can also be considered to be a protected
uracil derivative. Several examples are known for the syn-
thesis of 6-substituted uracil derivatives using the corre-
sponding halogen-substituted pyrimidines or uracils in a
organometallic reaction.8–11 For the preparation of new
types of fluoro derivatives of MKC-442, we now focus on
the dimethylsulfamoyl group as a potential protecting
group in lithiation reactions for the preparation of uracil
Figure 1 X-ray crystal structure of compound 2 (displacement el-
lipsoids shown at 50% probability for non-H atoms)
SYNTHESIS 2009, No. 21, pp 3589–3592
Advanced online publication: 28.08.2009
x
x.
x
x
.
2
0
0
9
DOI: 10.1055/s-0029-1216978; Art ID: T05909SS
© Georg Thieme Verlag Stuttgart · New York

3590
Y. M. Loksha et al.
PAPER
ment with bis(allyloxy)methane,18 in the presence of tri-
methylsilyl trifluoromethanesulfonate (TMS-triflate) as a
Lewis acid catalyst at –50 °C, to give the expected prod-
OSO2N(Me)2
N
S
N
uct
1-(allyloxymethyl)-6-[(2,6-difluorophenyl)fluoro-
O
N
Me
methyl]-5-methylpyrimidine-2,4(1H,3H)-dione
Scheme 2).
(10;
2
HN
(Me)2NSO2Cl
DBU, MeCN
O
S
i) n-BuLi, –78 °C
N
Me
1
F
O
N
O
O
S
N
ii)
Me
SO2N(Me)2
HN
HN
(Me)2NSO2Cl
DBU, MeCN
F
3
iii) 4 M HCl, r.t.
O
O
N
H
SO2N(Me)2
NH
6
7
N
O
O
NH2
N
40% aq (Me)2NH
r.t.
N
2
EtOH,
AcOH, reflux
HN
F
HN
F
DAST, CH2Cl2
–5 °C
S
N
S
N
Me
Me
5
4
O
N
H
O
N
H
OH
F
F
F
Scheme 1
8
9
O
In contrast, treatment of thymine with dimethylsulfamoyl
chloride in anhydrous acetonitrile in the presence of DBU,
gave the desired compound N,N-5-trimethyl-2,4-dioxo-
3,4-dihydropyrimidine-1(2H)-sulfonamide (7) as the sole
product (Scheme 2). In addition to NMR, MS and mi-
croanalysis, X-ray crystallography confirmed that N-cou-
pling had occurred (Figure 2).
HN
F
i) BSA, MeCN, r.t.
ii) TMSOTf, –50 °C
iii) (CH=CH-CH2O)2CH2
O
N
F
F
O
10
Scheme 2
Compound 10 was evaluated in cell-based assays against
HIV-1 wild-type and its clinically relevant NNRTI resis-
tant mutants. It showed moderate activity against HIV-1
wild-type (EC50 = 3 mM; CC50 = >100 mM; Selectivity In-
dex [SI] = >33) compared to MKC-442 (EC50 = 0.03 mM;
CC50 = 100 mM; Selectivity Index [SI] = 3333). Cytotox-
icity of compounds was evaluated in parallel with the an-
tiviral activity.
X-ray diffraction data were collected using a Bruker Nonius X8-
ApexII instrument with MoKa radiation. NMR spectra were record-
ed on a Varian Gemini 2000 spectrometer at 300 MHz for 1H and
75 MHz for 13C with TMS as an internal standard. EI mass spectra
were recorded on a Finnigan MAT SSQ 710. MALDI spectra were
recorded on a 4.7 T Ultima Fourier transform mass spectrometer
(IonSpec, Irvine, CA). Melting points were determined in a Büchi
melting point apparatus. The silica gel (0.040–0.063 mm) used for
column chromatography was purchased from Merck. Microanaly-
ses were carried out at Chemical Laboratory II at University of
Copenhagen, Denmark.
Figure 2 X-ray crystal structure of compound 7 (displacement el-
lipsoids shown at 50% probability for non-H atoms)
Compound 7 was lithiated using n-butyllithium at –78 °C
in THF, followed by treatment with 2,6-difluorobenzalde-
hyde at –78 °C. The reaction was stirred with 4 M hydro-
chloric acid at room temperature in order to remove the
dimethylsulfamoyl group, giving 6-[(2,6-difluorophe-
nyl)hydroxymethyl]-5-methylpyrimidine-2,4(1H,3H)-di-
Compounds 2 and 7; General Procedure
A mixture of DBU (5.5 mL, 36 mmol) and 5-methyl-2-(methyl-
one
(8).
6-[(2,6-Difluorophenyl)fluoromethyl]-5- thio)pyrimidin-4(3H)-one or thymine (0.03 mol) in anhyd MeCN
(50 mL) was stirred for 15 min. Dimethylsulfamoyl chloride (3.3
methylpyrimidine-2,4(1H,3H)-dione (9) was obtained by
fluorination of compound 8 using diethylaminosulfur tri-
fluoride (DAST) in anhydrous methylene chloride
(Scheme 2).
mL, 0.3 mol) was added and the mixture was stirred overnight then
neutralized by dropwise addition of 4 M HCl. The solvent was re-
moved under reduced pressure. H2O (30 mL) and CH2Cl2 (30 mL)
were added, the mixture was stirred for 10 min and the two layers
were separated. The H2O layer was extracted with CH2Cl2 (2 × 20
mL) and the combined organic phases were dried (MgSO4) and
evaporated under reduced pressure. The residual material was puri-
One example of an Emivirine (MKC-442) analogue was
synthesized by silylation of compound 9 using N,O-
bis(trimethylsilyl)acetamide (BSA) followed by treat-
Synthesis 2009, No. 21, 3589–3592 © Thieme Stuttgart · New York

PAPER
Synthesis of 1-Allyloxymethyl-6-(a,2,6-trifluorobenzyl)thymine
3591
fied by silica gel column chromatography (CH2Cl2–EtOAc, 10:1) to
6-[(2,6-Difluorophenyl)hydroxymethyl]-5-methylpyrimidine-
afford the products 2 and 7.
2,4(1H,3H)-dione (8)
Under a nitrogen atmosphere, n-BuLi (2 M in THF, 5 mL, 11 mmol)
was added dropwise at –78 °C to a solution of compound 7 (1.17 g,
5 mmol) in anhyd THF (15 mL) and the reaction mixture was stirred
at –78 °C for 1 h. 2,6-Difluorobenzaldehyde (0.8 g, 5.5 mmol) in
anhyd THF (2 mL) was added dropwise and the mixture was stirred
at –78 °C for 1 h, then left to warm gradually to r.t. with stirring
overnight. The reaction was quenched with H2O (1 mL) followed by
addition of 4 M HCl (15 mL) and stirring was continued for 1 h. The
resulting solid product was filtered off, washed with H2O, and dried
to afford compound 8 as a pure solid.
5-Methyl-2-(methylthio)pyrimidin-4-yldimethylsulfamate (2)
Yield: 5.28 g (67%); mp 50–52 °C.
1H NMR (DMSO-d6): d = 2.16 (s, 3 H, CH3), 2.52 (s, 3 H, CH3S),
3.01 [s, 6 H, (CH3)2N], 8.60 (s, 1 H, H-6).
13C NMR (DMSO-d6): d = 11.5 (CH3), 13.6 (CH3S), 38.3
[(CH3)2N], 115.4 (C5), 160.9 (C6), 161.8 (C2), 168.7 (C4).
MS (EI): m/z (%) = 263 (30) [M+], 156 (100).
Anal. Calcd for C8H13N3O3S2: C, 36.49; H, 4.98; N, 15.96. Found:
C, 36.17; H, 5.34; N, 16.23.
Yield: 0.95 g (71%); mp 210–212 °C.
1H NMR (DMSO-d6): d = 1.46 (s, 3 H, CH3), 5.95 (s, 1 H, CH-OH),
7.16 (t, J = 8.4 Hz, 2 H, ArH), 7.44–7.54 (m, 1 H, ArH), 11.09 (br
s, 1 H, NH).
13C NMR (DMSO-d6): d = 8.1 (CH3), 59.5 (t, J = 3.2 Hz, CH-OH),
102.1 (C5), 112.1 (dd, J = 7.3, 17.6 Hz, Ar), 116.1 (t, J = 17.7 Hz,
Ar), 131.2 (t, J = 10.5 Hz, Ar), 149.9 (C4), 150.0 (C2), 160.3 (dd,
J = 7.8, 249.0 Hz, Ar), 164.6 (C4).
N,N-5-Trimethyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-sul-
fonamide (7)
Yield: 2.5 g (36%); mp 190–192 °C.
1H NMR (DMSO-d6): d = 1.81 (s, 3 H, CH3), 2.94 [s, 6 H, (CH3)2N],
7.78 (s, 1 H, H-6), 11.72 (s, 1 H, NH).
13C NMR (DMSO-d6): d = 12.0 (CH3), 38.1 [(CH3)2N], 110.3 (C5),
135.7 (C6), 148.3 (C2), 163.6 (C4).
MS (EI): m/z (%) = 233 (20) [M+].
MS (EI): m/z (%) = 268 (100) [M+].
Anal. Calcd for C12H10F2N2O3·0.25H2O: C, 52.85; H, 3.88; N,
10.27. Found: C, 52.51; H, 3.19; N, 10.01.
Anal. Calcd for C7H11N3O4S: C, 36.05; H, 4.75; N, 18.02. Found:
C, 36.36; H, 4.88; N, 17.77.
6-[(2,6-Difluorophenyl)fluoromethyl]-5-methylpyrimidine-
2,4(1H,3H)-dione (9)
N,N-5-Trimethyl-2-(methylthio)pyrimidin-4-amine (4)
Compound 2 (0.53 g, 2 mmol) was stirred in a mixture of 40% aq
Me2NH (15 mL) and EtOH (5 mL) for 2 h at r.t. The reaction mix-
ture was concentrated to 5 mL under reduced pressure, H2O (10 mL)
was added, and the solid product formed was filtered off and dried
to afford compound 4 as the sole product.
To a stirred solution of compound 8 (0.4 g, 1.5 mmol) in anhyd
CH2Cl2 (2 mL), was added DAST (0.3 mL, 2.3 mmol) in CH2Cl2 (1
mL) dropwise at –5 °C. The mixture was allowed to reach r.t. and
stirred for 3 h then 5% aq NaHCO3 (0.2 mL) was added, followed
by addition of H2O (5 mL) and CH2Cl2 (10 ml). The two layers were
separated and the organic layer was dried (Na2SO4) and evaporated
under reduced pressure. The residual oily product was purified by
silica gel column chromatography (Et2O) to afford compound 9.
Yield: 0.35 g (96%); mp 54–56 °C.
1H NMR (DMSO-d6): d = 2.20 (s, 3 H, CH3), 2.42 (s, 3 H, CH3S),
3.06 [s, 6 H, (CH3)2N], 7.83 (s, 1 H, H6).
13C NMR (DMSO-d6): d = 13.2 (CH3), 17.4 (CH3S), 39.5
[(CH3)2N], 110.3 (C5), 157.0 (C6), 162.8 (C2), 166.5 (C4).
MS (EI): m/z (%) = 183 (100) [M+].
Yield: 0.3 g (75%); mp 224–226 °C.
1H NMR (DMSO-d6): d = 1.50 (s, 3 H, CH3), 6.97 (d, JH,F = 43.5
Hz, 1 H, CH-F), 7.27 (t, J = 8.7 Hz, 2 H, ArH), 7.62–7.72 (m, 1 H,
ArH), 10.98 (br s, 1 H, NH).
HRMS (MALDI): m/z [MH+] calcd for C8H14N3S: 184.0903; found:
184.0894.
13C NMR (DMSO-d6): d = 8.2 (CH3), 79.5 (d, J = 174.8 Hz, CH-
F), 103.1 (C5), 112.5 (dd, J = 5.9, 16.3 Hz, Ar), 116.8 (t, J = 17.4
Hz, Ar) 133.7 (t, J = 10.8 Hz, Ar), 145.8 (d, J = 21.7 Hz, C6), 150.4
(C2), 160.5 (d, J = 7.8, 249.0 Hz, Ar), 164.2 (C4).
Anal. Calcd for C8H13N3S: C, 52.43; H, 7.15; N, 22.90. Found: C,
52.64; H, 7.32; N, 22.94.
HRMS-MALDI: m/z [MH+] calcd for C12H10F3N2O2: 271.0689;
N-Mesityl-5-methyl-2-(methylthio)pyrimidin-4-amine (5)
Compound 2 (0.53 g, 2 mmol) and 2,4,6-trimethylaniline (0.27 mL,
2.2 mmol) were refluxed in a mixture of EtOH (15 mL) and AcOH
(1 mL) for 12 h. The solvents were evaporated under reduced pres-
sure and the residual material was purified by chromatography on a
silica gel column (PE–Et2O, 3:1) to furnish compound 5.
found: 271.0693.
1-(Allyloxymethyl)-6-[(2,6-difluorophenyl)fluoromethyl]-5-
methylpyrimidine-2,4(1H,3H)-dione (10)
BSA (0.3 mL, 1.2 mmol) was added to a stirred solution of com-
pound 9 (95 mg, 0.35 mmol) in anhyd CH2Cl2 (10 mL) under a ni-
trogen atmosphere and, after 15 min, the mixture was cooled to
–50 °C. TMS-triflate (0.06 mL, 0.35 mmol) was added, followed by
bis(allyloxy)ethane (0.09 g, 0.7 mmol) and the mixture was left to
reach r.t. with stirring overnight. The reaction was quenched by ad-
dition of sat. aq Na2CO3 (0.5 mL), then H2O (10 mL) was added and
the two layers were separated. The organic phase was dried
(MgSO4) and evaporated under reduced pressure. The residual ma-
terial was purified by a silica gel column chromatography (CH2Cl2–
EtOAc, 1:1) to give compound 10.
Yield: 0.22 g (40%); mp 152–154 °C.
1H NMR (CDCl3): d = 2.10 (s, 3 H, CH3-C5), 2.14 [s, 6 H,
(CH3)2Ar], 2.23 (s, 3 H, CH3Ar), 2.30 (s, 3 H, CH3-S), 5.81 (s, 1 H,
NH), 6.90 (s, 2 H, ArH), 7.89 (s, 1 H, H-6).
13C NMR (CDCl3): d = 13.4 (CH3-C5), 13.7 (CH3-S), 18.5
[(CH3)2Ar], 20.9 (CH3Ar), 108.2 (C5), 128.6, 132.6, 135.6, 136.4
(Ar), 154.8 (C6), 159.6 (C2), 169.3 (C4).
HRMS (MALDI): m/z [M+ + H] calcd for C15H20N3S: 274.1372;
found: 274.1376.
Yield: 90 mg (76%); mp 96–98 °C.
1H NMR (CDCl3): d = 1.72 (s, 3 H, CH3), 4.18 (dt, JH,F = 5.4, 1.5
Hz, 2 H, OCH2-CH), 5.17 (dd, J = 10.2, 1.5 Hz, 1 H, HCH=CH),
5.34 (dd, J = 10.2, 1.5 Hz, 1 H, HCH=CH), 5.44 (s, 2 H, NCH2O),
5.85–5.98 (m, 1 H, CH2=CH), 6.73 (d, JH,F = 44.1 Hz, 1 H, CH-F),
Anal. Calcd for C15H19N3S: C, 65.90; H, 7.00; N, 15.37. Found: C,
65.94; H, 7.20; N, 15.43.
Synthesis 2009, No. 21, 3589–3592 © Thieme Stuttgart · New York

3592
Y. M. Loksha et al.
PAPER
7.01 (t, J = 9.0 Hz, 2 H, ArH), 7.26–7.52 (m, 1 H, ArH), 8.42 (br s,
1 H, NH).
(2) Yuasa, S.; Sadakata, Y.; Takashima, H.; Sekiya, K.; Inouye,
N.; Ubasawa, M.; Baba, M. Mol. Pharmacol. 1993, 44, 895.
(3) Mai, A.; Artico, M.; Sbardella, G.; Massa, S.; Loi, A. G.;
Tramontano, E.; Scano, P.; La Colla, P. J. Med. Chem. 1995,
38, 2860.
(4) Baba, M.; Tanaka, H.; De Clercq, E.; Pauwels, R.; Balzarini,
J.; Schols, D.; Nakashima, H.; Perno, C.-F.; Walker, R. T.;
Miyasaka, T. Biochem. Biophys. Res. Commun. 1989, 165,
1375.
(5) Miyasaka, T.; Tanaka, H.; Baba, M.; Hayakawa, H.; Walker,
R. T.; Balzarini, J.; De Clercq, E. J. Med. Chem. 1989, 32,
2507.
(6) Petersen, L.; Jessen, C. H.; Pedersen, E. B.; Nielsen, C. Org.
Biomol. Chem. 2003, 1, 3541.
13C NMR (CDCl3): d = 9.2 (CH3), 70.1 (OCH2CH), 71.3 (NCH2O),
79.5 (d, JC,F = 179 Hz, CH-F), 105.2 (C5), 112.4 (dd, J = 2.8, 20.1
Hz, Ar), 116.5 (t, J = 17.6 Hz, Ar), 117.3 (CH2=CH), 133.2 (t,
J = 11.0 Hz, Ar), 142.9 (d, J = 22.4 Hz, C6), 150.4 (C2), 146.7
(CH2=CH), 161.0 (dd, J = 7.8, 249.0 Hz, Ar), 163.7 (C4).
HRMS-MALDI: m/z [M+ + Na] calcd for C16H15F3NaN2O3:
363.0927; found: 363.0924.
X-ray crystal data
Crystal data for 2: empirical formula C8H13N3O3S2; formula weight
263.33; triclinic; space group P–1; a = 6.8695(2) Å, b = 7.6535(3)
Å,
c = 13.0800(4)
Å,
a = 93.239(1)°,
b = 103.740(1)°,
(7) Meng, G.; Kuang, Y.-Y.; Ji, L.; Chen, F.-E. Synth. Commun.
2005, 35, 1095.
(8) Kumarasinghe, E. S.; Peterson, M. A.; Robins, M. J.
Tetrahedron Lett. 2000, 41, 8741.
g = 116.422(1)°; V = 587.74(3) Å3; Z = 2; Dcalcd = 1.488 Mg m–3;
l = 0.7107 Å; absorption coefficient = 0.499 mm–1; F(000) = 276;
T = 180(2) K; crystal size = 0.40 × 0.25 × 0.15 mm. CCDC 716979
contains the supplementary crystallographic data for this com-
pound.
(9) Boudet, N.; Knochel, P. Org. Lett. 2006, 8, 3737.
(10) Kopp, F.; Knochel, P. Org. Lett. 2007, 9, 1639.
(11) El-Brollosy, N. R.; Sørensen, E. R.; Pedersen, E. B.; Sanna,
G.; La Colla, P.; Loddo, R. Arch. Pharm. 2008, 341, 9.
(12) Loksha, Y. M.; El-Barbary, A. A.; El-Badawi, M. A.;
Nielsen, C.; Pedersen, E. B. Synthesis 2004, 116.
(13) Turner, R. M.; Lindell, S. D.; Ley, S. V. J. Org. Chem. 1991,
56, 5739.
(14) Winter, J.; Retey, J. Synthesis 1994, 245.
(15) Sahli, S.; Stump, B.; Welti, T.; Schweizer, W. B.; Diederich,
F.; Blum-Kaelin, D.; Aebi, J. D.; Boehm, H.-J. Helv. Chim.
Acta 2005, 88, 707.
Crystal data for 7: empirical formula C7H11N3O4S; formula weight
233.25; monoclinic; space group P21/n; a = 6.3567(3) Å,
b = 9.0104(5) Å, c = 17.6044(9) Å, a = 90°, b = 92.413(2)°,
g = 90°; V = 1007.42(9) Å3; Z = 4; Dcalcd = 1.538 Mg m–3;
l = 0.7107 Å; absorption coefficient = 0.321 mm–1; F(000) = 488;
T = 180(2) K; crystal size = 0.25 × 0.15 × 0.15 mm. CCDC 716980
contains the supplementary crystallographic data for this com-
pound.
Acknowledgment
(16) Madsen, C.; Jensen, A. A.; Liljefors, T.; Kristiansen, U.;
Nielsen, B.; Hansen, C. P.; Larsen, M.; Ebert, B.; Bang-
Andersen, B.; Krogsgaard-Larsen, P.; Froelund, B. J. Med.
Chem. 2007, 50, 4147.
This work received funding from the European Community’s Sixth
Framework Programme under contract number LSHP-CT-2004-
503162 (Selection and development of microbicides for mucosal
use to prevent sexual HIV transmission/acquisition).19
(17) Guianvarc’h, D.; Fourrey, J.-L.; Maurisse, R.; Sun, J.-S.;
Benhida, R. Org. Lett. 2002, 4, 4209.
(18) El-Brollosy, N. R.; Jørgensen, P. T.; Dahan, B.; Boel, A. M.;
Pedersen, E. B.; Nielsen, C. J. Med. Chem. 2002, 45, 5721.
(19) The information in this document is provided as is and no
guarantee or warranty is given that the information is fit for
any particular purpose. The user thereof uses the information
as its sole risk and liability.
References
(1) Baba, M.; Shigeta, S.; Yuasa, S.; Takashima, H.; Sekiya, K.;
Ubasawa, M.; Tanaka, H.; Miyasaka, T.; Walker, R. T.;
De Clercq, E. Antimicrob. Agents Chemother. 1994, 38, 688.
Synthesis 2009, No. 21, 3589–3592 © Thieme Stuttgart · New York