The Journal of Organic Chemistry
NOTE
Dimethyl 6-Methoxy-4-methylquinoline-2,3-dicarboxylate,
3c: 124 mg, 40%; light brown solid; chromatographic eluent, petroleum
Hz, 2H), 3.26À3.32 (q, J = 7.60 Hz), 3.93 (s, 3H), 4.00 (s, 3H), 5.08 (s, 2H
+ bt, 1H), 7.27À7.33 (m, 5H), 7.60À7.62 (d, J= 8.40 Hz, 1H) 7.78 (s, 1H),
8.13À8.15 (d, J = 8.40 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 22.2, 27.0,
30.7, 40.6, 52.9, 53.3, 66.6, 122.8, 126.9, 127.1, 128.0, 128.1, 128.5, 131.0,
133.2, 136.5, 139.8, 144.1, 145.5, 146.3, 156.5, 165.7, 168.7; ESI-MS 451
[M + H]+. Anal. Calcd for C25H26N2O6: C, 66.65; H, 5.82; N, 6.22. Found:
C, 66.74; H, 5.77; N, 6.09.
General Procedure for the Preparation of Lactames 4hÀk.
Quinolines 3hÀk were treated with 2.5 equiv of potassium carbonate in
MeOH at 60 °C under magnetic stirring overnight. Afterward, the solvent
was removed under reduced pressure and the residue was washed with
chloroform to remove the organic impurities.
1
ether/AcOEt 1:1; mp 130À132 °C; H NMR (400 MHz, CDCl3) δ
2.64 (s, 3H), 3.96 (s, 3H), 3.99 (s, 3H), 4.01 (s, 3H), 7.21 (s, 1H),
7.42À7.45 (m, 1H), 8.14À8.16 (m, 1H); 13C NMR (100 MHz, CDCl3)
δ 15.8, 52.8, 53.3, 55.7, 101.9, 123.5, 128.0, 129.6, 132.7, 141.5, 142.1,
142.4, 160.0, 165.7, 168.8; ESI-MS 290 [M + H]+, 312 [M + Na]+. Anal.
Calcd for C15H15NO5: C, 62.28; H, 5.23; N, 4.84. Found: C, 62.09; H,
5.19; N, 4.97.
Dimethyl 6-Fluoro-4-methylquinoline-2,3-dicarboxylate,
3d: 169 mg, 61%; light brown solid; chromatographic eluent, petroleum
ether/AcOEt 1:1; mp 93À95 °C; 1H NMR (200 MHz, CDCl3) δ 2.66
(s, 3H), 3.99 (s, 3H), 4.02 (s, 3H), 7.53À7.69 (m, 2H), 8.22À8.29 (m,
1H); 13C NMR (100 MHz, CDCl3) δ 15.7, 53.0, 53.5, 108.2, 121.0,
121.5, 127.9, 129.4, 133.7, 133.9, 143.4, 159.6, 165.4, 168.2; ESI-MS 278
[M + H]+, 300 [M + Na]+. Anal. Calcd for C14H12FNO4: C, 60.65; H,
4.36; N, 5.05. Found: C, 60.78; H, 4.19; N, 5.09.
Potassium 4-Oxo-1,2,3,4-tetrahydrobenzo[c][2,7]naphthy-
ridine-5-carboxylate, 4g: 80 mg, 70%; pale brown solid; mp
1
>300 °C; H NMR (200 MHz, D2O) δ 3.40À3.47 (t, J = 7.00 Hz,
2H), 3.61À3.68 (t, J = 7.00 Hz, 2H), 7.31 (br s, 1H), 7.61À8.19 (m,
4H); 13C NMR (50 MHz, D2O) δ 24.7, 39.1, 125.4, 126.5, 128.4, 128.8,
129.2, 129.6, 130.3, 137.2, 149.8, 158.8, 171.6; ESI-MS 241 [M-K]À.
HRMS (ESI) calcd for C13H9N2O3K2+ 318.9887, found 318.9883.
Potassium 9-Methyl-4-oxo-1,2,3,4-tetrahydrobenzo[c][2,7]
naphthyridine-5-carboxylate, 4h: 129 mg, 81%; orange solid; mp
>300 °C; 1H NMR (200 MHz, CD3OD) δ 2.58 (s, 3H), 3.37À3.43 (t, J =
6.80 Hz, 2H), 3.59À3.66 (t, J = 6.80 Hz, 2H), 7.32 (br s, 1H), 7.65À7.96
(m, 3H); 13C NMR (50 MHz, D2O) δ 24.3, 24.8, 39.0, 119.1, 123.6,
126.3, 126.5, 129.2, 129.7, 131.3, 132.2, 144.5, 166.2, 172.0; ESI-MS 333
Dimethyl 4-(2-(Benzyloxycarbonylamino)ethyl)quinoline-
2,3-dicarboxylate, 3g: 160 mg, 36%; yellow oil; chromatographic
1
eluent, petroleum ether/AcOEt 3:2; H NMR (200 MHz, CDCl3) δ
3.32À3.39 (t, J = 6.61 Hz, 2H), 3.51À3.58 (q, J = 6.61 Hz, 2H), 3.96 (s,
3H), 4.02 (s, 3H), 5.09 (s, 2H), 5.30 (bt, J = 6.61 Hz, 1H), 6.82À6.86
(m, 1H), 7.31 (m, 5H), 7.70À7.81 (m, 2H), 8.24À8.34 (m, 1H); 13C
NMR (50 MHz, CDCl3) δ 30.2, 41.4, 53.1, 53.4, 66.7, 119.0, 124.3,
128.1, 128.5, 129.5, 129.7, 131.2, 131.2, 136.3, 136.4, 144.5, 146.9, 156.4,
156.5, 165.6, 168.4; ESI-MS 423 [M + H]+, 445 [M + Na]+. Anal. Calcd
for C23H22N2O6: C, 65.39; H, 5.25; N, 6.63. Found: C, 65.46; H, 5.19;
N, 6.77.
Dimethyl 4-(2-(Benzyloxycarbonylamino)ethyl)-6-methyl-
quinoline-2,3-dicarboxylate, 3h: 209 mg, 48%; yellow oil; chro-
matographic eluent, petroleum ether/AcOEt 3:2; 1H NMR (200 MHz,
CDCl3) δ 2.59 (s, 3H), 3.28À3.36 (t, J = 6.94 Hz, 2H), 3.52À3.61 (q, J =
6.94 Hz, 2H), 3.97 (s, 3H), 4.02 (s, 3H), 5.09 (s, 2H), 5.29 (bt, J = 6.94
Hz, 1H), 7.31 (s, 5H), 7.62À7.67 (d, J = 8.54 Hz, 1H), 8.04 (s, 1H),
8.14À8.18 (d, J = 8.54 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 22.3,
30.1, 41.3, 53.1, 53.4, 66.6, 123.1, 127.5, 128.0, 128.1, 128.5, 130.9, 133.5,
136.3, 140.2, 143.6, 144.0, 145.4, 156.5, 165.6, 168.6; ESI-MS 437 [M +
H]+. Anal. Calcd for C24H24N2O6: C, 66.04; H, 5.54; N, 6.42. Found: C,
65.90; H, 5.61; N, 6.38.
Dimethyl 4-(2-(Benzyloxycarbonylamino)ethyl)-6-methoxy-
quinoline-2,3-dicarboxylate, 3i: 172 mg, 38%; brown oil; chro-
matographic eluent, petroleum ether/AcOEt 1:1; 1H NMR (200 MHz,
CDCl3) δ 3.23À3.29 (t, J = 6.90 Hz, 2H), 3.48À3.58(q, J = 6.90 Hz,
2H), 3.96 (s, 3H), 4.01 (s, 3H), 4.04 (s, 3H), 5.09 (s, 2H), 5.26 (bt, J =
6.90 Hz, 1H), 7.36 (m, 5H), 7.44 (m, 1H), 7.71 (m, 1H), 8.15 (m, 1H);
13C NMR (50 MHz, CDCl3) δ 30.7, 40.9, 52.1, 53.0, 53.3, 56.0, 66.6,
102.1, 124.2, 127.9, 128.0, 128.1, 128.5, 129.2, 132.6, 136.3, 142.0, 142.9,
156.6, 160.4, 165.6, 168.8; ESI-MS 453 [M + H]+, 475 [M + Na]+. Anal.
Calcd for C24H24N2O7: C, 63.71; H, 5.35; N, 6.19. Found: C, 63.64; H,
5.48; N, 6.26.
+
[M + K]+, 255 [M À K]À; HRMS (ESI) calcd for C14H11N2O3K2
333.0044, found 333.0038.
Potassium 9-Methoxy-4-oxo-1,2,3,4-tetrahydrobenzo[c]-
[2,7]naphthyridine-5-carboxylate, 4i: 110 mg, 83%; yellow solid;
mp >300 °C; 1H NMR (200 MHz, CD3OD) δ 3.33À3.39 (t, J = 6.10 Hz,
2H), 3.60À3.66 (t, J = 6.10 Hz, 2H), 3.96 (s, 3H), 7.38À7.95 (m, 3H); 13C
NMR (50 MHz, D2O) δ 24.7, 39.0, 56.5, 103.8, 115.9, 118.7, 124.9, 126.4,
130.2, 143.2, 149.9, 158.5, 166.5, 176.5; ESI-MS 349 [M + K]+, 271 [M À
K]À; HRMS (ESI) calcd for C14H11N2O4K2+ 348.9993, found 348.9989.
Potassium 9-Fluoro-4-oxo-1,2,3,4-tetrahydrobenzo[c][2,7]
naphthyridine-5-carboxylate, 4j: 105 mg, 74%; pale brown solid;
mp >300 °C; 1H NMR (200 MHz, CD3OD) δ 3.28À3.35 (t, J = 6.90
Hz, 2H), 3.60À3.67 (t, J = 6.90 Hz, 2H), 7.28 (br s, 1H), 7.68À8.12 (m,
3H); 13C NMR (50 MHz, D2O) δ 21.7, 39.1, 118.4, 124.5, 125.3, 128.4,
135.4, 139.2, 145.9, 150.9, 156.5, 166.6, 176.7; ESI-MS 299 [M + H]+;
HRMS (ESI) calcd for C13H8FN2O3K2+ 336.9793, found 336.9788.
’ ASSOCIATED CONTENT
S
Supporting Information. NMR spectra of new com-
b
pounds. This material is available free of charge via the Internet at
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: ponticelli@unisi.it.
Dimethyl 4-(2-(Benzyloxycarbonylamino)ethyl)-6-fluoro-
quinoline-2,3-dicarboxylate, 3j: 185 mg, 42%; orange oil; chro-
matographic eluent, petroleum ether/AcOEt 1:1; H NMR (200 MHz,
1
CDCl3) δ 3.26À3.33 (t, J = 6.69 Hz, 2H), 3.49À3.59 (q, J = 6.69 Hz, 2H),
3.97 (s, 3H), 4.03 (s, 3H), 5.10 (s, 2H), 5.24 (bt, J = 6.69 Hz, 1H),
7.31À7.33 (m, 5H), 7.59 (m, 1H), 7.97 (m, 1H), 8.28 (m, 1H); 13C NMR
(50 MHz, CDCl3) δ 29.7, 41.0, 53.2, 53.5, 66.8, 66.9, 108.0, 108.5,
121.4, 122.0, 128.0, 128.1, 128.5, 133.8, 134.0, 136.3, 144.0, 156.5, 159.9,
165.4, 168.2; ESI-MS 441 [M + H]+, 463 [M + Na]+. Anal. Calcd for
C23H21FN2O6: C, 62.72; H, 4.81; N, 6.36. Found: C, 62.58; H, 4.87; N, 6.22.
Dimethyl 4-(3-(Benzyloxycarbonylamino)propyl)-6-methyl-
quinoline-2,3-dicarboxylate, 3k: 158 mg, 35%; yellow oil; chromato-
graphic eluent, petroleum ether/AcOEt 1:1; 1H NMR (400 MHz, CDCl3)
δ 1.90À1.98 (quintet, J = 7.60 Hz, 2H), 2.56 (s, 3H), 3.05À3.09 (t, J = 7.60
’ ACKNOWLEDGMENT
The work was financially supported by the PRIN Project 2009.
The authors wish to thank Dr. Sara Draghi and Centro di Analisi e
Determinazioni Strutturali of the University of Siena for recording
MS spectra.
’ REFERENCES
(1) (a) Bose, D. S.; Idrees, M.; Jakka, N. M.; Rao, J. V. J. Comb. Chem.
2010, 12, 100–110. (b) Larsen, R. D.; Corley, E. G.; King, A. O.; Carrol,
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dx.doi.org/10.1021/jo201316k |J. Org. Chem. 2011, 76, 7597–7601