2676
K. Kobayashi et al.
PAPER
Rohrer, S. P.; Schaeffer, J. M.; Rohdes, L.; Drisko, J. E.;
3-(1-Acetylamino-1-phenylmethyl)-1,6-dimethylquinolin-
2(1H)-one (4e)
McGowan, E.; Macintyre, D. E.; Vincent, S.; Carlin, J. R.;
Cameron, J.; Smith, R. G. J. Med. Chem. 2001, 44, 917.
(b) Hewawasam, P.; Fan, W.; Knipe, J.; Moon, S. L.;
Boissard, C. G.; Gribkoff, V. K.; Starrett, J. E. Jr.; Lodge, N.
J. Bioorg. Med. Chem. Lett. 2002, 12, 1779. (c) Angibaud,
P.; Bourdrez, X.; Devine, A.; End, D. W.; Freyne, E.; Lingy,
Y.; Muller, P.; Mannens, G.; Pilatte, I.; Poncelet, V.; Skrzat,
S.; Smets, G.; Dun, J. V.; Remoortere, P. V.; Venet, M.;
Wouters, W. Bioorg. Med. Chem. Lett. 2003, 13, 1543.
(d) Hewawasam, P.; Fan, W.; Ding, M.; Cook, D.; Goggins,
G. D.; Mters, R. A.; Gribkoff, V. K.; Boissard, C. G.;
Dworetzky, S. I.; Starrett, J. E. Jr.; Lodge, N. J. J. Med.
Chem. 2003, 46, 2819. (e) Jiang, J.; DeVita, R. J.; Goulet,
M. T.; Wyvratt, M. J.; Lo, J.-L.; Ren, N.; Yudkovitz, J. B.;
Cui, J.; Yang, Y. T.; Cheng, K.; Rohrer, S. P. Bioorg. Med.
Chem. Lett. 2004, 14, 1795. (f) Marcaccini, S.; Pepino, R.;
Pozo, M. C.; Basurto, S.; García-Valverde, M.; Torroba, T.
Tetrahedron Lett. 2004, 45, 3999. (g) Hewawasam, P.; Fan,
W.; Cook, D. A.; Newberry, K. S.; Boissard, C. G.; Gribkoff,
V. K.; Starrett, J. E. Jr.; Lodge, N. J. Bioorg. Med. Chem.
Lett. 2004, 14, 4479. (h) DeVita, R. J.; Parikh, M.; Jiang, J.;
Fair, J. A.; Young, J. R.; Walsh, T. F.; Goulet, M. T.; Lo, J.-
L.; Ren, N.; Yudkovitz, J. B.; Cui, J.; Yang, Y. T.; Cheng,
K.; Rohrer, S. P.; Wyvratt, M. J. Bioorg. Med. Chem. Lett.
2004, 14, 5599; and references cited therein.
Yield: 83%; white solid; mp 156–158 °C (hexane–CH2Cl2).
IR (KBr): 3304, 1651 cm–1.
1H NMR: d = 2.09 (3 H, s), 2.44 (3 H, s), 3.68 (3 H, s), 6.27 (1 H, d,
J = 9.2 Hz), 7.21 (1 H, t, J = 7.3 Hz), 7.25–7.30 (3 H, m), 7.35–7.42
(4 H, m), 7.80 (1 H, s), 7.84 (1 H, br d, J = 9.2 Hz).
MS: m/z (%) = 277 (56, [(M – Ac)+]), 248 (100).
Anal. Calcd for C20H20N2O2: C, 74.98; H, 6.29; N, 8.74. Found: C,
74.88; H, 6.48; N, 8.84.
3-(1-Acetylamino-1-phenylmethyl)-6-chloro-1-methylquinolin-
2(1H)-one (4f)
Yield: 82%; pale-yellow solid; mp 226–227 °C (hexane–CH2Cl2).
IR (KBr): 3296, 1653, 1628 cm–1.
1H NMR: d = 2.09 (3 H, s), 3.67 (3 H, s), 6.28 (1 H, d, J = 9.2 Hz),
7.21–7.32 (4 H, m), 7.35 (2 H, d, J = 7.8 Hz), 7.52 (1 H, dd, J = 8.7,
2.3 Hz), 7.60 (1 H, d, J = 2.3 Hz), 7.64 (1 H, br d, J = 9.2 Hz), 7.77
(1 H, s).
MS: m/z (%) = 340 (2.5, [M+]), 297 (100).
Anal. Calcd for C19H17ClN2O2: C, 66.96; H, 5.03; N, 8.22. Found:
C, 67.00; H, 5.05; N, 8.13.
(2) See, e.g.: (a) Asherson, J. L.; Young, D. W. J. Chem. Soc.,
Chem. Commun. 1977, 916. (b) Jha, I. S.; Kanth, A. K.;
Singh, L. Orient. J. Chem. 1998, 14, 489; Chem. Abstr.
1999, 130, 281972h.
(3) (a) Hiyama, T.; Kobayashi, K. Tetrahedron Lett. 1982, 23,
1597. (b) Kobayashi, K.; Suginome, H. Bull. Chem. Soc.
Jpn. 1986, 59, 2635. (c) Hiyama, T.; Kobayashi, K.;
Nishide, K. Bull. Chem. Soc. Jpn. 1987, 60, 2127.
3-[1-Acetylamino-1-(pyridin-2-yl)methyl]-6-chloro-1-methyl-
quinolin-2(1H)-one (4g)
6-Chloro-1-methyl-3,4-dihydroquinolin-2(1H)-one (1c; 0.19 g,
0.96 mmol) was allowed to react with pyridine-2-carbonitrile (0.10
g, 0.98 mmol) and worked up in a manner similar to that described
for the reaction of 1-methyl-3,4-dihydroquinolin-2(1H)-one (1a)
with benzonitrile. The crude mixture was treated with Ac2O–pyri-
dine at 60 °C as described for the preparation of 3a. Purification of
the reaction mixture by preparative TLC on SiO2 (hexane–THF,
2:3) gave directly 4g; pale-yellow solid; yield: 0.21 g (65%); mp
202–205 °C (hexane–CH2Cl2).
(d) Kobayashi, K.; Kanno, Y.; Seko, S.; Suginome, H. J.
Chem. Soc., Chem. Commun. 1992, 780.
(4) Kobayashi, K.; Kitamura, T.; Nakahashi, R.; Shimizu, A.;
Morikawa, O.; Konishi, H. Heterocycles 2000, 53, 1021.
(5) For other recent reports from our laboratory on the
heterocycle synthesis utilizing magnesium enolates, see:
(a) Kobayashi, K.; Takabatake, H.; Kitamura, T.; Morikawa,
O.; Konishi, H. Bull. Chem. Soc. Jpn. 1997, 70, 1697.
(b) Kobayashi, K.; Nakahashi, R.; Shimizu, A.; Kitamura,
T.; Morikawa, O.; Konishi, H. J. Chem. Soc., Perkin Trans.
1 1999, 1747. (c) Kobayashi, K.; Matoba, T.; Irisawa, S.;
Takanohashi, A.; Tanmatsu, M.; Morikawa, O.; Konishi, H.
Bull. Chem. Soc. Jpn. 2000, 73, 2805. (d) Kobayashi, K.;
Nakashima, T.; Mano, M.; Morikawa, O.; Konishi, H. Chem.
Lett. 2001, 602. (e) Kobayashi, K.; Nakahashi, R.; Mano,
M.; Morikawa, O.; Konishi, H. Bull. Chem. Soc. Jpn. 2003,
76, 1257. (f) Kobayashi, K.; Honma, K.; Kondo, S.;
Morikawa, O.; Konishi, H. Heterocycles 2005, 65, 619; and
references cited therein.
IR (KBr): 3352, 1643, 1622 cm–1.
1H NMR: d = 2.13 (3 H, s), 3.65 (3 H, s), 6.36 (1 H, d, J = 7.8 Hz),
7.16 (1 H, ddd, J = 7.3, 4.1, 0.9 Hz), 7.25 (1 H, d, J = 8.7 Hz), 7.48
(1 H, dd, J = 8.7, 2.3 Hz), 7.58–7.61 (2 H, m), 7.65 (1 H, td, J = 7.8,
1.8 Hz), 7.70 (1 H, br d, J = 7.8 Hz), 7.82 (1 H, s), 8.49 (1 H, d,
J = 4.1 Hz).
MS: m/z (%) = 341 (12, [M+]), 298 (100).
Anal. Calcd for C18H16ClN3O2: C, 63.25; H, 4.72; N, 12.29. Found:
C, 62.96; H, 4.70; N, 12.18.
Acknowledgment
This work was partially supported by a Grant-in-Aid for Scientific
Research (C) 15550092 from Japan Society for the Promotion of
Science.
(6) 2,3-Dihydroquinolin-2(1H)-one was commercially
available and the others were prepared by the procedure
reported in the following paper: Guaruna, A.; Machetti, F.;
Occhiato, E. G.; Scarpi, D. J. Med. Chem. 2000, 43, 3718.
(7) Morfat, A.; Carta, M. Synthesis 1987, 515.
References
(1) (a) DeVita, R. J.; Walsh, T. F.; Young, J. R.; Jiang, J.;
Ujjainwalla, F.; Toupence, R. B.; Parikh, M.; Huang, S. X.;
Fair, J. A.; Goulet, M. T.; Wyvratt, M. J.; Lo, J.-L.; Ren, N.;
Yudkovitz, J. B.; Yang, Y. T.; Cheng, K.; Cui, J.; Mount, G.;
(8) Venkov, A. P.; Statkova-Abeghe, S. M. Tetrahedron 1996,
52, 1451.
Synthesis 2005, No. 16, 2673–2676 © Thieme Stuttgart · New York