B. S. Lee et al. / Bioorg. Med. Chem. 11 (2003) 4949–4958
4953
3-Ethyl-3,4-dihydro-2(1H)-quinolinone (3b). 61%, white
solid, mp 79–81 ꢀC; 1H NMR (CDCl3) d 9.09 (br s, 1H),
7.12–7.19 (m, 2H), 6.92–7.00 (m, 1H), 6.82 (d, J=7.8
Hz, 1H), 3.04 (dd, J=15.8, 6.0Hz, 1H), 2.75 (dd,
J=15.6, 8.6 Hz, 1H), 2.40–2.55 (m, 1H), 1.79–1.99 (m,
1H), 1.40–1.62 (m, 1H), 1.02 (t, J=7.3 Hz, 3H); 13C
NMR (CDCl3) d 172.2, 135.4, 126.5, 125.7, 121.6, 121.2,
113.4, 39.9, 28.5, 21.0, 9.8; MS (EI) m/z 175 (M+), 146
(100), 132, 118, 106. Anal. calcd for C11H13NO: C,
75.39; H, 7.48; N, 8.00. Found: C, 75.15; H, 7.80; N,
8.31.
3-Methyl-6-nitro-3,4-dihydro-2(1H)-quinolinone (4a).
Mp 213–214 ꢀC; H NMR (CDCl3) d 8.92 (br s, 1H),
1
8.09–8.12 (m, 2H), 6.90 (d, J=9.0Hz, 1H), 3.12 (dd,
J=15.0, 5.2 Hz, 1H), 2.66–2.90 (m, 2H), 1.32 (d, J=6.6
Hz, 3H); 13C NMR (DMSO-d6) d 170.1, 122.0, 121.0,
120.9, 112.3, 112.3, 95.5, 31.6, 30.2 12.0; MS (EI) m/z
206 (M+, 100), 178, 131, 117. Anal. calcd for
C10H10N2O3: C, 58.24; H, 4.89; N, 13.59. Found: C,
58.46; H, 4.70; N, 13.91.
3 - Ethyl - 6 - nitro - 3,4 - dihydro - 2(1H) - quinolinone (4b).
50%, white solid, mp 191–192 ꢀC; H NMR (CDCl3) d
1
3-Propyl-3,4-dihydro-2(1H)-quinolinone (3c). 44%, white
9.35 (br s, 1H), 8.10(br s, 2H), 6.91 (d, J=9.2 Hz, 1H),
3.14 (dd, J=16.2, 6.2 Hz, 1H0, 2.86 (dd, J=16.2, 9.0Hz,
1H), 2.47–2.61 (m, 1H), 1.83–1.96 (m, 1H), 1.43–1.65 (m,
1H), 1.04 (t, J=7.5 Hz, 3H); 13C NMR (DMSO-d6) d
171.4, 143.3, 140.6, 123.2, 122.6, 113.8, 39.4, 28.0, 21.2,
10.1; MS (EI) m/z 220( M +) 191 (100), 177, 145, 130,
117. Anal. calcd for C11H12N2O3: C, 59.99; H, 5.49; N,
12.72. Found: C, 60.03; H, 5.58; N, 12.49.
solid, mp 105–107 ꢀC; H NMR (CDCl3) d 8.74 (br s,
1
1H), 7.12–7.20(m, 2H), 6.96 (td, J=7.2, 1.3 Hz, 1H),
6.80(d, J=7.6 Hz, 1H), 3.11 (dd, J=15.6, 3.0Hz, 1H),
2.73 (dd, J=15.8, 8.5 Hz, 1H), 2.52–2.59 (m, 1H),
1.74–1.88 (m, 1H), 1.37–1.58 (m, 3H), 0.93 (t, J=7.0
Hz, 3H); 13C NMR (CDCl3) d 172.6, 135.4, 126.5,
125.7, 121.6, 121.2, 113.3, 38.2, 30.0, 29.0, 18.5, 12.3;
MS (EI) m/z 191 (M+, 100), 161, 145, 130, 117. Anal.
calcd for C12H15NO: C, 76.15; H, 7.99; N, 7.40. Found:
C, 76.05; H, 8.12; N, 7.41.
3-Propyl-6-nitro-3,4-dihydroꢀ-2(1H)-quinolinone (4c).
1
84%, white solid, mp 207–208 C; H NMR (CDCl3) d
9.07 (br s, 1H), 8.08–8.11 (m, 2H), 6.89 (d, J=0.2 Hz,
1H), 3.15 (dd, J=16.2, 5.8 Hz, 1H), 2.84 (dd, J=16.1,
8.5 Hz, 1H), 2.59–2.66 (m, 1H), 1.79–1.85 (m, 1H),
1.39–1.55 (m, 3H), 0.95 (t, J=6.8 Hz, 3H); 13C NMR
(DMSO-d6) d 172.3, 141.5, 141.0, 122.5, 122.2, 122.2,
113.3, 37.6, 30.0, 28.7, 18.4, 12.2; MS (EI) m/z 234
(M+), 191 (100), 161, 145, 130, 117. Anal. calcd for
C12H14N2O3: C, 61.53; H, 6.02; N, 11.96. Found: C,
61.05; H, 6.17; N, 11.92.
3-(3-Chloropropyl)-3,4-dihydro-2(1H)-quinolinone (3d).
ꢀ
1
75%, white solid, mp 97–100 C; H NMR (CDCl3) d
9.13 (br s, 1H), 7.13–7.21 (m, 2H), 6.97 (td, J=7.3,
1.2 Hz, 1H), 6.83 (d, J=8.0Hz, 1H), 3.54–3.60(m,
2H), 3.05 (dd, J=15.4, 6.0Hz, 1H), 2.76 (dd,
J=15.3, 9.1 Hz, 1H), 2.53–2.61 (m, 1H), 1.86–2.04
(m, 3H), 1.62–1.71 (m, 1H); 13C NMR (CDCl3) d
172.1, 140.7, 135.2, 126.5, 125.9, 121.4, 113.5, 43.1,
37.8, 29.4, 28.5, 25.5; MS (EI) m/z 225 (M++2), 223
(M+), 188, 160, 146 (100), 132. Anal. calcd for
C12H14ClNO: C, 64.43; H, 6.31; N, 6.26. Found: C,
64.35; H, 6.52; N, 6.17.
3-(3-Chloropropyl)-6-nitro-3,4-dihydro-2(1H)-quinolinone
(4d). 89%, white solid, mp 206–208 ꢀC; 1H NMR
(DMSO-d6) d 10.69 (br s, 1H), 8.11 (s, 1H), 8.05 (d,
J=8.8 Hz, 1H), 6.98 (d, J=8.8 Hz, 1H), 3.64 (t, J=6.1
Hz, 2H), 3.13 (dd, J=15.9, 6.1 Hz, 1H), 2.79 (dd,
J=16.2, 10.2 Hz, 1H), 2.48–2.60 (m, 1H), 1.77–1.91 (m,
3H), 1.37-1.52 (m, 1H); 13C NMR (DMSO-d6) d 176.3,
148.2, 145.6, 128.1, 127.6, 127.6, 118.8, 49.2, 41.9, 33.5,
33.4, 30.6; MS (EI) m/z 270(M ++2), 268 (M+), 233,
205, 191 (100), 177, 145, 130, 117. Anal. calcd for
C12H13ClN2O3: C, 53.64; H, 4.88; N, 10.43. Found: C,
53.28; H, 4.95; N, 10.34.
3-(3-Fluoropropyl)-3,4-dihydro-2(1H)-quinolinone (3e).
ꢀ
1
61%, white solid, mp 92–93 C; H NMR (CDCl3) d
8.44 (br s, 1H), 7.14–7.21 (m, 2H), 6.98 (t, J=7.5 Hz,
1H), 6.78 (d, J=7.6 Hz, 1H), 4.47 (dt, J=47.1, 5.7 Hz,
2H), 3.05 (dd, J=15.6, 5.6 Hz, 1H), 2.77 (dd, J=15.4,
9.4 Hz, 1H), 2.55–2.63 (m, 1H), 1.73–2.00 (m, 3H),
1.58–1.66 (m, 1H); 13C NMR (CDCl3) d 172.1, 135.2,
126.5, 125.9, 121.4, 121.4, 113.5, 82.2 (d, J=164 Hz),
38.0, 29.3, 26.3 (d, J=19 Hz), 24.0(d, J=5 Hz); MS
(EI) m/z 207 (M+), 146 (100), 132, 117, 106. Anal. calcd
for C12H14FNO: C, 69.55; H, 6.81; N, 6.76. Found: C,
69.61; H, 6.97; N, 6.75.
3-(3-Fluoropropyl)-6-nitro-3,4-dihydro-2(1H)-quinolinone
(4e). 77%, white solid, mp 208–209 ꢀC; 1H NMR
(CDCl3) d 8.65 (br s, 1H), 8.10–8.14 (m, 2H), 6.88 (d,
J=9.2 Hz, 1H), 4.40(dt, J=47.1, 5.5 Hz, 2H), 3.71 (dd,
J=15.8, 5.8 Hz, 1H), 2.88 (dd, J=18.5, 9.8 Hz, 1H),
2.05–2.73 (m, 1H), 2.05–1.57 (m, 4H); 13C NMR
(CDCl3) d 171.3, 143.2, 140.6, 123.1, 122.6, 122.5, 113.9,
82.6 (d, J=161 Hz), 37.1, 28.5, 26.2 (d, J=19 Hz),
24.0(d, J=6 Hz); MS (EI) m/z 252 (M+), 232, 205,
191 (100), 177, 145, 130, 117. HRMS (FAB) m/
General procedure for the synthesis of compounds 4a–4e
To a solution of 3a (586 mg, 3.64 mmol) in 10mL of
concd H2SO4 and 2 mL of water at 0 ꢀC was dropwise
added 6l% HNO3 (0.30 mL, 4.00 mmol). After stirred
for 5 min at 0 ꢀC, the reaction mixture was carefully
poured into 400 mL of ice-water. The resulting pre-
cipitate was filtered and washed with 300 mL of water
and dried under suction for 3 h. The solid was dissolved
in 250mL of EtOAc, which was concentrated with 1.0g
of silica in vacuo. The product 4a (582 mg, 78%) was
obtained by flash column chromatography with 20%
EtOAc/hexane as a white solid.
z
253.0988.
C12H14FN2O3 (MH+) calcd: 253.0988; found:
General procedure for the synthesis of compounds 5a–5e
To a solution of 4a (586 mg, 2.84 mmol) and DDQ (724
mg, 3.13 mmol) in 15 mL of DMF was dropwise added