PAPER
Derivatization of N-Heteroaromatic Cations
3013
1,3-Bis(4-methoxyphenyl)-12,13-dihydro-5H-13-aza-4a-azonia-
benzo[4,5]cyclohepta[1,2-b]naphthalene Bromide (5g)
Yield: 85%; brown solid; mp 246–248 °C; Rf 0.24 (MeOH–EtOAc,
30%).
1H NMR (600 MHz, DMSO-d6): d = 3.79 (s, 3 H), 3.82 (s, 3 H),
5.02 (m, 2 H), 6.05 (m, 2 H), 7.04 (m, 2 H), 7.07 (m, 2 H), 7.39 (m,
2 H), 7.58 (m, 2 H), 7.66 (m, 2 H), 7.74 (s, 1 H), 7.89 (s, 1 H), 7.97
(m, 2 H), 8.20 (s, 1 H), 8.50 (s, 1 H).
1H NMR (600 MHz, DMSO-d6): d = 2.10 (m, 2 H), 3.38 (m, 2 H),
4.27 (m, 2 H), 6.99 (m, 1 H), 7.31 (m, 2 H), 7.60 (m, 2 H), 7.95 (s,
1 H), 8.32 (m, 1 H).
13C NMR (150 MHz, DMSO-d6): d = 17.6 (CH2), 38.2 (CH2), 50.4
(CH2), 83.6 (C), 90.0 (C), 106.3 (C), 115.1 (CH), 116.2 (CH), 116.4
(CH), 118.0 (C), 133.6 (CH), 141.9 (CH), 142.6 (CH), 150.7 (C),
161.5 (C), 162.4 (CH).
HRMS (ESI): m/z [M – Br]+ calcd for C16H14FN2: 253.1136; found:
253.1157.
HRMS (ESI): m/z [M – Br]+ calcd for C31H27N2O2: 459.2067;
found: 459.2091.
8-Phenylethynyl-2,3,4,5-tetrahydro-1H-pyrido[1,2-a][1,3]di-
azepin-6-ylium Bromide (7c)
Yield: 77%; brown oil; Rf 0.14 (MeOH–EtOAc, 30%).
3-Naphthalen-2-yl-5,6,7,8,9,10-hexahydro-10-aza-4a-azonia-
benzocyclooctene Bromide (5h)
Yield: 80%; brown solid; mp 216–218 °C; Rf 0.15 (MeOH–EtOAc,
30%).
1H NMR (300 MHz, DMSO-d6): d = 1.54 (m, 2 H), 1.89 (m, 2 H),
2.16 (m, 2 H), 3.87 (m, 2 H), 4.76 (m, 2 H), 7.17 (m, 1 H), 7.55 (m,
2 H), 7.92 (m, 3 H), 8.06 (m, 1 H), 8.23 (m, 1 H), 8.37 (s, 1 H), 8.44
(s, 1 H), 9.12 (br s, 1 H).
1H NMR (600 MHz, DMSO-d6): d = 1.85 (m, 2 H), 1.98 (m, 2 H),
3.62 (m, 2 H), 4.00 (m, 2 H), 7.10 (m, 1 H), 7.36 (m, 1 H), 7.45 (m,
3 H), 7.53 (m, 1 H), 7.68 (m, 1 H), 8.32 (m, 1 H), 9.15 (br s, 1 H).
HRMS (ESI): m/z [M – Br]+ calcd for C17H17N2: 249.1386; found:
249.1397.
13C NMR (150 MHz, DMSO-d6): d = 19.1 (CH2), 28.3 (CH2), 29.7
(CH2), 42.7 (CH2), 54.9 (CH2), 117.6 (CH), 123.8 (CH), 124.7
(CH), 125.1 (C), 125.8 (CH), 126.4 (CH), 126.6 (CH), 127.5 (CH),
128.3 (CH), 131.3 (C), 132.4 (C), 133.1 (C), 138.7 (CH), 139.2
(CH), 154.8 (C).
8-(4-Fluorophenylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[1,2-
a][1,3]diazepin-6-ylium Bromide (7d)
Yield: 71%; brown oil; Rf 0.15 (MeOH–EtOAc, 30%).
1H NMR (600 MHz, DMSO-d6): d = 3.07 (m, 2 H), 3.22 (m, 2 H),
3.43 (m, 2 H), 4.16 (m, 2 H), 7.02 (m, 1 H), 7.29 (m, 1 H), 7.60 (m,
1 H), 7.76 (m, 2 H), 7.88 (m, 1 H), 8.45 (m, 1 H), 8.95 (br s, 1 H).
HRMS (ESI): m/z [M – Br]+ calcd for C20H21N2: 289.1699; found:
289.1682.
HRMS (ESI): m/z [M – Br]+ calcd for C17H16FN2: 267.1292; found:
267.1273.
Synthesis of Aryl Alkynylated Pyrido-Fused Tetrahydropyrim-
idinums and Diazepaniums; General Procedure
Aryl acetylene 6a or 6b (3 mmol) was taken in a 25 mL round-bot-
tomed flask and anhydrous DMF (5 mL) was added, followed by
CuI (3 mmol) and Na2CO3 (3 mmol). The solution was then de-
gassed and back-filled with nitrogen (4–5 times) and stirred at r.t.
for 10 min (generation of a yellow color). Pyridinium cation 3a or
3c (3 mmol), Pd(OAc)2 (0.1 mmol), and Ph3P (0.2 mmol) were add-
ed to the reaction mixture and the solution was degassed and back-
filled with nitrogen (4–5 times). The flask was then fitted with a
septum and the mixture was subjected to irradiation in a microwave
reactor (CEM, Discover, USA) at 80 °C (180 W) for the appropriate
amount of time (reaction monitored by TLC). After completion of
the reaction, the reaction mixture was cooled, diluted with MeOH,
and vacuum-filtered through a sintered glass funnel. The filtrate
was then evaporated to dryness in a rotary evaporator under reduced
pressure and the residue was purified by chromatography over neu-
tral alumina, eluting with a mixture of EtOAc–MeOH.
Acknowledgment
We thank the Council of Scientific and Industrial Research (CSIR),
New Delhi, for financial support in the form of fellowships (R.P.,
S.M., A.M., S.N., A.H., K.B.S., and P.S.). We are also thankful to
Dr. B. Achari, Emeritus Scientist, CSIR, for useful suggestions and
encouragement. Special thanks are due to Professor B. C. Ranu of
IACS, Kolkata, for his generous cooperation in utilizing the MW in-
strument.
References
(1) Brana, M. F.; Cacho, M.; Gradillas, A.; de Pascual-Teresa,
B.; Ramos, A. Curr. Pharm. Des. 2001, 7, 1745.
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13, 2017.
7-Phenylethynyl-1,2,3,4-tetrahydropyrido[1,2-a]pyrimidin-5-
ylium Bromide (7a)
Yield: 76%; brown oil; Rf 0.15 (MeOH–EtOAc, 30%).
1H NMR (600 MHz, DMSO-d6): d = 2.10 (m, 2 H), 3.56 (m, 2 H),
4.26 (m, 2 H), 7.04 (m, 1 H), 7.45 (m, 3 H), 7.53 (m, 2 H), 7.82 (m,
1 H), 8.30 (m, 1 H).
(5) (a) García, D.; Cuadro, A. M.; Alvarez-Builla, J.; Vaquero,
J. J. Org. Lett. 2004, 6, 4175. (b)Lambert, C.; Gaschler, W.;
Nöll, G.; Weber, M.; Schmälzlin, E.; Bräuchle, C.;
Meerholz, K. J. Chem. Soc., Perkin Trans. 2 2001, 964.
(c) Barchín, B. M.; Valenciano, J.; Cuadro, A. M.; Alvarez-
Builla, J.; Vaquero, J. J. Org. Lett. 1999, 1, 545. (d) Reyes,
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2004, 45, 8713. (e) Córdoba, M.; Izquierdo, M. L.; Alvarez-
Builla, J. Tetrahedron Lett. 2011, 52, 1738.
13C NMR (150 MHz, DMSO-d6): d = 17.7 (CH2), 38.3 (CH2), 50.5
(CH2), 83.9 (C), 91.1 (C), 106.4 (C), 115.2 (CH), 121.6 (C), 129.0
(2 × CH), 129.4 (CH), 131.4 (2 × CH), 141.9 (CH), 142.5 (CH),
150.7 (C).
HRMS (ESI): m/z [M – Br]+ calcd for C16H15N2: 235.1230; found:
235.1219.
7-(4-Fluorophenylethynyl)-1,2,3,4-tetrahydropyrido[1,2-a]py-
rimidin-5-ylium Bromide (7b)
Yield: 74%; brown oil; Rf 0.16 (MeOH–EtOAc, 30%).
(6) (a) Bringmann, G.; Gunther, C.; Ochse, M.; Schupp, O.;
Tasler, S. In Progress in the Chemistry of Organic Natural
Synthesis 2011, No. 18, 3006–3014 © Thieme Stuttgart · New York