Single-step syntheses of 2-amino-7-chlorothiazolo[5,4-d]pyrimidines: Intermediates for bivalent thiazolopyrimidines

Article abstract of DOI:10.1021/jo0517702

A single-step process for the preparation of 2-amino-7-chlorothiazolo[5,4- d]pyrimidines, 2, was achieved by the reaction of the commercially available 4,6-dichloro-5-aminopyrimidine 1 with isothiocyanates. This mild reaction accommodates a variety of fun

Full text of DOI:10.1021/jo0517702

tion,2c and others.2d-f However, among these various
cases, the 2,7-substitution pattern has been only mini-
mally explored.2c,d
Single-Step Syntheses of
2-Amino-7-chlorothiazolo[5,4-d]pyrimidines:
Intermediates for Bivalent
Thiazolopyrimidines
Jian Liu, Raymond J. Patch, Carsten Schubert, and
Mark R. Player*
Drug Discovery, Johnson & Johnson Pharmaceutical
Research and Development, L.L.C., 8 Clarke Drive,
Cranbury, New Jersey 08512
Common methods for assembling this bicyclic system
involve treatment of substituted pyrimidines with re-
agents such as phosgene,3a carbon disulfide,2e phosphorus
pentasulfide,4 or cyanogen bromide1a to form the fused
thiazole ring. Alternatively, the fused pyrimidine ring has
been formed from functionally advanced thiazoles by
treatment with reagents such as formamidine acetate,3b
carbon disulfide,5 formamide,6 and phosphorus pentox-
ide.7 However, both of these approaches suffer from the
requirements of using toxic reagents, harsh conditions,
and/or somewhat lengthy reaction sequences.3c-n
Herein, we report a convenient, single-step synthesis
of 2-amino-7-chlorothiazolo[5,4-d]pyrimidines directly
from commercially available 5-amino-4,6-dichloropyri-
midine and isothiocyanates under mild conditions. Fur-
thermore, the reactive 7-chloro substituent provides a
handle for additional functionalization to afford bivalent
2,7-disubstituted thiazolo[5,4-d]pyrimidines. In this Note,
we demonstrate the initial scope of this methodology by
the facile syntheses of a variety of 2,7-diaminothiazolo-
[5,4-d]pyrimidines (Figure 1).
During the course of a recent investigation with a
series of thioureas, we observed that treatment of 6-chloro-
N4-(3,4,5-trimethoxybenzyl)pyrimidine-4,5-diamine 4 (pre-
pared from 4,6-dichloro-5-aminopyrimidine 1 and 3,4,5-
trimethoxybenzylamine) with phenylisothiocyanate 5
under mild, basic conditions did not afford the desired
thiourea, but rather provided a product of further cy-
clization with concomitant loss of HCl. X-ray crystal-
lographic analysis provided unambiguous confirmation
mplayer@prdus.jnj.com
Received August 22, 2005
A single-step process for the preparation of 2-amino-7-
chlorothiazolo[5,4-d]pyrimidines, 2, was achieved by the
reaction of the commercially available 4,6-dichloro-5-ami-
nopyrimidine 1 with isothiocyanates. This mild reaction
accommodates a variety of functionalized isothiocyanates
and proceeds in good to excellent yields. The utility of such
intermediates is exemplified by subsequent reaction with
alkyl or arylamine nucleophiles to afford novel, differentially
functionalized 2,7-diaminothiazolo[5,4-d]pyrimidines, 3.
Thiazolopyrimidines have been widely recognized as
biologically useful systems due to their structural simi-
larities to purine bases. As such, thiazolopyrimidines
have been found to exhibit a range of biological activities,
particularly in the antiviral and immunology areas.1
Thiazolopyrimidines have also been utilized as templates
that have been additionally functionalized to achieve
selective receptor or enzyme interactions.2 In this capac-
ity, analogues have been identified with utilities as
chemokine receptor antagonists useful in treating neu-
rodegenerative disorders,2a as anti-angiogenic kinase
inhibitors,2b as inhibitors of MIF-induced T-cell prolifera-
(3) (a) Inuoe, S. Chem. Pharm. Bull. 1958, 6, 675. (b) Freeman, F.;
Kim, D. S. H. L. J. Org. Chem. 1991, 56, 4645. (c) Seela, F.; Ramzaeva,
N.; Rosemeyer, H. Sci. Synth. 2004, 16, 945 and references therein.
(d) Ulrich, H. Sci. Synth. 2002, 11, 835 and references therein. (e) Ram,
S.; Evans, W.; Wise, D. S., Jr.; Townsend, L. B.; McCall, J. W. J.
Heterocycl. Chem. 1989, 26, 1053. (f) Sen, A. K.; Chattopadhyay, G.
Indian J. Chem., Sect. B 1979, 18, 307. (g) Naito, T.; Inoue, S. Chem.
Pharm. Bull. 1958, 6, 338. (h) Takahashi, T.; Naito, T.; Inoue, S. Chem.
Pharm. Bull. 1958, 6, 334. (i) Sugiura, S.; Suzuki, E.; Naito, T.; Inoue,
S. Chem. Pharm. Bull. 1968, 16, 741. (j) Habib, N. S.; Rida, S. M.;
Badawey, E. A. M.; Fahmy, H. T. Y. Monatsh. Chem. 1996, 127, 1203.
(k) Habib, N. S.; Rida, S. M.; Badawey, E. A. M.; Fahmy, H. T. Y.
Monatsh. Chem. 1996, 127, 1209. (l) Lewis, A. F.; Revankar, G. R.;
Fennewald, S. M.; Huffman, J. H.; Rando, R. F. J. Heterocycl. Chem.
1995, 32, 547. (m) Badawey, E. S. A. M.; Rida, S. M.; Hazza, A. A.;
Fahmy, H. T. Y.; Gohar, Y. M. Eur. J. Med. Chem. 1993, 28, 91. (n)
Badawey, E. S. A. M.; Rida, S. M.; Hazza, A. A.; Fahmy, H. T. Y.;
Gohar, Y. M. Eur. J. Med. Chem. 1993, 28, 97.
(1) (a) Sircar, J. C.; Suto, M. J.; Scott, M. E.; Dong, M. K.; Gilbertsen,
R. B. J. Med. Chem. 1986, 29, 1804. (b) Revankar, G. R.; Ojwang, J.
O.; Mustain, S. D.; Rando, R. F.; De Clercq, E.; Huffman, J. H.; Drach,
J. C.; Sommadossi, J.-P.; Lewis, A. F. Antiviral Chem. Chemother.
1998, 9, 53. (c) Lewis, A. F.; Drach, J. C.; Fennewald, S. M.; Huffman,
J. H.; Ptak, R. G.; Sommadossi, J.-P.; Revankar, G. R.; Rando, R. F.
Antimicrob. Agents Chemother. 1994, 38, 2889. (d) Kini, G. D.;
Anderson, J. D.; Sanghvi, Y. S.; Lewis, A. F.; Smee, D. F.; Revankar,
G. R.; Robins, R. K.; Cottam, H. B. J. Med. Chem. 1991, 34, 3006. (e)
Nagahara, K.; Anderson, J. D.; Kini, G. D.; Dalley, N. K.; Larson, S.
B.; Smee, D. F.; Jin, A.; Sharma, B. S.; Jolley, W. B. J. Med. Chem.
1990, 33, 407. (f) Larson, S. B.; Anderson, J. D.; Cottam, H. B.; Robins,
R. K. Acta Crystallogr., Sect. C 1989, C45, 1073. (g) Larson, S. B.;
Anderson, J. D.; Cottam, H. B.; Robins, R. K. Acta Crystallogr., Sect.
C 1989, C45, 1822. (h) Robins, R. K.; Cottam, H. B. WO 8905649.
(2) (a) Nordvall, G.; Rein, T.; Sohn, D.; Zemribo, R. WO 2005033115.
(b) Luke, R. W. A.; Jones, C. D.; McCoull, W.; Hayter, B. R. WO
2004013141. (c) Sugihara, Y.; Horiguchi, T.; Maezaki, H.; Kimura, A.
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10.1021/jo0517702 CCC: $30.25 © 2005 American Chemical Society
Published on Web 10/26/2005
10194
J. Org. Chem. 2005, 70, 10194-10197

lamine (55%, entry 13) functioned similarly to DBU,
while TEA was quite unsatisfactory (10%, entry 14).
Among the inorganic bases we examined, Cs2CO3
provided the best result, affording an excellent yield of
thiazolopyrimidine (entry 17). However, the precise role
of Cs2CO3 in the present process is unclear. Thiourea
intermediates were not detected in any of these reactions,
indicating that their subsequent cyclizations are fast
regardless of the base used. The advantageous effects of
Cs2CO3 must be due to its influence on the initial
acylation step, possibly through the formation of a cesium
amide of 1. This aspect of the so-called “cesium effect”10
has been invoked by Salvatore et al. to provide mecha-
nistic rationale for the selective monoalkylation of pri-
mary amines in the presence of cesium hydroxide.11 To
our knowledge, such an effect upon arylamine acylations
has not been previously reported.
Having identified suitably optimized conditions for our
model reaction (entry 17), we next focused our investiga-
tion on determining the generality of this process with
respect to the nature of isothiocyanates that would
undergo this transformation. As indicated in Table 2, the
success of this reaction with arylisothiocyanates is ap-
parently largely independent of steric effects and, to a
certain extent, to electronic effects as well. Thus, even
the sterically encumbered 2,6-dimethylphenyl isothiocy-
anate underwent a smooth conversion to the correspond-
ing thiazolopyrimidine 18 (90%; entry 2). Electron-
donating groups such as p-Me and p-MeO are well
tolerated in this process (entries 3 and 4). However,
electron-withdrawing groups on the aryl isothiocyanate
are somewhat detrimental to this reaction, an effect that
is particularly pronounced in the case of p-nitrophenyl-
isothiocyanate (12 f 22, entry 6, 50%); less so with the
m-CF3 counterpart (11 f 21, entry 5, 82%). Finally,
heterocyclic arylisothiocyanates are also suitable for this
reaction, as exemplified by 3-pyridylisothiocyanate 13.
This electron-deficient isothiocyanate behaved similarly
to m-CF3-substituted phenylisothiocyanate 11, affording
thiazolopyrimidine 23 in a comparable yield (entry 7,
80%).
In contrast to the results obtained with aryl isothio-
cyanates, the course of reactions with aliphatic isothio-
cyanates proved to be susceptible to steric influences
(Table 3). Thus, whereas the reactions with tert-butyl and
isopropyl isothiocyanates afforded the corresponding
thiazolopyrimidines 24 and 25 in good yields (75 and
67%, respectively), less sterically demanding alkyl isothio-
cyanates over-reacted. Thus, with primary alkyl isothio-
cyanates 16 and 17, the initially formed 2-aminothiaz-
olopyrimidine adduct underwent a further smooth
acylation to form thiourea derivatives 26 and 27, respec-
tively (entries 3 and 4).
These latter results highlight the relative differences
in nucleophilicities between aminopyrimidine 1, primary
alkylaminothiazolopyrimidines A, secondary and tertiary
alkylaminothiazolopyrimidines B, and arylaminothiaz-
olopyrimidines C (Scheme 3). With primary alkylami-
FIGURE 1. Process for the preparation of 2,7-diaminothia-
zolo[5,4-d]pyrimidines.
of the thiazolopyrimidine structure 6 resulting from this
reaction.8 To our surprise, a literature survey revealed a
dearth of examples of thiazolo[5,4-d]pyrimidines with this
particular pattern of substitution. Thus, we initiated a
study to establish the scope and generality of this
sequence and to optimize reaction conditions for this type
of transformation.
As indicated in Scheme 1, the isolated yield of ben-
zothiazole 6 was modest (20% after 48 h), with mostly
unreacted diaminopyrimidine 4 remaining and no thio-
urea intermediate being detected. Reasoning that this
low conversion might be reflective of reduced nucleophi-
licity of the 5-amino group due to an intramolecular
hydrogen-bonding interaction between the adjacent amino
groups of 4, we reversed the reaction sequence (Scheme
2). In this case, treatment of dichloroaminopyrimidine 1
with phenylisothiocyanate under similar conditions led
to thiazolopyrimidine 7 with a 50% yield in 16 h.
Subsequent treatment of 7 with 3,4,5-trimethoxybenzy-
lamine under basic conditions afforded 6 in a 90% yield.
Encouraged by these results, we turned our attention
toward optimizing parameters affecting the formation of
7, namely solvent, temperature, and base (Table 1). In
screening a set of solvents, we observed a direct correla-
tion between polarity and yield (DMSO > DMF, MeCN
> acetone ≈ THF, DCM > toluene). Thus, the highest
yields of thiazolopyrimidine 7 were obtained in polar
aprotic solvents, whereas toluene proved to be the least
effective solvent for this transformation. While DMSO
provided the best yield for this reaction, we opted to
proceed with MeCN for purposes of practical handling.
In this solvent, a temperature increase from 25 to 50 °C
afforded a modest improvement in yield (60%, entry 8);
however, a further increase in temperature to 80 °C
proved to be detrimental to the process, leading to a
reduced yield of 7 among a more complex product mixture
(28%; entry 9).
Both the amount and choice of base were found to
influence the course of this reaction. Reducing the
amount of DBU from 2 equiv (entry 8) to one (entry 10)
resulted in a 33% decrease in thiazolopyrimidine product.
Without base, the reaction was quite slow; only a 5%
conversion was obtained (entry 11). This is in stark
contrast to the results obtained by Altland et al.9 with
3-amino-2-chloropyridine, wherein reaction with phenyl
isothiocyanate in refluxing ethanol afforded thiazolo[5,4-
b]pyridine in 67% yield without the requirement of
additional base. Given that pyridine proved unsuitable
for our reaction (3%, entry 12), this is suggestive of a
reduced nucleophilicity of aminopyrimidine 1 compared
with Altland’s aminopyridine system. Diisopropylethy-
(10) Flessner, T.; Doye, S. J. Prakt. Chem. 1999, 341, 186 and
references therein.
(8) Thermal ellipse rendering of compound 6 and corresponding
crystallographic information file are provided in the Supporting
(11) Salvatore, R. N.; Nagle, A. S.; Jung, K. W. J. Org. Chem. 2002,
67, 674.
Information.
(9) Altland, H. W.; Molander, G. A. J. Heterocycl. Chem. 1977, 14,
(12) All aryl and alkyl isothiocyanates were purchased from Sigma-
Aldrich and used directly.
129.
J. Org. Chem, Vol. 70, No. 24, 2005 10195

SCHEME 1. Formation of N2-Phenyl-N7-(3,4,5-trimethoxybenzyl)thiazolo[5,4-d]pyrimidine-2,7-diamine 6
SCHEME 2. Alternative Route to
N2-Phenyl-N7-(3,4,5-trimethoxybenzyl)thiazolo[5,4-d]pyrimidine-2,7-diamine 6
TABLE 1. Parameter Optimization for the Reaction of
4,6-Dichloro-5-aminopyrimidine 1 with Phenyl
Isothiocyanate
TABLE 3. Reaction of 4,6-Dichloro-5-aminopyrimidine 1
with Alkyl Isothiocyanates
entry isothiocyanate12
R1
R2
product (yield)
entry solvent temp (°C)
base
yield of 7 (%)
1
2
3
14
15
16
t-butyl-
2-propyl
Me-
H
H
24 (75%)
25 (67%)
26 (98%)a
1
DMSO
DMF
25
25
25
25
25
25
25
50
80
50
50
50
50
50
50
50
50
DBU (2 equiv)
DBU (2 equiv)
DBU (2 equiv)
DBU (2 equiv)
DBU (2 equiv)
DBU (2 equiv)
DBU (2 equiv)
DBU (2 equiv)
DBU (2 equiv)
DBU (1 equiv)
none
pyridine (2 equiv)
DIPEA (2 equiv)
TEA (2 equiv)
Na2CO3 (2 equiv)
K2CO3 (2 equiv)
Cs2CO3 (2 equiv)
60
50
50
44
40
40
10
60
28
40
5
2
3
MeCN
acetone
THF
4
5
4
17
PhCH2-
27 (94%)a
6
DCM
7
toluene
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
8
a Yield based on isothiocyanate.
9
10
11
12
13
14
15
16
17
3
The opposite is true with secondary and tertiary alky-
laminothiazolopyrimidines B, and with arylaminothiaz-
olopyrimidines C, whose amine nucleophilicities must be
less than that of 1 since no over-acylated adducts were
observed in their reactions (even in the presence of excess
isothiocyanate).
55
10
5
41
92
Finally, to demonstrate the synthetic utilities of these
intermediate 2-amino-7-chlorothiazolo[5,4-d]pyrimidines,
we have prepared a set of differentially substituted
thiazolo[5,4-d]pyrimidine-2,7-diamines (Table 4). Using
chlorothiazolo[5,4-d]pyrimidine 7 as our model system,
we found that amination could be effected quite readily
under thermal conditions without the assistance of metal
catalysis. Aliphatic amines reacted with 7 under basic
conditions, whereas aromatic amines required mildly
acidic conditions to undergo this transformation. Primary
and secondary aliphatic amines reacted smoothly to
afford the corresponding diamines in good to excellent
yields (entries 1-3). Even the weakly nucleophilic tert-
butylamine produced the corresponding product, 30,
albeit in modest yield (entry 4). The conditions employed
for aliphatic amine displacement were not suitable for
aromatic amines; the latter required a slight excess of
glacial acetic acid and microwave heating to enable this
displacement. Under such conditions, amination with
primary anilines occurred readily, affording the corre-
sponding 7-anilino products in good yields (entries 5-7).
However, both electronic and steric factors influenced this
TABLE 2. Reaction of 4,6-Dichloro-5-aminopyrimidine 1
with Aryl Isothiocyanates
entry
isothiocyanate12
R1
product (yield)
1
2
3
4
5
6
7
5
Ph-
7 (92%)
8
2,6-Me2Ph-
p-MePh-
18 (90%)
19 (93%)
20 (95%)
21 (82%)
22 (50%)
23 (80%)
9
10
11
12
13
p-MeOPh-
m-CF3Ph-
p-NO2Ph-
3-pyridyl-
nothiazolopyrimidines A, the exocyclic amino groups are
more nucleophilic than that of the aminopyrimidine
starting material itself; once formed, they out-compete
with 1 for the isothiocyanate electrophile that is present
in the reaction mixture, barring any steric encumbrance.
10196 J. Org. Chem., Vol. 70, No. 24, 2005

SCHEME 3. Relative Nucleophilicities toward Isothiocyanates
N2-Phenyl-N7-(3,4,5-trimethoxybenzyl)thiazolo[5,4-d]py-
rimidine-2,7-diamine (6). To a solution of 4 (162 mg, 0.5 mmol)
in DMF (2 mL) was added DBU (0.15 mL, 1 mmol) followed by
phenyl isothiocyanate 5 (0.06 mL, 0.5 mmol), and the resultant
mixture was stirred at room temperature for 48 h. After
concentration under reduced pressure, the residue was purified
by column chromatography (dichloromethane/MeOH, 19:1) to
give 6 as a white solid (42.4 mg, 20%): mp 110-111 °C; 1H NMR
(300 MHz, DMSO-d6): δ 10.62 (s, 1H), 8.21 (s, 1H), 7.99 (t, J )
5.4 Hz, 1H), 7.87 (d, J ) 7.8 Hz, 2H), 7.34 (dd, J ) 7.8, 7.5 Hz,
2H), 7.02 (t, J ) 7.5 Hz, 1H), 6.70 (s, 2H), 4.67 (d, J ) 5.4 Hz,
2H), 3.71 (s, 6H), 3.61 (s, 3H); 13C NMR (75 MHz, DMSO-d6): δ
157.8, 152.8 (2C), 152.7, 151.8, 140.4, 136.3, 135.8, 129.0 (2C),
128.8, 122.2, 117.8 (2C), 105.5, 104.7 (2C), 60.0, 56.5 (2C), 44.4;
HR-MS m/z (M + H+) calcd 424.1444, obsd 424.1444.
General Method for Preparation of 2-Amino-7-chlo-
rothiazolo[5,4-d]pyrimidines. To a solution of 4,6-dichloro-
5-aminopyrimidine 1 (164 mg, 1 mmol) in MeCN (4 mL) was
added Cs2CO3 (0.651 g, 2 mmol) followed by isothiocyanate (1
mmol). The mixture was stirred at 50 °C for 16 h, then cooled
to room temperature and concentrated under reduced pressure.
The resultant residue was purified by column chromatography
(hexanes/ethyl acetate, 4:1) to give the desired product.
Preparation of Thiazolo[5,4-d]pyrimidine-2,7-diamines:
Method A. Aliphatic Amines. A solution of (7-chlorothiazolo-
[5,4-d]pyrimidin-2-yl)phenylamine 7 (50 mg, 0.19 mmol), ali-
phatic amine (0.19 mmol), and TEA (0.026 mL, 0.19 mmol) in
THF (5 mL) was refluxed for 16 h. After being cooled to room
temperature and concentrated under reduced pressure, the
resulting residue was purified by column chromatography
(dichloromethane/MeOH, 9:1) to afford the corresponding sub-
stitution product. Using this protocol, we obtained N2-phenyl-
N7-(3,4,5-trimethoxybenzyl)thiazolo[5,4-d]pyrimidine-2,7-di-
amine (6) as a white solid (72 mg, 90%).
Preparation of Thiazolo[5,4-d]pyrimidine-2,7-diamines:
Method B. Aromatic Amines. A solution of (7-chlorothiazolo-
[5,4-d]pyrimidin-2-yl)phenylamine 7 (50 mg, 0.19 mmol), the
aromatic amine (0.28 mmol), glacial acetic acid (0.016 mL, 0.28
mmol), and dioxane (2.5 mL) in a sealed tube was heated to 150
°C in microwave reactor (Smith Synthesizer, Personal Chemis-
try) for 40 min. After being cooled to room temperature and
concentrated under reduced pressure, the resulting residue was
purified by column chromatography (dichloromethane/MeOH,
19:1) to afford the corresponding substitution product.
TABLE 4. Amination of
(7-Chlorothiazolo[5,4-d]pyrimidin-2-yl)phenylamine 7
entry
R1
R2
producta,b
1
2
3
4
5
6
7
8
9
3,4,5-(MeO)3PhCH2-
H
6 (90%)
-(CH2)2-NMe-(CH2)2-
28 (85%)
29 (90%)
30 (20%)c
31 (93%)
32 (86%)
33 (90%)
34 (22%)d
35 (60%)
Me-(CH2)3-
t-butyl-
Ph-
p-MeOPh-
m-ClPh-
p-NO2Ph-
Ph-
H
H
H
H
H
H
Me-
a Reaction conditions for alkylamines: 1.0 equiv of amine; 1.0
equiv of TEA; refluxed in 5.0 mL of THF for 16 h. b Reaction
conditions for arylamines: 1.5 equiv of amine; 1.5 equiv of acetic
acid; heated in 2.5 mL of dioxane in a microwave reactor at 150
°C for 40 min. c Reaction time was 72 h. d Reaction was carried
out at 200 °C for 8 h.
substitution reaction as evidenced by the moderate yields
of 34 and 35, respectively (entries 8 and 9).
In summary, we have established a convenient method
for the preparation of 2-amino-7-chlorothiazolo[5,4-d]-
pyrimidines, which are versatile synthetic intermediates
for subsequent derivatization upon treatment with reac-
tive nucleophiles. In this present work, we have prepared
a set of novel, bivalent thiazolo[5,4-d]pyrimidine-2,7-
diamines, which are being investigated for biological
utilities.
Experimental Section
6-Chloro-N4-(3,4,5-trimethoxybenzyl)pyrimidine-4,5-di-
amine (4). To a solution of 4,6-dichloro-5-aminopyrimidine 1
(2.0 g, 12.2 mmol) in n-BuOH (25 mL) were added TEA (2.04
mL, 14.6 mmol) and 3,4,5-trimethoxybenzylamine (2.19 mL, 12.8
mmol). The reaction mixture was heated to 80 °C and stirred
for 16 h, then cooled to room temperature and concentrated
under reduced pressure. The residue thus obtained was purified
by column chromatography (hexanes/ethyl acetate, 1:1) to afford
4 as an off-white solid (3.17 g, 80%). 1H NMR (300 MHz, DMSO-
d6): δ 7.76 (s, 1H), 7.22 (t, J ) 5.4 Hz, 1H), 6.67 (s, 2H), 5.11 (s,
2H), 4.54 (d, J ) 5.4 Hz, 2H), 3.74 (s, 6H), 3.63 (s, 3H); 13C NMR
(75 MHz, DMSO-d6): δ 152.8, 151.8, 145.6, 137.0, 136.5, 134.9
(2C), 123.6, 105.0 (2C), 60.0, 55.8 (2C), 44.7; HR-MS m/z (M +
H+) calcd 325.1068, obsd 325.1078.
Acknowledgment. We thank Mr. William Jones for
carrying out HRMS analyses.
Supporting Information Available: Analytical data and
1H NMR spectra for all product compounds (Tables 2-4) and
a thermal ellipse rendering and corresponding crystallographic
information file for compound 6. This material is available free
of charge via the Internet at http://pubs.acs.org.
JO0517702
J. Org. Chem, Vol. 70, No. 24, 2005 10197