Synthesis of 2-(2-imino-2,3-dihydropyrido[3,2-e]-1,3-thiazin-(Z)-4-ylidene) acetamide derivatives

Article abstract of DOI:10.1055/s-2008-1067015

A facile two-step preparation of the title pyridothiazine derivatives starting from commercially available 2-chloro-6-methylpyridine-3-carbonitrile is described. The reaction of this nitrile with magnesium enolates of tertiary acetamides affords (Z)-3-ami-no-3-(2-chloro-6-methylpyridin-3-yl)propenamide derivatives, which in turn are allowed to react with isothiocyanates in the presence of sodium hydride to give the desired products in satisfactory yields.

Full text of DOI:10.1055/s-2008-1067015

PAPER
1703
Synthesis of 2-(2-Imino-2,3-dihydropyrido[3,2-e]-1,3-thiazin-
(Z)-4-ylidene)acetamide Derivatives
S
ynthesis of Pyrid
a
othizine
D
e
z
rivatives uhiro Kobayashi,* Daisuke Iitsuka, Hisatoshi Konishi
Department of Materials Science, Faculty of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
Fax +81(857)315263; E-mail: kkoba@chem.tottori-u.ac.jp
Received 11 January 2008; revised 18 February 2008
NH2
Abstract: A facile two-step preparation of the title pyridothiazine
CONR1
2
NaH (2 equiv), R2NCS, DMF, 0 °C
derivatives starting from commercially available 2-chloro-6-meth-
ylpyridine-3-carbonitrile is described. The reaction of this nitrile
with magnesium enolates of tertiary acetamides affords (Z)-3-ami-
Me
N
Cl
no-3-(2-chloro-6-methylpyridin-3-yl)propenamide
derivatives,
1a NR12 = NMe2
1b NR12 = morpholin-4-yl
1c NR12 = pyrrolidin-1-yl
which in turn are allowed to react with isothiocyanates in the pres-
ence of sodium hydride to give the desired products in satisfactory
yields.
CONR1
2
Key words: amides, cyclizations, heterocycles, imines, pyridines
H3O+
N
S
NR2
Me
N
Cl
We recently reported a convenient method to prepare
(Z)-2-(2-oxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-
ylidene)acetamide derivatives.1 This synthesis was based
on the reaction of (Z)-3-amino-3-(2-chloro-6-methylpyri-
din-3-yl)propenamide derivatives 1 with aryl isocyanates
in the presence of sodium hydride. Compounds 1 were
easily prepared by the treatment of commercially avail-
able 2-chloro-6-methylpyridine-3-carbonitrile with mag-
nesium enolates of tertiary acetamides.
2
CONR1
NH
CONR1
2
2
not
NH
S
Me
N
S
NR2
Me
N
N
R2
3
4
In continuation of our study, we became interested in ex-
amining the reaction of the enamino amides 1 with
isothiocyanates. We found that the reaction gave 2-(2-imi-
no-2,3-dihydropyrido[3,2-e]-1,3-thiazin-(Z)-4-ylidene)acet-
amide derivatives 3, as shown in Scheme 1. In this paper,
we report a facile method for the preparation of these py-
ridothiazine derivatives.
Scheme 1
Conversion of the (Z)-3-amino-3-(2-chloro-6-methylpyri-
din-3-yl)propenamide derivatives 1 into 2-(2-imino-
2,3-dihydropyrido[3,2-e]-1,3-thiazin-(Z)-4-ylidene)acet-
amide derivatives 3 was carried out as illustrated in
Scheme 1. Thus, the enamino amides 1 were treated with
2 molar amounts of sodium hydride in DMF at 0 °C. The
mixture was then allowed to react with a range of isothio-
cyanates to give the dianionic intermediates 2. Attack of
the sulfur atom on the 2-position of the pyridine ring af-
forded the pyridothiazine derivatives 3, after the usual
aqueous workup followed by purification using column
chromatography on silica gel, in fair to good yields
(Table 1). We were unable to detect the presence any trace
amounts of 2-(2-thioxopyrido[2,3-d]pyrimidin-4-ylid-
ene)acetamide derivatives 4, the products arising from the
attack of nitrogen on the 2-position of the pyridine ring.
The 13C NMR spectra of the products 3 showed signals at
about d = 165, assignable to imine carbons, and no signals
at about d = 200, which would be for thiocarbonyl carbons
of the compounds 4. The stereochemistry of the 4-ylidene
moiety of the products 3 was assigned to be Z. The Z-pref-
erence is ascribed to intramolecular hydrogen bonding be-
tween the H-3 of pyridothiazine ring and the amide
carbonyl. NOE experiments were carried out to confirm
the stereochemistry of compound 3a. Thus, irradiation of
Some compounds having the pyrido[3,2-e]-1,3-thiazine
skeleton have been reported to exhibit biological activi-
ties.2 However, there have been few reports on the meth-
ods for constructing this pyridothiazine system to date,
though Couture et al. have described a synthesis of 2-sub-
stituted 4H-pyrido[3,2-e]-1,3-thiazin-4-ones by reactions
of 2-chloropyridine-3-carboxamide with various O-ethyl
thiolates.3 A synthesis of 3,4-dihydro-2H-[1,3]thiazi-
no[6,5-b]quinolines by reaction of 3-aminomethyl-2-
chloroquinoline derivatives with isothiocyanates has been
reported by Kombarov et al.4 To the best of our knowl-
edge, the present 2-(2-imino-2,3-dihydropyrido[3,2-e]-
1,3-thiazin-4-ylidene)acetic acid skeleton, which carries a
carbon substituent at the 4-position of pyrido[3,2-e]-1,3-
thiazine ring, is unknown in the literature.
SYNTHESIS 2008, No. 11, pp 1703–1706
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x.
x
x
.
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0
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Advanced online publication: 11.04.2008
DOI: 10.1055/s-2008-1067015; Art ID: F01008SS
© Georg Thieme Verlag Stuttgart · New York

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K. Kobayashi et al.
PAPER
reference with a JEOL ECP500 FT NMR spectrometer operating at
500 MHz or a JEOL LA400 FT NMR spectrometer operating at 400
MHz. The 13C NMR spectra were determined in CDCl3 using TMS
as an internal reference with a JEOL ECP500 FT NMR spectrome-
ter operating at 125 MHz. Low-resolution MS spectra were mea-
sured by a JEOL JMS AX505 HA spectrometer. TLC was carried
out on a Merck Kieselgel 60 PF254. Column chromatography was
performed using Merck Kieselgel 60 (0.063–0.200 mm). All of the
organic solvents used in this study were dried over appropriate dry-
ing agents and distilled prior to use.
Table 1 Preparation of Pyridothiazine Derivatives 3
Entry
1
R2
3 (Yield, %)a
3a (72)
3b (71)
3c (65)
3d (74)
3e (73)
3f (73)
1
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1c
Ph
2
3-Tol
4-BrC6H4
Et
3
4
3-Amino-3-(2-chloro-6-methylpyridin-3-yl)acetamide derivatives
1a and 1b were prepared according to the procedure previously re-
ported by us.1 All other chemicals used in this study were commer-
cially available.
5
c-Hex
Bn
6
7
Ph
3g (70)
3h (68)
3i (69)
(Z)-3-Amino-3-(2-chloro-6-methylpyridin-3-yl)-1-(pyrrolidin-
1-yl)propenone (1c)
This compound was prepared from 2-chloro-6-methylpyridine-3-
carbonitrile and 1-acetylpyrrolidine by our previously reported pro-
cedure;1 yield: 64%; yellow oil; Rf = 0.41 (1:2 THF–C6H6).
8
3-Tol
Et
9
10
11
c-Hex
Ph
3j (63)
IR (neat): 3375, 3273, 3184, 1616 cm–1.
3k (73)
1H NMR (500 MHz, CDCl3): d = 1.84–1.95 (m, 4 H), 2.57 (s, 3 H),
3.37–3.43 (m, 2 H), 3.49–3.56 (m, 2 H), 4.74 (s, 1 H), 6.2–6.9 (br,
2 H), 7.13 (d, J = 7.8 Hz, 1 H), 7.62 (d, J = 7.8 Hz, 1 H).
a Isolated yield.
the signal at d = 5.68, assignable to the vinyl proton, re- Anal. Calcd for C13H16ClN: C, 58.76; H, 6.07; N, 15.81. Found: C,
58.64; H, 6.13; N, 15.93.
sulted in an enhancement (9.2%) of the signal at 7.86, as-
signable to the H-5 of the pyridothiazine ring. Although
one of the possible stereoisomers was obtained as a sole
product in each reaction, the stereochemistry of the 2-imi-
no moiety was not yet clarified.
N,N-Dimethyl-2-(7-methyl-2-phenylimino-2,3-dihydropyri-
do[3,2-e]-1,3-thiazin-(Z)-4-ylidene)acetamide (3a); Typical Pro-
cedure
To a stirred suspension of NaH (60% in oil; 23 mg, 0.58 mmol) in
DMF (2 mL) at 0 °C was added dropwise a solution of 1a (68 mg,
0.29 mmol) in DMF (2 mL). After 15 min, PhNCS (39 mg, 0.29
mmol) was added, and the stirring was continued for an additional
1 h at the same temperature. Sat. aq NH4Cl (10 mL) was added, and
the organic materials were extracted with CH2Cl2 (3 × 10 mL). The
combined extracts were washed with H2O (3 × 10 mL) and brine (10
The reactions using aliphatic isothiocyanates having d-hy-
drogen(s) (entries 4–6, 9, and 10) also successfully pro-
ceeded and the desired products were obtained in the
yields comparable to those using aromatic isothiocyanates
(entries 1–3, 7, 8, and 11). The use of the respective enam-
ino tert-butyl ester in place of the enamino amides 1 re- mL), and then dried (Na2SO4). Evaporation of solvent gave a resi-
due, which was purified by column chromatography on silica gel
sulted in the formation of intractable mixtures of products;
(1:2 EtOAc–hexane) to afford 3a.
however, we have no explanation for this.
Yellow solid; yield: 70 mg (72%); mp 221–223 °C (dec.) (hexane–
CH2Cl2).
IR (KBr): 3452, 1630, 1605 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.30 (s, 3 H), 3.06 (br s, 3 H), 3.15
(br s, 3 H), 5.68 (s, 1 H), 6.93 (d, J = 8.2 Hz, 1 H), 7.23 (dd, J = 7.3,
1.4 Hz, 2 H), 7.45 (tt, J = 7.3, 1.4 Hz, 1 H), 7.50 (t, J = 7.3 Hz, 2 H),
7.86 (d, J = 8.2 Hz, 1 H), 14.07 (br s, 1 H).
13C NMR (125 MHz, CDCl3): d = 24.66, 82.01, 109.86, 119.38,
128.17, 128.30, 129.00, 129.46, 131.80, 139.89, 142.28, 149.16,
161.98, 168.50, 175.63.
MS (EI, 70 eV): m/z (%) = 338 (45, [M+]), 292 (100).
The use of two molar amounts of sodium hydride is essen-
tial for the satisfactory production of the desired products.
For example, the reaction of 1a with phenyl isothiocyan-
ate using an equimolar amount of sodium hydride gave
only rather decreased yield (26%) of the product 2a, and
a considerable amount of the starting material was recov-
ered. The necessity of two molar amounts of sodium
hydride can be explained by the formation of the di-
anionic intermediate 2 as stated for the preparation of
(Z)-2-(2-oxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-
ylidene)acetamide derivatives in the previous paper.1
Anal. Calcd for C18H18N4OS: C, 63.88; H, 5.36; N, 16.56; S, 9.47.
Found: C, 63.87; H, 5.40; N, 16.77; S, 9.42.
In conclusion, we have developed a simple procedure for
the preparation of the novel pyridothiazine derivatives.
The present method may be valuable for organic synthesis
because of the ready availability of the starting materials
as well as the ease of operations.
N,N-Dimethyl-2-[7-methyl-2-(3-methylphenyl)imino-2,3-di-
hydropyrido[3,2-e]-1,3-thiazin-(Z)-4-ylidene]acetamide (3b)
Pale-yellow solid; mp 215 °C (dec.) (hexane–CH2Cl2).
IR (KBr): 3310, 1630, 1605 cm–1.
All melting points were obtained on a Laboratory Devices MEL-
TEMP II melting apparatus and are uncorrected. IR spectra were de-
termined with a Shimadzu FTIR-8300 spectrophotometer. The H
1H NMR (500 MHz, CDCl3): d = 2.32 (s, 3 H), 2.41 (s, 3 H), 3.06
(br s, 3 H), 3.15 (br s, 3 H), 5.67 (s, 1 H), 6.92 (d, J = 7.9 Hz, 1 H),
7.03 (d, J = 7.9 Hz, 1 H), 7.04 (s, 1 H), 7.25 (d, J = 7.9 Hz, 1 H),
7.38 (t, J = 7.9 Hz, 1 H), 7.85 (d, J = 7.9 Hz, 1 H), 14.02 (s, 1 H).
1
NMR spectra were determined in CDCl3 using TMS as an internal
Synthesis 2008, No. 11, 1703–1706 © Thieme Stuttgart · New York

PAPER
Synthesis of Pyridothizine Derivatives
1705
13C NMR (125 MHz, CDCl3): d = 21.41, 24.72, 81.87, 109.84,
119.30, 126.41, 128.69, 128.98, 129.95, 131.75, 138.82, 139.75,
142.32, 142.32, 149.20, 161.98, 168.52, 175.65.
2-(7-Methyl-2-phenylimino-2,3-dihydropyrido[3,2-e]-1,3-thi-
azin-(Z)-4-ylidene)-1-(morpholin-4-yl)ethanone (3g)
Pale-yellow solid; mp 273 °C (dec.) (hexane–CH2Cl2).
MS (EI, 70 eV): m/z (%) = 352 (62, [M+]), 306 (100).
IR (KBr): 3427, 1639, 1614 cm–1.
Anal. Calcd for C19H20N4OS: C, 64.75; H, 5.72; N, 15.90; S, 9.10.
Found: C, 64.54; H, 5.56; N, 15.70; S, 9.16.
1H NMR (500 MHz, CDCl3): d = 2.32 (s, 3 H), 3.67–3.79 (m, 8 H),
5.65 (s, 1 H), 6.93 (d, J = 7.9 Hz, 1 H), 7.23 (d, J = 7.3 Hz, 2 H),
7.45 (t, J = 7.3 Hz, 1 H), 7.51 (t, J = 7.3 Hz, 2 H), 7.86 (d, J = 7.9
Hz, 1 H), 13.91 (br s, 1 H).
MS (EI, 70 eV): m/z (%) = 380 (14, [M+]), 344 (50), 262 (53), 218
(100).
2-[2-(4-Bromophenyl)imino-7-methyl-2,3-dihydropyrido[3,2-
e]-1,3-thiazin-(Z)-4-ylidene]-N,N-dimethylacetamide (3c)
Yellow solid; mp 241–242 °C (dec.) (hexane–CH2Cl2).
IR (KBr): 3435, 1630, 1605 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.33 (s, 3 H), 3.06 (br s, 3 H), 3.15
(br s, 3 H), 5.69 (s, 1 H), 6.94 (d, J = 7.9 Hz, 1 H), 7.11 (d, J = 8.7
Hz, 2 H), 7.61 (d, J = 8.7 Hz, 2 H), 7.86 (d, J = 7.9 Hz, 1 H), 14.07
(br s, 1 H).
Anal. Calcd for C20H20N4OS: C, 63.14; H, 5.30; N, 14.73; S, 8.43.
Found: C, 62.05; H, 5.04; N, 14.62; S, 8.50.
2-[7-Methyl-2-(3-methylphenylimino)-2,3-dihydropyrido[3,2-
e]-1,3-thiazin-(Z)-4-ylidene]-1-(morpholin-4-yl)ethanone (3h)
Yellow solid; mp 262–263 °C (dec.) (hexane–CH2Cl2).
IR (KBr): 3448, 1628, 1606 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.33 (s, 3 H), 2.41 (s, 3 H), 3.67–
3.75 (m, 8 H), 5.64 (s, 1 H), 6.93 (d, J = 7.9 Hz, 1 H), 7.03 (d,
J = 7.3 Hz, 1 H), 7.04 (s, 1 H), 7.26 (d, J = 7.3 Hz, 1 H), 7.39 (t,
J = 7.3 Hz, 1 H), 7.85 (d, J = 7.9 Hz, 1 H), 13.89 (br s, 1 H).
13C NMR (125 MHz, CDCl3): d = 16.80, 20.12, 62.20, 76.31,
105.08, 114.08, 121.70, 124.12, 124.45, 125.24 (2 C), 127.17,
134.26, 135.03, 138.56, 144.57, 157.66, 162.71, 170.95.
MS (EI, 70 eV): m/z (%) = 416 (52, [M+]), 372 (100).
Anal. Calcd for C18H17BrN4OS: C, 51.80; H, 4.11; N, 13.43; S, 7.68.
Found: C, 51.78; H, 3.98; N, 13.33; S, 7.46.
2-(2-Ethylimino-7-methyl-2,3-dihydropyrido[3,2-e]-1,3-thi-
azin-(Z)-4-ylidene)-N,N-dimethylacetamide (3d)
Orange solid; mp 207 °C (dec.) (hexane–CH2Cl2).
IR (KBr): 3442, 1622, 1603 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.33 (t, J = 7.3 Hz, 3 H), 2.57 (s,
3 H), 3.04 (br s, 3 H), 3.11 (br s, 3 H), 4.81 (q, J = 7.3 Hz, 2 H), 5.57
(s, 1 H), 6.95 (d, J = 7.9 Hz, 1 H), 7.82 (d, J = 7.9 Hz, 1 H), 13.81
(br s, 1 H).
MS (EI, 70 eV): m/z (%) = 394 (60, [M+]), 306 (100).
Anal. Calcd for C21H22N4OS: C, 63.94; H, 5.62; N, 14.20; S, 8.13.
Found: C, 63.75; H, 5.52; N, 14.08; S, 8.40.
MS (EI, 70 eV): m/z (%) 290 (100, [M+]).
2-(2-Ethylimino-7-methyl-2,3-dihydropyrido[3,2-e]-1,3-thi-
azin-(Z)-4-ylidene)-1-(morpholin-4-yl)ethanone (3i)
Yellow solid; mp 240–242 °C (dec.) (hexane–CH2Cl2).
Anal. Calcd for C14H18N4OS: C, 57.91; H, 6.25; N, 19.29; S, 11.04.
Found: C, 57.62; H, 5.95; N, 19.17; S, 11.27.
2-(2-Cyclohexylimino-7-methyl-2,3-dihydropyrido[3,2-e]-1,3-
thiazin-(Z)-4-ylidene)-N,N-dimethylacetamide (3e)
Yellow solid; 154 °C (dec.) (hexane–CH2Cl2).
IR (KBr): 3435, 1630, 1605 cm–1.
IR (KBr): 3431, 1629, 1611 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.33 (t, J = 7.0 Hz, 3 H), 2.57 (s,
3 H), 3.64–3.73 (m, 8 H), 4.80 (q, J = 7.0 Hz, 2 H), 5.53 (s, 1 H),
6.95 (d, J = 8.1 Hz, 1 H), 7.81 (d, J = 8.1 Hz, 1 H), 13.68 (br s, 1 H).
1H NMR (500 MHz, CDCl3): d = 0.87–1.87 (m, 9 H), 2.56 (s, 3 H),
2.75–2.77 (m, 1 H), 3.04 (br s, 3 H), 3.10 (br s, 3 H), 5.53 (s, 1 H),
5.93–5.98 (m, 1 H), 6.93 (d, J = 8.2 Hz, 1 H), 7.79 (d, J = 8.2 Hz, 1
H), 13.81 (br s, 1 H).
MS (EI, 70 eV): m/z (%) = 332 (85, [M+]), 246 (100).
Anal. Calcd for C16H20N4O2S: C, 57.81; H, 6.06; N, 16.85; S, 9.65.
Found: C, 57.45; H, 5.95; N, 16.86; S, 9.60.
13C NMR (125 MHz, CDCl3): d = 24.37, 25.71, 26.64 (2 C), 29.21,
80.76, 111.25, 119.01, 131.94, 142.18, 147.99, 155.50, 160.59,
168.64, 175.79.
2-(2-Cyclohexylimino-7-methyl-2,3-dihydropyrido[3,2-e]-1,3-
thiazin-(Z)-4-ylidene)-1-(morpholin-4-yl)ethanone (3j)
Yellow solid; mp 216–218 °C (hexane–CH2Cl2).
MS (EI, 70 eV): m/z (%) = 344 (51, [M+]), 262 (55), 218 (100).
IR (KBr): 3448, 1628, 1605 cm–1.
Anal. Calcd for C18H24N4OS: C, 62.76; H, 7.02; N, 16.26; S, 9.31.
Found: C, 62.50; H, 7.27; N, 16.06; S, 9.19.
1H NMR (400 MHz, CDCl3): d = 0.87–1.87 (m, 9 H), 2.56 (s, 3 H),
2,75–2.78 (m, 1 H), 3.63–3.72 (m, 8 H), 5.50 (s, 1 H), 5.91–5.99 (m,
1 H), 6.93 (d, J = 8.1 Hz, 1 H), 7.77 (d, J = 8.1 Hz, 2 H), 13.17 (br
s, 1 H).
2-(2-Benzylimino-7-methyl-2,3-dihydropyrido[3,2-e]-1,3-thi-
azin-(Z)-4-ylidene)-N,N-dimethylacetamide (3f)
Pale-yellow solid; mp 232–233 °C (dec.) (hexane–CH2Cl2).
IR (KBr): 3438, 1628, 1602 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.50 (s, 3 H), 3.05 (br s, 3 H), 3.11
(br s, 3 H), 5.59 (s, 1 H), 6.02 (s, 2 H), 6.91 (d, J = 7.9 Hz, 1 H), 7.21
(t, J = 7.3 Hz, 1 H), 7.27 (t, J = 7.3 Hz, 2 H), 7.54 (d, J = 7.3 Hz, 2
H), 7.80 (d, J = 7.9 Hz, 1 H), 13.91 (br s, 1 H).
MS (EI, 70 eV): m/z (%) = 386 (49, [M+]), 304 (51), 218 (100).
Anal. Calcd for C20H26N4O2S: C, 62.15; H, 6.78; N, 14.50; S, 8.30.
Found: C, 61.88; H, 6.91; N, 14.35; S, 8.27.
2-(7-Methyl-2-phenylimino-2,3-dihydropyrido[3,2-e]-1,3-thi-
azin-(Z)-4-ylidene)-1-(pyrrolidin-1-yl)ethanone (3k)
Pale-yellow solid; mp 274 °C (dec.) (hexane–CH2Cl2).
13C NMR (125 MHz, CDCl3): d = 24.53, 49.58, 81.48, 110.45,
119.32, 127.03, 128.04, 128.55 (2 C), 131.94, 137.44, 141.96,
147.30, 161.70, 168.54, 175.22.
IR (KBr): 3417, 1634, 1604 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.90–1.94 (m, 2 H), 2.01–2.04 (m,
2 H), 2.31 (s, 3 H), 3.55–3.60 (m, 4 H), 5.52 (s, 1 H), 6.92 (d, J = 7.8
Hz, 1 H), 7.23 (d, J = 7.3 Hz, 2 H), 7.44 (t, J = 7.3 Hz, 1 H), 7.50 (t,
J = 7.3 Hz, 2 H), 7.85 (d, J = 7.8 Hz, 1 H), 14.05 (br s, 1 H).
MS (EI, 70 eV): m/z (%) = 352 (100, [M+]).
Anal. Calcd for C19H20N4OS: C, 64.75; H, 5.72; N, 15.90; S, 9.10.
Found: C, 64.73; H, 5.80; N, 15.66; S, 9.02.
MS (EI, 70 eV): m/z (%) = 364 (58, [M+]), 292 (12), 252 (100).
Synthesis 2008, No. 11, 1703–1706 © Thieme Stuttgart · New York

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K. Kobayashi et al.
PAPER
Anal. Calcd for C20H20N4OS: C, 65.91; H, 5.53; N, 15.37; S, 8.80.
Found: C, 65.65; H, 5.61; N, 15.14; S, 8.53.
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Y.; Shishikura, J.; Inami, H.; Yatsugi, S.; Okada, M.;
Sakamoto, S.; Yamaguchi, T. J. Pharmacol. Exp. Ther.
2003, 306, 66. (c) Yamashita, H.; Ohno, K.; Amada, Y.;
Hattori, H.; Ozawa-Funatsu, Y.; Toya, T.; Inami, H.;
Shishikura, J.; Okada, M.; Yamaguchi, T. J. Pharmacol.
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Imai, H.; Shishikura, J.; Sakamoto, S.; Okada, M.;
Yamaguchi, T. Eur. J. Pharmacol. 2004, 494, 147; and
references cited therein.
Acknowledgment
Determination of mass spectra and performance of combustion
analyses by Mrs. Miyuki Tanmatsu of this Faculty are gratefully
acknowledged.
References
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Synthesis 2008, No. 11, 1703–1706 © Thieme Stuttgart · New York