Microwave enhanced Suzuki coupling: A diversity-oriented approach to the synthesis of highly functionalised 3-substituted-2-aryl/heteroaryl imidazo[4,5-b]pyridines

Article abstract of DOI:10.1016/j.tetlet.2011.12.051

A modified approach for the synthesis of 3-substituted 2-aryl/heteroaryl imidazo[4,5-b]pyridines utilising palladium catalysed cross-coupling reactions under microwave enhanced conditions has been achieved. utilisation of (A- ^taphos)₂

Full text of DOI:10.1016/j.tetlet.2011.12.051

Tetrahedron Letters 53 (2012) 1036–1041
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Microwave enhanced Suzuki coupling: a diversity-oriented approach
to the synthesis of highly functionalised 3-substituted-2-aryl/heteroaryl
imidazo[4,5-b]pyridines
Ayyiliath M. Sajith a, A. Muralidharan a,b,
⇑
a School of Chemical Sciences, Govt. College Kasargod, Kannur University, India
b Organic Chemistry Division, School of Chemical Sciences, Nehru Arts and Science College, Kannur University, Kannur, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 25 July 2011
Revised 8 December 2011
Accepted 12 December 2011
Available online 16 December 2011
A modified approach for the synthesis of 3-substituted 2-aryl/heteroaryl imidazo[4,5-b]pyridines utilis-
ing palladium catalysed cross-coupling reactions under microwave enhanced conditions has been
achieved. utilisation of (A-taphos)2PdCl2-catalysed cross-coupling reactions enables rapid derivatization
of this (imidazo[4,5-b]pyridines) pharmaceutically relevant core. This catalytic system is compatible with
a broad spectrum of arylboronic acids—electron rich, electron poor, and heteroarylboronic acids.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Microwave
Imidazo[4,5-b]pyridine
Suzuki coupling
Boronic acids
The synthesis of imidazo[4,5-b]pyridine based structures has
attracted attention in recent years due to their variety of biological
and pharmacological properties. Compounds incorporating this
heterocyclic ring can be considered as structural analogues of pur-
ines1 and are of interest as biologically active compounds. The het-
erocycles derived from these intermediates have recently been
evaluated as antagonists of various biological receptors, including
angiotensionII,2 platelet activating factor (PAF)3 and metabotropic
glutamate subtype V.3 Substituted imidazo[4,5-b]pyridines have
also been tested for their potential as anticancer,4 inotropic5 and
as selective antihistamine agents.6 Imidazo[4,5-b]pyridine deriva-
tives were also reported as Aurora kinases,7 and cyclic PDE inhibi-
tors. These data stimulated our studies on the synthesis of
substituted imidazo[4,5-b]pyridine derivatives.
The most common methods to access these compounds are from
2,3-diaminopyridines and these diamines are condensed with
carboxylic acids (or treated with an aldehyde in presence of an
oxidant).7–10 The synthesis of 3-substituted-2-aryl/heteroaryl
imidazo[4,5-b]pyridines from N2-substitutedpyridine-2,3-diamine
and carboxylic acids utilising polyphosphoric acid at 150 °C is
characterised by poor yields and difficulty in the isolation of pure
products from the crude reaction mixtures. Recognising the
biochemical utility of these heterocycles and the need for efficient
methods to generate various numbers of differently substituted
analogues, we sought out alternate synthetic methods.
The utility of palladium catalysed cross-coupling reactions has
evolved to become a major foundation by which new carbon–carbon
bonds are formed.11 The inclusion of microwave heating has aided
the speed and efficiency of these transformations, particularly in
the case of aryl–aryl Suzuki couplings.12–15 It was our goal to develop
a synthetic method for the formation of 3-substituted-2-aryl/het-
eroaryl imidazo[4,5-b]pyridines utilising a microwave-promoted
Suzuki coupling between substituted aryl/hetroaryl boronic acids
and a common 3-substituted-2-iodo-3H-imidazo[4,5-b]pyridine
derivative. A method for the construction of these derivatives using
this approach would allow for the rapid advancement of numerous
analogues via a final stage coupling from a common precursor. The
commercial availability of wide range of aryl/heteroaryl boronic
acids can be explored and by taking advantage of the broad
functional group tolerance of the Suzuki–Miyayura coupling, it
would be possible to efficiently prepare new analogues.
NH2
N
N
N
N
t-BuLi, -78° C
NIS
Formic acid
100° C
I
N
N
1
NH
R1
N
R1
R1
2
3
⇑
Corresponding author. at: School of chemical sciences, Nehru Arts and Science
College, Padnekad, Kanhangad, Kerala. Tel.: +91 95 487 2283466; fax: +91
04672280335.
R1= cyclohexyl (a), cyclopentyl (b)
E-mail addresses: sajithmeleveetil@gmail.com (A.M. Sajith), drmuralinasc@
yahoo.com (A. Muralidharan).
Scheme 1. Synthesis of 3-substituted-2-iodo-3H-imidazo[4,5-b]pyridine inter
mediate.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.12.051

A. M. Sajith, A. Muralidharan / Tetrahedron Letters 53 (2012) 1036–1041
1037
Table 1
Suzuki coupling of 3-substituted-2-iodo-3H-imidazo[4,5-b]pyridine (3a, 3b) and various boronic acids, 4a
Entry
Iodo intermediate, 3
ArB(OH)2, 4
Product, 5
Yieldb (%)
N
B(OH)2
N
I
O
O
N
N
N
N
N
O
1
95
4a
3a
5a
5b
B(OH)2
N
N
N
N
N
N
2
3
4
3a
85
93
91
O
4b
B(OH)2
N
N
N
N
3a
3a
5c
4c
B(OH)2
N
N
O
O
4d
S
5d
5e
N
N
B(OH)2
S
5
6
3a
3a
87
90
N
N
4e
B(OH)2
SO2Et
N
N
SO2Et
4f
5f
B(OH)2
F
N
N
7
3a
95
85
N
N
F
F
F
5g
4g
B(OH)2
N
N
O
N
N
8
9
3a
3a
5h
O
4h
B(OH)2
N
N
N
N
N
N
91
88
N
N
5i
4i
N
(HO)2B
N
N
N
N
N
N
N
5j
10
11
3a
3a
4j
88
(continued on next page)

1038
A. M. Sajith, A. Muralidharan / Tetrahedron Letters 53 (2012) 1036–1041
Table 1 (continued)
Entry
Iodo intermediate, 3
ArB(OH)2, 4
Product, 5
Yieldb (%)
(HO)2B
N
O
F
O
N
N
N
4k
5k
B(OH)2
N
N
N
12
13
14
15
16
3a
90
90
89
85
91
N
4l
F
5l
N
B(OH)2
CF3
I
N
N
N
N
N
N
F3C
CF3
3b
CF3
O
4m
5m
5n
(HO)2B
O
O
N
N
O
3b
4n
B(OH)2
F
N
N
CN
3b
3b
N
N
F
4o
5o
5p
CN
(HO)2B
O
OCF3
CF3
N
N
4p
N
(HO)2B
N
N
N
17
18
3b
96
N
N
4q
5q
5r
N
N
N
N
(HO)2B
3b
3b
90
90
4r
B(OH)2
Cl
Cl
N
N
19
N
4s
5s
a
Conditions: catalyst (A-taphos)2PdCl2 (5 mol %), 3-substituted-2-iodo-3H-imidazo[4,5-b]pyridine (3a, b) (0.1 mmol), boronic acid (0.18 mmol), CsF (0.2 mmol), DME/
MeOH (4:1), microwave irradiated at 150 W at 110 °C for 30 min.
b
Isolated yield.
Our method relies upon the facile synthesis of iodo intermedi-
ate 3a, 3b for the implementation of the final Suzuki reaction
(Scheme 1). The diamine derivatives (1a, 1b) were taken in formic
acid and refluxed overnight to yield compounds (2a, 2b). The iodo
intermediates were synthesised in excellent yield by treating com-
pounds (2a, 2b) in THF with t-butyl lithium at À78 °C for 30 min,
followed by the addition of N-iodo succinimide in anhydrous THF
dropwise at the same temperature and stirring was continued at
À78 °C for 1 h. The structure of the iodo compound was confirmed
by LC–MS, 1H NMR and 2D-NMR experiments. This key intermedi-

A. M. Sajith, A. Muralidharan / Tetrahedron Letters 53 (2012) 1036–1041
1039
Table 2
Effect of catalyst in Suzuki coupling of 3a with boronic acid 4ia
Entry
Catalyst
Base
Solvent
Yieldb (%)
Yieldb 2a (%)
1
2
3
4
5
6
7
8
9
Pd(PPh3)4
PdCl2(dppf)2
Pd2(dba)3
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(CH3CN)2
PdCl2(PPh3)2
PdCl2(PPh3)2
(A-taPhos)2PdCl2
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
CsF
CsF
CsF
CsF
DME–H2O (4:1)
DME–H2O (4:1)
DME–H2O (4:1)
DME–H2O (4:1)
DME–MeOH (4:1)
DME–MeOH (4:1)
DME–MeOH (4:1)
DMF
25
30
25
20
47
55
65
45
91
62
65
55
68
35
30
20
30
DME–MeOH (4:1)
Traces
a
Reaction conditions: 3a (0.1 mmol), 4i (0.18 mmol), Catalyst (5 mol %), Base (0.2 mmol), microwave irradiated at 110 W at 110 °C
for 30 min.
b
Isolated yield.
N
N
Table 3
Effect of base in Suzuki reaction of 3a with boronic acid, 4i
N
N
(A-taphos)2PdCl2
R2
I
R2B(OH)2
4
N
N
3
Yielda,b (%)
R1
Entry
Base
R1
CsF,DME/MeOH (4:1)
Microwave, 110° C
5
1
2
2
3
4
5
6
Na2CO3
NaHCO3
K2CO3
Cs2CO3
NaOH
K3PO4
CsF
31
35
25
40
Traces
65
91
5a-l (R1=Cyclohexyl)
R1= Cyclohexyl (a), Cyclopentyl (b)
R2= Aryl/ Heteroaryl
5m-s (R1=Cyclopentyl)
Scheme 2. Synthesis of 3-substituted-2-aryl/heteroaryl imidazo[4,5-b]pyridines.
a
Reaction conditions: 3a (0.1 mmol), 4i (0.18 mmol), (A-taphos)2PdCl2 (5 mol %),
Base (0.2 mmol), DME/MEOH (4:1), microwave irradiated at 110 W at 110 °C for
30 min.
b
Isolated yield.
N
ate was then subjected to Suzuki type reaction conditions {(A-ta-
phos)2PdCl2[5 mol %] in DME/MeOH [4:1], purged N2 for 10 min,
followed by 1.8 equiv of boronic acids (4a–s) and 2 equiv of CsF}.
The mixture was heated via microwave irradiation to 110 °C. Most
reactions achieved complete conversions within 30 min. The
resulting coupled products were purified by flash column chroma-
tography. Table 1 describes the scope and generality of the proce-
dure utilising variously substituted aryl/heteroaryl boronic acids to
yield numerous substituted 2-aryl/heteroaryl imidazo[4,5-b]pyri-
dine analogues. Yields were consistently greater than 85% for the
coupling procedure. The reaction tolerates both electron rich and
electron poor arylboronic acids.
P
N
Cl
Pd
P
Cl
(A-taphos)2PdCl2
Scheme 3. Structure of the key catalyst used in Suzuki.
In order to set the reaction parameters, a model system and a
range of conditions were explored for the optimisation of Suzuki
coupling of the iodo intermediate 3a and 2-dimethyl aminopyrimi-
dine 5-boronicacid 4i (Table 1, entry 9). A broad range of catalysts,
bases, solvent combinations and temperature ranges were tried on
this model system to get the coupled product in good yields (Tables
2 and 3). With most of these palladium catalysts, we observed the
deiodinated product 2a (Scheme 1) as a competing side product
along with the required product. Solvent combinations of DME/
H2O, DME/MeOH and DMF were tried on the model system. Table
2 shows that an effective catalytic species was obtained when
(A-taphos)2PdCl2 (Scheme 2) was used as the catalyst along with
CsF as the base in DME/MeOH combination under microwave en-
hanced conditions. Further investigations were made to explore
the effect of base on the Suzuki reaction of 3a (Scheme 1) with 4i
(Table 1, entry 9) keeping all the other conditions constant (Table
3). It was observed that 4i was obtained in exceptional yield when
CsF was used as the base.
decomposition of the iodo intermediate and an inability to recover
the coupled biaryl product.
The palladium catalysed dehalogenation of aromatic com-
pounds has been abundantly documented.16–18 Hydrodehalogen-
ation products have sometimes been observed as byproducts of
palladium catalysed cross-coupling reactions. In these cases, water
or tertiary amines have been assigned the role of hydride donors. In
Table 2, we describe a study of the effect of the catalyst in Suzuki
coupling of 3a with boronic acid 4i, where we observed the dehalo-
genated product along with the coupled product. The mechanism of
dehalogenation is believed to occur through the attack of metal alk-
oxides at the Pd(II) oxidative adduct complex formed by the oxida-
tive addition of aryl halide to Pd(0) catalyst.19,20 Subsequent
hydride migration and reductive elimination results in the side
product (reduced arene). While the attack of borate complex at
the same Pd(II) oxidative adduct complex leads to desired coupled
product. The relative rate difference between these two reactions
could, in principle, affect the final yield of coupled product. The
electronic effect of dimethylamino group (Scheme 3) increases
the basicity of phosphine ligand attached to the palladium centre
and that facilitates the coupling reaction21 resulting in improved
yield of the coupled product and reduces dehalogenation.
Various catalysts were explored as well as surveys of the inor-
ganic base, solvent combinations and temperature ranges. Better
conversions to products were obtained when CsF was used as the
base. Higher temperatures with shorter reaction times resulted in

1040
A. M. Sajith, A. Muralidharan / Tetrahedron Letters 53 (2012) 1036–1041
N
N
R1
I
N
N
R1
R2
N
Pd(0)L2
N
3
1
L
L
N
N
N
Pd R2
Pd
I
(II)
(II)
N
N
R1
N
L
R1
L
2
-
R2B(OH)2
(HO)2B
R2B(OH)2 + CsF
F
R1= Cyclohexyl, Cyclopentyl
R2= Aryl, Heteroaryl
F
Scheme 4. Mechanism of Suzuki coupling reaction.
2. (a) Chen, S. T.; Dost, G. (Merck) U.S. Pat. 5132,216, 1992.; (b) Roberts, D. A.;
Russel, S. T.; Ratcliffe, A. H.; Gibson, K.; Wood, R. (ICI). Eur. Pat., 399,731, 1990.
3. Weier, R. M.; Khanna, I. K.; Stealey, M. A.; Julien, J.(Searle). U.S. Pat., 5262,426,
1993.
4. Temple, C., Jr.; Rose, J. D.; Comber, R. N.; Rener, G. A. J. Med. Chem. 1987, 30,
1746.
5. Barraclough, P.; Black, J. W.; Cambridge, D.; Collard, D.; Firmin, D.;
Gerskowitch, V. P.; Glen, R. C.; Giles, H.; Hill, A. P.; Hull, R. A. D.; Iyer, R.;
King, W. R.; Kneen, C. O.; Lindon, J. C.; Nobbs, M. S.; Randall, P.; Shah, G. P.;
Smith, S.; Vine, S. J.; Whiting, M. V.; Williams, J. M. J. Med. Chem. 1990, 33, 2231.
6. Janssens, F.; Torremans, J.; Janssen, M.; Stokbroekx, R. A.; Luyckx, M.; Janseen,
P. A. J. J. Med. Chem. 1985, 28, 1943.
7. Bavetsias, V.; Sun, C.; Bouloc, N.; Reynisson, J.; Workman, P.; Linardopoulos, S.;
McDonald, E. Bioorg. Med. Chem. Lett. 2007, 17, 6567.
8. Kale, R. P.; Shaikh, M. U.; Jadhav, G. R.; Gill, C. H. Tetrahedron Lett. 2009, 50,
1780.
9. Mantlo, N. B.; Kim, D.; Ondeyka, D.; Chang, R. S. L.; Kivlighn, S. D.; Siegl, P. K. S.;
Greenlee, W. J. Biorg. Med. Chem. Lett. 1994, 4, 17.
10. Aridoss, G.; Balasubramanian, S.; Parthiban, P.; Kabilan, S. Eur. J. Med. Chem.
2006, 41, 268.
Similarly, for the same reason, the base which generates more reac-
tive borate species could facilitate transmetallation.22 In the
present study, CsF was found to lessen the dehalogenated side
product (Table 3) suggesting the formation of a highly reactive bor-
onate species, which is in agreement with earlier observations.21
The mechanism of Suzuki reaction involves an oxidative addition of
iodo intermediate with palladium to form the organo-palladium spe-
cies. Meanwhile boron atom of the boronic acid forms borate complex
with the base which enhances the polarisation of the organic ligand
thereby facilitating the transmetallation step. Finally reductive elimi-
nation takes place to give the coupled product (Scheme 4).
In conclusion, we have developed a concise, efficient and general
method for the synthesis of 3-substituted-2-aryl/heteroaryl imi-
dazo[4,5-b]pyridine analogues from a common precursor23,24. These
intermediates should find utility as synthons for the preparation of
medicinally relevant agents. The ready conversion of the iodo inter-
mediate to the boronate ester makes it a more versatile intermediate
to synthesise further more novel analogues. Work aimed at investi-
gating the further scope of the iodo intermediate is being pursued.
11. For some recent examples of Imidazo[4,5-b]pyridine synthesis see (a) Cundy,
D. J.; Holan, G.; Otaegui, M.; Simpson, G. W. Bioorg. Med. Chem. Lett. 1997, 7,
669; (b) Khanna, K. I.; Weier, R. M.; Lentz, K. T.; Swenton, L.; Lankin, D. C. J. Org.
Chem. 1995, 60, 960; (c) Grivas, S.; Lindström, S. J. Heterocyclic. Chem. 1995, 32,
467.
12. Suzuki, A. Chem. Commun. 2005, 4759.
13. Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250.
Acknowledgments
14. Montgomery, J. A.; Secrist, J. A. In Comprehensive Heterocyclic Chemistry;
Katritzky, R., Rees, C. W., Eds.; Vol. 5; Pergamon: Oxford, 1984. Section.
4.10.4.3.
15. Some recent reactions facilitated by microwave irradiations. Synthesis of
heterocycles: Triazoles: (a) Bentiss, F.; Lagrenee, M.; Barby, D. Tetrahedron Lett.
2000, 41, 1539; Thiazoquinazolines: (b) Besson, T.; Guil-lard, J.; Rees, C. W.
Tetrahedron Lett. 2000, 41, 1027; Quinolines: (c) Ranu, B. C.; Hajra, A.; Jana, U. C.
Tetrahedron Lett. 2000, 41, 5891.
The authors are thankful to the Organic Chemistry Division,
School of Chemical Science Department, Kannur University and
the Head of Chemistry Department, Govt. College Kasargod for pro-
viding facilities and good support for research work.
16. Ali, N. M.; McKillop, A.; Mitchell, M. B.; Rebello, R. A.; Wallbank, P. J.
Tetrahedron 1992, 48, 8117.
Supplementary data
17. Mahanty, J. S.; De, M.; Kundu, N. G. J. Chem. Soc., Perkin Trans. 1 1997, 2577.
18. (a) Hassan, J.; Penalva, V.; Lavenot, L.; Gozzi, C.; Lemaire, M. Tetrahedron 1998,
54, 13793; (b) Penalva, V.; Hassan, J.; Lavenot, L.; Gozzi, C.; Lemaire, M.
Tetrahedron Lett. 1998, 39, 2559.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.12.051.
19. Oscar Navarro, O.; Kaur, H.; Mahjoor, P.; Nolan, S. P. J. Org. Chem. 2004, 69,
3173.
20. Moon, J.; Lee, S. J. Organomet. Chem. 2004, 694, 473.
21. Guram, A. S.; Wang, X.; Bunel, E. E.; Faul, M. M.; Larsen, R. D.; Martinelli, M. J. J.
Org. Chem. 2007, 72, 5104.
References and notes
1. George, T.; Christopher, J. W.; George, W. W. J. Chem. Soc., Perkin Trans. 1 1999,
629.

A. M. Sajith, A. Muralidharan / Tetrahedron Letters 53 (2012) 1036–1041
1041
22. Slagt, V. F.; Vries, A. H. V.; Vries, J. G.; Kellogg, R. M. Org. Proc. Res. Dev. 2010, 14,
30.
24. Procedure for coupling of 3-cyclohexyl-2-(4-phenoxyphenyl)-3H-imidazo[4,5-
b]pyridine, 5a
23. Procedure for the preparation of 3-Cyclohexyl-2-iodo-3H-imidazo[4,5-b]pyridine,
3a
To a solution of 3-Cyclohexyl-2-iodo-3H-imidazo[4,5-b]pyridine derivative
(3a, 1 equiv) in dimethoxyethane/MeOH (4:1), was added (A-taphos)2PdCl2
(5 mol %). The solution was purged with nitrogen and stirred at room
temperature for 0.15 h, at which time 4-phenoxyphenyl boronic acid
(1.8 equiv), and cesium fluoride (2 equiv) were added. The reaction solution
was purged again with nitrogen and then placed in the microwave and heated
for 10–30 min at 110 °C. When TLC and LCMS showed full consumption of
starting materials, the reaction mixture was diluted with ethyl acetate,
separated the ethyl acetate layer, given water wash, brine wash and was
dried over anhydrous sodium sulphate and concentrated to get the crude
material. The crude product was directly purified by column chromatography
(0–20% hexane/EtOAc) to isolate the 3-cyclohexyl-2-(4-phenoxyphenyl)-3H-
imidazo[4,5-b]pyridine pyridine (5a, Scheme 2). Off white solid, Yield 95%, mp
(118.2–119.3 °C); 1H NMR (400 MHz, CDCl3) d: 1.27–1.39 (m, 4H), 1.74–1.97
(m, 4H), 2.81–2.85 (m, 2H), 4.38 (m, 1H), 7.11–7.23 (m, 6H), 7.38–7.44 (m, 2H),
7.62 (d, J = 9 Hz, 2H), 8.01 (d, J = 6 Hz, 1H), 8.37 (m, 1H); IR (KBr) 3052, 2934,
2853, 1586, 1488, 1255, 1243, 1230, 857, 775, 744 cmÀ1; LCMS 370.1 (M+H);
Anal. Calcd for C24H23N3O: C, 78.02; H, 6.27; N, 11.37. Found: C, 78.05; H, 6.30;
N, 11.38. Procedure for the synthesis of compounds 5b–5s is provided in
Supplementary data.
An oven dried flask was charged with imidazo[4,5-b]pyridine derivative, 2a
(1 equiv). Freshly distilled THF (5 volumes) was added to the reaction mixture.
The reaction mixture was cooled to À78 °C and t-butyllitium (1.7 M, 1.3 equiv)
in THF was added dropwise to the reaction mixture and stirring was continued
for 30 min at À78 °C. A solution of N-iodo succinimide (1.3 equiv) in THF
(5 volumes) was added dropwise over
a period of 20 min at the same
temperature. After the addition was complete the reaction mixture was
allowed to stir for 1 h at À78 °C. The reaction mixture was quenched with
saturated NH4Cl solution and extracted with ethyl acetate. The ethyl acetate
layer was then given water wash, brine wash, and dried over anhydrous
sodium sulphate, filtered and concentrated to get the crude mixture as brown
oil. The crude was purified by column chromatography using 60–120 mesh
silica (10%EtOAc in petroleum ether) to yield the iodo compound (3a,
Scheme 1). Yellow powder, Yield (89%), mp (110–112 °C); 1H NMR (400 MHz,
CDCl3): d 1.29–1.47 (m, 4H), 1.70–1.90 (m, 5H), 2.56–2.66 (m, 2H), 4.36–4.42
(m, 1H), 7.21–7.24 (m, 1H), 7.97–7.99 (m, 1H), 8.28–8.29 (m, 1H); IR (KBr)
2924, 2849, 1651, 1600, 1507, 1466, 1343, 1212, 745, 510 cmÀ1; LCMS 328.16
(M+H); Anal. Calcd for C12H14IN3: C, 44.05; H, 4.31; N, 12.84. Found: C, 44.23;
H, 4.40; N, 12.98. Procedure for the synthesis of compound 3b is provided in
Supplementary data.