Efficient access to novel mono- and disubstituted pyrido[3,2-d]pyrimidines

Article abstract of DOI:10.1055/s-2006-947350

New mono- and disubstituted pyrido[3,2-d]pyrimidines were synthesized starting from the corresponding 2,4-dichloro derivative through S_NAr and palladium-catalyzed reactions. S_NAr and palladium-catalyzed hydro-deshalogenation occurred

Full text of DOI:10.1055/s-2006-947350

1938
LETTER
Efficient Access to Novel Mono- and Disubstituted Pyrido[3,2-d]pyrimidines
Efficient
A
ccessto
b
N
ovel Mon
d
o- and
D
isub
e
stitutedPyr
l
ido[3,2
l
-
d
]pyr
a
imidines tif Tikad,a,b Sylvain Routier,*a Mohamed Akssira,b Jean-Michel Leger,c Christian Jarry,c Gérald Guillaumeta
a
ICOA UMR 6005 CNRS, Université d’Orléans, 45067, Orléans, France
Fax +33(2)38417281; E-mail: sylvain.routier@univ-orleans.fr
b
c
LCBA Université Hassan II-Mohammedia, BP 146, 20650 Mohammedia, Morocco
EA 2962, Pharmacochimie, Université Victor Segalen Bordeaux II, France
Received 27 April 2006
O
R2
6 R1 = R2 = Cl
Abstract: New mono- and disubstituted pyrido[3,2-d]pyrimidines
were synthesized starting from the corresponding 2,4-dichloro de-
rivative through SNAr and palladium-catalyzed reactions. SNAr and
palladium-catalyzed hydro-deshalogenation occurred selectively at
position C-4. Further Suzuki cross-coupling led to C-2 and C-2,4
mono- and disubstituted compounds.
N
I R2 = Cl, R1 = H, NHR, OR, SR
II R2 = Aryl, R1 = NHR, OR, SR
III R2 = Aryl, R1 = H
O
N
N
N
O
R1
1
Figure 1
Key words: pyrimidines, palladium, Suzuki, SNAr, selectivity
First we developed an original synthesis of the 2,4-dichlo-
ropyrido[3,2-d]pyrimidine (6) with a high yield from a
commercially 2,3-pyridinedicarboxylic anhydride (1,
Scheme 1).9,10 The first step consisted in a methanolysis,
carried out in refluxing MeOH to afford, after recrystalli-
zation in a small amount of EtOAc, the pure regioisomer
2 in a 72% yield.11 A further multistep sequence led to the
isocyanate 3 from compound 2.
Polyaza heterocycles such as diazines are largely used in
the design of biologically active structures.1 Recently, the
quinoxaline heterocycle was included in anticancer selec-
tive kinase inhibitors acting at the ATP binding site. This
strategy led to ZD 1839 (Gefitinib, Iressa®) and PD
173074, which both exhibited strong antiangiogenic ac-
tivities.2,3 Pyridopyrimidines, nitrogen isosteres of the
previously evocated heterocycles, were claimed to have
medicinal applications too.4 In particular, the recent de-
velopment of anticancer agents led to some pyrido[2,3-
d]pyrimidines analogues as PD 166285 and VK 19911,
which were described as very promising PDGF and MAP
kinase inhibitors, respectively.5,6
O
CO2H
NCO
b
a
O
N
CO2CH3
72%
N
N
CO2CH3
O
c
H
N
H
O
N
O
N
Cl
d
For the reasons given above, the synthesis of pyrido-
pyrimidine derivatives provided an interesting challenge.
Construction of functionalized pyridopyrimidines in-
volved cyclization of appropriately substituted pyrim-
idines or pyridines whose synthesis was not always easy.
In particular the synthesis of the pyrido[3,2-d]pyrimidines
type remains very complicated and hardly cited in the
literature.
e
NH
N
N
N
PMB
N
O
O
Cl
4
71%
6
quant.
58%
5
Scheme 1 Reagents and conditions: a) dry MeOH, reflux, 48 h; b)
i) ClCO2Et (1.5 equiv), Et3N (1.3 equiv), –10 °C, 1.5 h; ii) NaN3 (1.7
equiv) in H2O, –10 °C to 0 °C, 1.5 h; iii) r.t. and aqueous treatment
then toluene, reflux, 2 h; c) PMBNH2 (1 equiv), pyridine–toluene 1:1,
reflux, 24 h; d) AlCl3 (10 equiv), anisole, r.t., 2 h; e) PCl5 (4 equiv),
POCl3, reflux, 4 h.
Many publications reported the synthesis of polysubstitut-
ed pyridopyrimidines and most of them concerned the
pyridine ring.4,7 In this work, we described the novel
method of synthesis of 2,4-dichloropyrido[3,2-d]pyrimi-
dine. It is the only compound described in the literature
starting from the 3-aminopicolinic acid in a 9% yield,8
which was then used in regioselective reactions with
nucleophiles and Suzuki or Stille palladium cross cou-
pling reactions in order to design compounds type I–III
(Figure 1). All our investigations showed clearly regio-
selective attack of nucleophilic agent and palladium
catalyst.
Only degradation products were obtained when the non-
isolated intermediate 3 was reacted with ammonia. On the
other hand, direct reaction of 3 with the p-methoxybenzyl-
amine conducted in a refluxing mixture of pyridine and
toluene to the dione 4 in a 71% overall yield from 2
(Scheme 1).12 One of the deprotection method to remove
the PMB group involved the presence of TFA but led only
to the starting material.13 The high insolubility of com-
pound 4 in most of organic solvent prevented all classical
reaction including the use of CAN. Finally, the reaction
was achieved in anisole using a large AlCl3 excess (10
equiv) in a quantitative yield.14 The double chlorination of
5 was achieved by a complex mixture of PCl5 in refluxing
POCl3 as already reported in the literature.8 In our hands
SYNLETT 2006, No. 12, pp 1938–1942
0
1
.0
8
.2
0
0
6
Advanced online publication: 24.07.2006
DOI: 10.1055/s-2006-947350; Art ID: G13706ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Efficient Access to Novel Mono- and Disubstituted Pyrido[3,2-d]pyrimidines
1939
the yield in isolated product 6 stayed to 58% (29% overall aryl boronic acids. All reactions required only 5 mol% of
yield starting from anhydride 1).15
catalyst and Na2CO3 in a mixture of DME and water at
75 °C. All the reactions were stopped when the starting
material completely disappeared to afford, after purifica-
tion by flash silica gel chromatography, the expected
products 10–24.25 The yield in isolated products oscillated
between 68% and 98% in only a few hours. The substitu-
tion of the starting material by the NH-, O- or S-isopropyl
groups did not affect the yield of the coupling reactions,
which appeared as very homogeneous (entries 4–6 com-
paring to 7–9, 10–12, and 13–15).
No significant effect on the yield was observed either by
varying the amount of PCl5 or by increasing the reaction
time. Based on our knowledge in the pyrido[2,3-d]pyrim-
idine series, we tried the same reaction in refluxing
POCl3.16 After four hours, the starting material was fully
recovered. Adding a base such as N,N-diethylaniline,17
Et3N or pyridine gave similar results.18,19 Conversely, the
introduction of DBU or DMF led only to degradation.20,21
Then, nucleophilic substitutions of aromatic chlorine
were investigated. In an older report, the authors related
that the reaction of 6 with concentrated NH4OH occurred
in the more reactive position C-4 rather than in C-2. The
authors suggested that the reactions currently occurred as
described using quinoxalines or pyrido[2,3-d]pyrim-
idines.8,22 Nevertheless, no analysis or direct proof of its
regioselectivity was available to our knowledge.8
In addition, substitution in each o-, m- and p-position of
the boronic acid by the electron donor methoxy group had
no effect on the yields. As a new proof of high efficiency,
the reaction time was limited to 4 hours and our strategy
also appeared again as very attractive. Compounds 22–24
were next synthesized from the heteroatomic 2-thio-
pheneboronic acid in very good yields. In the presence of
heteroaryl groups, the catalytic cycle and also the reaction
time were not affected. This new interesting result
prompted us to explore the reaction with other hetero-
cycles.
Hence, compound 6 was treated with a stoichiometric
amount of isopropylamine in the presence of Et3N in dry
THF at room temperature (Scheme 2, Table 1, entry 1) to
afford compound 7 in a near quantitative yield. Then, only
one equivalent of isopropanol was used in the presence of
NaH. The in situ formed sodium isopropanolate reacted
with 6 to afford the only one regioisomer 8 in a 70% yield.
The same reaction was conducted with the propan-2-thiol
to give compound 9 in a 88% yield (Table 1, entry 3).23 In
addition, this compound could be obtained in a 91% yield
from 6 and the lithium salt of the propan-2-thiol at –20 °C.
The strong difference between the two chlorine atoms of
6 with nucleophiles prompted us to explore next other se-
lectivity. So we next raised the idea to use 6 in selective
palladium cross-coupling reactions. The first assay was
realized with 3-methoxyphenylboronic acid under the
previously evocated conditions. After three hours, the
1
starting material was fully consumed but H NMR re-
vealed the presence of a complex mixture, due to several
unselective reactions. This result revealed nevertheless
indicated a palladium insertion into the C–Cl bonds.
N
R
N
Cl
b
N
N
N
N
So, varying the conditions, we performed a dechlorination
in C-4 position (Scheme 2) with Bu3SnH as reagent in
toluene with Pd(PPh3)4.26 Compound 25 was isolated after
only one hour in a 86% yield.27 For information, direct
reaction Bu3SnH without any Pd(PPh3)4 also failed and
the starting material 6 was fully recovered. The structure
a
c
N
Cl
X
X
10–24
7–9
N
N
Cl
N
Cl
N
N
R
d
6
N
N
N
1
of compound 25 was characterized by H NMR, COSY
26–30
25
86%
experiment and C–H correlation. H4–C4 and H6–C6 and
H8–C8 were clearly identified. The long-range C,H corre-
lations HMBC NMR spectroscopy confirmed a direct
relation between H4, C4a, C8a and H6, C4a, C8 and also
Scheme 2 Reagents and conditions: a) for X = NH, Et3N (1.05
equiv), for X = O, S, NaH (1.05 equiv), THF, 0 °C to r.t., 12 h; (b)
boronic acid (1.2 equiv), Pd(PPh3)4 (5 mol%), Na2CO3 (2 equiv),
DME–H2O 2:1, 75 °C; (c) Bu3SnH (1.1 equiv), toluene, Pd(PPh3) 4 (5 confirmed the structure of 25. Our new synthetic sequence
mol%), 100 °C, 1 h; (d) boronic acid (1.1 equiv), Pd(PPh3)4 (5 mol%),
Na2CO3 (2 equiv), toluene–EtOH 2:1, 100 °C.
involving the regioselective palladium-catalyzed reduc-
tion of the bis-chlorinated compound 6, provided also the
rare 2-chloropyrido[3,2-d]pyrimidine (25).
All SNAr were also similarly performed in very good
yields at low temperature with only a stoichiometric
As an extension, the residual chlorine atom on compound
25 was displaced with phenylboronic acid, 2- and 3-
amount of nucleophile. These results indicated also the
methoxy phenylboronic acids in DME–H2O to give the
high reactivity of the chlorine atom in position 4 of the
targeted compounds 26–28 with the low yields of 11–
31%. Fortunately, using toluene and EtOH increased
considerably the yields towards 86%, 80% and 84% re-
spectively (Table 2, entries 1–3). One more time, the
pyrido[3,2-d]pyrimidine skeleton. In order to formally
establish the regioselectivity of SNAr in position C-4 of
the 2,4-dichloropyrido[3,2-d]pyrimidine (6), an X-ray
analysis of 9 was performed.24
reactions appeared as clean and very efficient. Based
Compounds 7–9 were next reacted through a Suzuki-type on our knowledge, this method constituted the more
reaction first carried out using a 1.2 equivalents of various easily access to such 2-(het)aryl-pyrido[3,2-d]pyrim-
Synlett 2006, No. 12, 1938–1942 © Thieme Stuttgart · New York

1940
A. Tikad et al.
LETTER
Table 1 Synthesis of Disubstituted Pyrido[3,2-d]pyrimidines in Positions C-2 and C-4
Entry
Structure
X
Time (h)
Product (yield, %)
N
Cl
1
2
3
NH
O
S
12
12
12
7 (96)
8 (70)
9 (88)
N
N
N
N
N
N
N
N
X
N
X
4
5
6
NH
O
S
4
1
1
10 (84)
11 (88)
12 (90)
N
X
7
8
9
NH
O
S
1
1
1
13 (88)
14 (98)
15 (89)
OMe
N
X
10
11
12
NH
O
S
4
2
3
16 (86)
17 (87)
18 (81)
OMe
OMe
N
X
13
14
15
NH
O
S
3
3
3
19 (78)
20 (68)
21 (85)
N
N
S
N
X
16
17
18
NH
O
S
4
2
3
22 (87)
23 (94)
24 (73)
N
N
idines 26–30 independently of the (het)arylboronic acid
nature and its substitution.
Table 2 Synthesis of 2-Chloropyrido[3,2-d]pyrimidines Sub-
stituted in Position C-2
In this preliminary work, we described the chemical inter-
est of the 2,4-dichloropyrido[3,2-d]pyrimidine. SNAr and
Suzuki or Stille palladium cross-coupling reactions were
achieved successively and regioselectively. SNAr and re-
duction occurred first in the C-4 more reactive position. A
facile access to a C-2 mono halogenated compound was
also found. It could be used in supplementary cross
Suzuki reactions. Studies are also in progress to general-
ize this strategy, which provides an efficient access to var-
ious mono- and disubstituted pyrido[3,2-d]pyrimidines at
positions C-2 and C-4 by successive or tandem palladium-
catalyzed reactions.
Entry
R
Time
(h)
Product (yield, %)
Solvent:
Solvent:
DME–H2O
toluene–EtOH
1
2
3
4
5
Ph
3
4
4
4
2
26 (18)
27 (31)
28 (11)
–
26 (86)
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
2-Thiophene
27 (80)
28 (84)
29 (88)
–
30 (85)
Synlett 2006, No. 12, 1938–1942 © Thieme Stuttgart · New York

LETTER
Efficient Access to Novel Mono- and Disubstituted Pyrido[3,2-d]pyrimidines
1941
(13) (a) Miki, Y.; Hachiken, H.; Kashima, Y.; Sugimura, W.;
Yanase, N. Heterocycles 1998, 48, 1. (b) Joseph, B.;
Behard, A.; Lesur, B.; Guillaumet, G. Synlett 2003, 1542.
(14) Akiyama, T.; Kumegawa, M.; Takesue, Y.; Nishimoto, H.;
Ozaki, S. Chem. Lett. 1990, 3, 339.
Acknowledgment
We thank the Cancéropôle Grand Ouest and the Association pour la
Recherche contre le Cancer (ARC) for the financial support.
(15) Preparation of 6.
References and Notes
A mixture of 1H,3H-pyrido[3,2-d]pyrimidine-2,4-dione (5,
1 g, 5 mmol), POCl3 (10 mL) and PCl5 (5.41 g, 4 equiv) was
refluxed for 4 h then cooled to r.t. Excess POCl3 was
evaporated and the residue neutralized with aq Na2CO3 and
extracted with CH2Cl2. The combined organic layers were
dried over MgSO4, and concentrated in vacuo. The residue
was purified by flash chromatography (PE–EtOAc, 8:2) to
afford compound 6 as a pale yellow solid (58% yield); mp
168–169 °C. IR (KBr): 3068, 1537, 1462, 1443, 1369, 1186,
1107, 878, 831, 794 cm–1. 1H NMR (250 MHz, CDCl3): d =
7.92 (dd, 1 H, J = 4.1, 8.5 Hz, H7), 8,33 (dd, 1 H, J = 1.6, 8.5
Hz, H8), 9.14 (dd, 1 H, J = 1.6, 4.1 Hz, H6) ppm. 13C NMR
(62.5 MHz, CDCl3): d = 130.3 (CH), 136.3 (CH), 137.1
(Cq), 149.0 (Cq), 153.2 (CH), 155.8 (Cq), 166.2 (Cq) ppm.
HRMS (EI-MS): m/z calcd for C7H335Cl2N3: 198.9704;
found: 198.9715.
(1) (a) Handratta, V. D.; Vasaitis, T. S.; Njar, V. C. O.; Gediya,
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E.; O’Neill, E. A.; Schwartz, C. D.; Thompson, C. M.;
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Tetrahedron Lett. 2005, 46, 5851.
(17) Gupta, M.; Nair, V. Tetrahedron Lett. 2005, 46, 1165.
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Tetrahedron Lett. 2003, 44, 7533.
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(11) Kenyon, J.; Thaker, K. J. Chem. Soc. 1957, 2531.
(12) Synthesis of 4.
A solution containing the 2,3-pyridine-carboxylic acid 2-
methylester (2, 5 g, 27.62 mmol) and Et3N (5.05 mL, 1.3
equiv, 35.90 mmol) in dry THF (100 mL) was cooled at
–10 °C. Ethyl chloroformate (3.96 ml, 1.5 equiv, 41.33
mmol) was added dropwise and the reaction mixture was
stirred at this temperature for 1.5 h. A solution of NaN3 (3.05
g, 1.7 equiv, 46.95 mmol) in H2O (35 mL) was then added in
one portion. After 1.5 h at 0 °C, the resulting heterogeous
mixture was filtered, the organic solvent was removed under
reduced pressure and the aqueous phase was extracted with
EtOAc (3 × 50 mL). The combined organic layers were
dried over MgSO4, and concentrated in vacuo. The crude
acyl azide was next dissolved in toluene (30 mL) and the
solution was refluxed for 2 h. After cooling to r.t., a solution
of 4-methoxybenzylamine (3.6 mL, 1 equiv, 27.62 mmol) in
pyridine (30 mL) was added and the reaction mixture was
refluxed for 24 h. The dark red solution was else evaporated
to dryness and the residue was washed with EtOH (2 × 50
mL) and filtered to obtain compound 4 as a white solid (71%
yield); mp 328–330 °C. IR (KBr): 3368, 3059, 2853, 1710,
1672, 1401, 1247, 809, 691 cm –1. 1H NMR (250 MHz,
DMSO-d6): d = 3.70 (s, 3 H, OCH3), 5.02 (s, 2 H, CH2), 6.86
(d, 2 H, J = 8.5 Hz, HAr), 7.30 (d, 2 H, J = 8.5 Hz, HAr), 7.57–
7.67 (m, 2 H, HPy), 8.49 (dd, 1 H, J = 1.6, 4.1 Hz, H6), 11.57
(s, 1 H, NH, exchangeable D2O) ppm. 13C NMR (62.5 MHz,
DMSO-d6) d = 42.7 (CH2), 54.7 (CH3), 113.4 (2 CH), 123.4
(CH), 128.6 (CH), 128.9 (Cq), 129.0 (2 CH), 130.5 (Cq),
136.5 (Cq), 144.8 (CH), 149.4 (Cq), 158.1 (CO), 160.2 (CO)
ppm. HRMS (EI-MS): m/z calcd for C15H13N3O3: 283.0956;
found: 283.0967.
(23) Preparation of 9.
A solution containing the 2,4-dichloropyrido[3,2-d]pyrimi-
dine (6, 500 mg, 2.5 mmol) in dry THF (25 mL) was cooled
at 0 °C. Then, a prebuilt suspension of 2-propanethiol (0.232
mL, 1 equiv) and NaH (105 mg, 60% in oil, 1.05 equiv) in
dry THF (15 mL) was dropwise added. The reaction mixture
was allowed to r.t. and stirred overnight. Hydrolysis was
realized with cold H2O (30 mL) and the aqueous layers were
extracted with EtOAc (3 × 20 mL). The combined organic
layers were dried on MgSO4, filtered and evaporated under
reduced pressure. The crude residue was purified by silica
gel column chromatography (PE–EtOAc, 8:2) to afford
compound 9 (88% yield); mp 93–94 °C. IR (KBr): 2963,
1555, 1518, 1458, 1426, 1334, 1169, 1110, 876, 853, 821,
720 cm–1. 1H NMR (250 MHz, CDCl3): d = 1.48 (d, 6 H,
J = 6.9 Hz, 2 CH3), 4.18 (m, 1 H, J = 6.9 Hz, CH), 7.73 (dd,
1 H, J = 4.1, 8.5 Hz, H7), 8.11 (dd, 1 H, J = 1.6, 8.5 Hz, H8),
8.84 (dd, 1 H, J = 1.6, 4.1 Hz, H6) ppm. 13C NMR ( 62.5
MHz, CDCl3): d = 22.6 (2 CH3), 35.3 (CH), 129.1 (CH),
135.9 (CH), 137.9 (Cq), 145.1 (Cq), 150.3 (CH), 156.5 (Cq),
178.1 (Cq) ppm. HRMS (EI-MS): m/z calcd for
C10H1035ClN3S: 239.02840; found: 239.0273.
(24) Diffraction data were collected using a CAD4 Enraf-Nonius.
Full crystallographic results have been deposited as
Supplementary Materials at the Cambridge Crystallographic
Data Centre, University Chemical Lab, 12 Union Road,
Cambridge CB2 1EZ UK; e-mail: deposit@ccdc.cam.ac.uk.
(25) Preparation of 21.
To a solution of 2-chloro-4-isopropylsulfanylpyrido[3,2-
d]pyrimidine (9, 100 mg, 0.42 mmol) in DME (6 mL) were
Synlett 2006, No. 12, 1938–1942 © Thieme Stuttgart · New York

1942
A. Tikad et al.
LETTER
successively added 4-methoxyphenylboronic acid (76 mg,
1.2 equiv) and a solution of Na2CO3 (89 mg, 2 equiv) in H2O
(3 mL) and Pd(PPh3)4 (24 mg, 0.05 equiv). The reaction
mixture was heated at 75 °C under vigorous stirring under
argon atmosphere. After complete disappearance of 9, the
solution was concentrated in vacuo and the residue diluted in
H2O (10 mL). After extraction with CH2Cl2 (3 × 20 mL), the
dried organic layers were evaporated to dryness. The crude
material was purified by flash column chromatography (PE–
CH2Cl2, 3:7) to afford compound 21 as a white solid (85%
yield); mp 125–126 °C. IR (KBr): 2954, 1600, 1587, 1536,
1458, 1435, 1376, 1165, 839, 821, 747, 696 cm–1. 1H NMR
(250 MHz, CDCl3): d = 1.58 (d, 6 H, J = 6.9 Hz, 2 CH3), 3.86
(s, 3 H, OCH3), 4.33 (m, 1 H, J = 6.9 Hz, CH), 7,00 (d, 2 H,
J = 8.8 Hz, H3¢), 7.65 (dd, 1 H, J = 4.1, 8.5 Hz, H7), 8.17 (dd,
1 H, J = 1.0, 8.5 Hz, H8), 8.53 (d, 2 H, J = 8.8 Hz, H2¢), 8.78
(dd, 1 H, J = 1.0, 4.1 Hz, H6) ppm. 13C NMR (62.5 MHz,
CDCl3): d = 22.7 (2 CH3), 34.6 (CH), 55.4 (CH3), 113.9
(CH), 128.3 (CH), 130.2 (Cq), 130.5 (CH), 136.6 (CH),
138.0 (Cq), 144.4 (Cq), 149.0 (CH), 159.5 (Cq), 162.1 (Cq),
173.8 (Cq). HRMS (EI-MS): m/z calcd for C17H17N3OS:
311.10923; found: 311.1116.
(27) Synthesis of 25.
A solution of 2,4-dichloropyrido[3,2-d]pyrimidine (6, 1.0 g,
5 mmol), Bu3SnH (1.48 mL, 1.1 equiv, 5.5 mmol) in toluene
(60 mL) was degassed by argon bubbling during 30 min.
Then, Pd(PPh3)4 (290 mg, 0.05 equiv, 0.25 mmol) was added
in one portion and the reaction mixture was placed in a pre-
heated oil 100 °C for 1 h. After cooling to r.t., the solvent
was evaporated in vacuo and a sat. solution of KF (20 mL)
was added. After filtration, the aqueous layers were
extracted with EtOAc (3 × 25 mL). The combined organic
layers were dried over MgSO4, and concentrated in vacuo.
The crude material was purified by flash chromatography
(PE–EtOAc, 8:2) to afford compound 25 as a white solid
(86% yield); mp 119–120 °C. IR (KBr): 3059, 1560, 1462,
1439, 1359, 1154, 1098, 873, 822, 696 cm–1. 1H NMR (250
MHz, CDCl3): d = 7.89 (dd, 1 H, J = 4.1, 8.5 Hz, H7), 8.32
(d, 1 H, J = 8.5 Hz, H8), 9.11 (dd, 1 H, J = 1.6, 4.1 Hz, H6),
9.54 (s, 1 H, H4) ppm. 13C NMR (62.5 MHz, CDCl3): d =
129.5 (CH, C7), 135.6 (CH, C8), 139.2 (Cq, C4a), 148.6 (Cq,
C8a), 153.0 (CH, C6), 158.0 (Cq, C2), 164.6 (CH, C4) ppm.
HRMS (EI-MS): m/z calcd for C7H4N335Cl: 165.00937;
found: 165.0104.
(26) Aboul-Fadl, T.; Löber, S.; Gmeiner, P. Synthesis 2000,
1727.
Synlett 2006, No. 12, 1938–1942 © Thieme Stuttgart · New York