2086 J ournal of Medicinal Chemistry, 2004, Vol. 47, No. 8
J o¨nsson et al.
(C), 142.6 (C), 143.9 (C), 158.0 (C), 166.1 (C), 169.3 (C). MS-
ESI: m/z 343 [MH]+. Anal. (C18H15N2O3Cl‚0.038CH2Cl2) C, H,
N.
5-Ch lor o-N-et h yl-1,2-d ih yd r o-4-h yd r oxy-1-m et h yl-2-
oxo-N-p h en yl-3-qu in olin eca r boxa m id e (8c). See method
F above.
5-Ch lor o-1,2-dih ydr o-4-h ydr oxy-1-m eth yl-2-oxo-N-ph en -
yl-N-pr opyl-3-qu in olin ecar boxam ide (8d). 13C NMR (CDCl3)
δ 11.3 (CH3), 20.9 (CH2), 29.8 (CH3), 52.1 (CH2), 105.5 (C),
112.7 (C), 113.3 (CH), 125.4 (CH), 126.6 (2CH), 126.8 (CH),
128.5 (2CH), 131.6 (CH), 132.7 (C), 142.3 (C), 142.6 (C), 157.9
(C), 165.2 (C), 168.8 (C). MS-ESI: m/z 371 [MH]+. Anal.
(C20H19N2O3Cl) C, H, N.
13C NMR (CDCl3) δ 29.8 (CH3), 35.8 (CH3), 55.7 (CH3), 56.9
(CH3), 103.3 (CH), 104.4 (C), 108.5 (CH), 110.0 (C), 111.6 (CH),
120.0 (CH), 128.5 (CH), 128.6 (CH), 131.3 (CH), 132.1 (C),
141.3 (C), 155.3 (C), 157.1 (C), 158.1 (C), 160.3 (C), 165.7 (C).
MS-ESI: m/z 369 [MH]+. Anal. (C20H20N2O5) C, H, N.
1,2-Dih yd r o-4-h yd r oxy-5-m eth oxy-N,1-d im eth yl-2-oxo-
N -[3-(t r iflu or om e t h yl)p h e n yl]-3-q u in olin e ca r b oxa m -
id e (11l). 13C NMR (CDCl3) δ 29.6 (CH3), 36.5 (CH3), 56.9
(CH3), 103.5 (CH), 104.0 (C), 108.5 (CH), 109.5 (C), 123.6 (CF3,
q, J CF ) 272 Hz), 123.3 (CH), 123.8 (CH), 129.2 (CH), 129.6
(CH), 130.8 (C, q, J CCF ) 33.0 Hz), 131.7 (CH), 141.2 (C), 144.0
(C), 157.1 (C), 157.7 (C), 160.2 (C), 165.1 (C). MS-ESI: m/z
407 [MH]+. Anal. (C20H17N2O4F3) C, H, N.
N-(4-F lu or op h en yl)-1,2-d ih yd r o-4-h yd r oxy-5-m eth oxy-
N,1-d im eth yl-2-oxo-3-qu in olin eca r boxa m id e (11o). 13C
NMR (CDCl3), two rotameric forms in equilibrium, δ 29.8
(CH3), 36.9 (CH3), 56.8 (CH3), 103.3 (CH), 104.2 (C), 108.6 (CH),
110.1 (C), 115.4 (2CH, d, J CCF ) 22.5 Hz), 128.0 (2CH, d, J CCCF
) 8.7 Hz), 131.5 (CH), 139.6 (C), 141.3 (C), 157.0 (C), 157.4
(C), 160.2 (C), 161.5 (CF, d, J CF ) 246 Hz), 165.1 (C). MS-ESI:
m/z 357 [MH]+. Anal. (C19H17N2O4F) C, H, N.
5-E t h oxy-1,2-d ih yd r o-4-h yd r oxy-N,1-d im et h yl-2-oxo-
N-p h en yl-3-qu in olin eca r boxa m id e (12b). 13C NMR (CDCl3)
δ 14.6 (CH3), 29.8 (CH3), 36.9 (CH3), 66.2 (CH2), 104.3 (CH),
104.5 (C), 108.4 (CH), 110.3 (C), 126.3 (2CH), 127.2 (CH),
128.6 (2CH), 131.4 (CH), 141.3 (C), 143.7 (C), 156.5 (C), 157.7
(C), 160.3 (C), 165.2 (C). MS-ESI: m/z 353 [MH]+. Anal.
(C20H20N2O4‚0.1H2O) C, H, N.
N-Eth yl-1,2-dih ydr o-4-h ydr oxy-1-m eth yl-5-(m eth ylth io)-
2-oxo-N-p h en yl-3-qu in olin eca r boxa m id e (14c). 13C NMR
(CDCl3) δ 13.0 (CH3), 18.4 (CH3), 29.7 (CH3), 45.4 (CH2), 105.1
(C), 112.1 (CH), 113.2 (C), 121.7 (CH), 126.7 (2CH), 126.8 (CH),
128.5 (2CH), 131.4 (CH), 138.8 (C), 142.3 (2C), 158.5 (C), 165.6
(C), 168.5 (C). MS-ESI: m/z 369 [MH]+. Anal. (C20H20N2O3S)
C, H, N.
1,2-Dih yd r o-4-h yd r oxy-N,1-d im eth yl-5-n itr o-2-oxo-N-
p h en yl-3-qu in olin eca r boxa m id e (15b). 13C NMR (CDCl3)
δ 29.8 (CH3), 38.8 (CH3), 104.7 (C), 106.8 (C), 116.1 (CH), 116.3
(CH), 125.5 (2CH), 127.0 (CH), 128.8 (2CH), 132.2 (CH), 141.3
(C), 143.7 (C), 148.4 (C), 157.8 (C), 163.8 (C), 169.1 (C). MS-
ESI: m/z 354 [MH]+. Anal. (C18H15N3O5‚0.1H2O) C, H, N.
N-Eth yl-N-(2,4-d iflu or op h en yl)-6,7-d ih yd r o-9-h yd r oxy-
6-m et h yl-7-oxo-1,3-d ioxolo[4,5-f]q u in olin e-8-ca r b oxa m -
id e (17b). 13C NMR (CDCl3) δ 29.7 (CH3), 38.5 (CH3), 102.4
(C), 102.8 (CH2), 104.6 (C), 106.1 (CH), 112.5 (CH), 125.7
(2CH), 126.8 (CH), 129.2 (2CH), 135.6 (C), 142.6 (C), 144.1 (C),
144.7 (C), 158.5 (C), 163.7 (C), 169.0 (C). MS-ESI: m/z 367
[MH]+. Anal. (C20H18N2O5‚1H2O) C, H, N.
6-F lu or o-N-(4-flu or op h en yl)-1,2-d ih yd r o-4-h yd r oxy-
N,1-d im eth yl-2-oxo-3-qu in olin eca r boxa m id e (20b). 13C
NMR (CDCl3) δ 29.2 (CH3), 38.8 (CH3), 104.3 (C), 110.2 (CH,
d, J CCF ) 24.0 Hz), 115.6 (CH, d, J CCCF ) 7.7 Hz), 115.6 (2
CH, d, J CCF ) 22.8 Hz), 116.3 (C, d, J CCCF ) 8.3 Hz), 120.6
(CH, d, J CCF ) 24.0 Hz), 127.4 (2CH, d, J CCCF ) 8.4 Hz), 137.0
(C, d, J CCCCF ) 1.6 Hz), 139.8 (C), 157.6 (CF, d, J CF ) 243 Hz),
158.4 (C), 161 2 (CF, d, J CF ) 247 Hz), 164.7 (C), 169.6 (C).
MS-ESI: m/z 345 [MH]+. Anal. (C18H14N2O3F2) C, H, N.
1,2-Dih yd r o-4-h yd r oxy-N,1-d im eth yl-2-oxo-N-p h en yl-
6-(tr iflu or om eth yl)-3-qu in olin eca r boxa m id e (22b). 13C
NMR (CDCl3) δ 29.2 (CH3), 37.7 (CH3), 105.5 (C), 114.3 (CH),
117.1 (C), 122.8 (CH), 123.6 (C, q, J CCF ) 33.2 Hz), 124.0 (CF3,
q, J CF ) 271.6 Hz), 125.6 (2CH), 127.1 (CH), 128.3 (CH), 128.8
(2CH), 141.9 (C), 143.8 (C), 160.5 (C), 164.3 (C), 169.3 (C). MS-
ESI: m/z 377 [MH]+. Anal. (C19H15N2O3F3) H, N. C calcd, C
60.64; found, C 57.3.
5-Ch lor o-1,2-d ih yd r o-4-h yd r oxy-1-m eth yl-N-(1-m eth yl-
eth yl)-2-oxo-N-p h en yl-3-qu in olin eca r boxa m id e (8e). 13
C
NMR (CDCl3) δ 21.0 (CH3), 29.9 (CH3), 48.2 (CH), 109.4 (C),
112.4 (C), 113.5 (CH), 125.1 (CH), 127.9 (2CH), 129.6 (2CH),
131.1 (CH), 131.6 (C), 137.9 (C), 142.1 (C), 158.6 (C), 160.6
(C), 167.5 (C). MS-ESI: m/z 371 [MH]+. Anal. (C20H19N2O3Cl)
C, H, N.
5-Ch lor o-1,2-dih ydr o-4-h ydr oxy-1-m eth yl-2-oxo-N-ph en -
yl-N-(2-p r op en yl)-3-qu in olin eca r boxa m id e (8f). 13C NMR
(CDCl3) δ 29.8 (CH3), 53.3 (CH2), 105.0 (C), 112.7 (C), 113.3
(CH), 117.8 (CH2), 125.5 (CH), 126.0 (2CH), 126.8 (CH), 128.5
(2CH), 131.8 (CH), 132.5 (C), 132.8 (C), 142.7 (C), 142.9 (C),
157.9 (C), 165.7 (C), 168.9 (C). MS-ESI: m/z 369 [MH]+. Anal.
(C20H17N2O3Cl‚0.1H2O) C, H, N.
5-Br om o-N-et h yl-1,2-d ih yd r o-4-h yd r oxy-1-m et h yl-2-
oxo-N-p h en yl-3-q u in olin eca r b oxa m id e (9b ). 13C NMR
(CDCl3 + DMSO-d6) δ 12.9 (CH3), 29.7 (CH3), 45.1 (CH2), 106.4
(C), 113.9 (C), 114.0 (CH), 119.5 (C), 126.8 (2CH), 127.0 (CH),
128.5 (2CH), 129.3 (CH), 131.7 (CH), 141.8 (C), 142.5 (C), 158.3
(C), 163.0 (C), 167.7 (C). MS-ESI: m/z 401 [MH]+. Anal.
(C19H17N2O3Br‚0.3H2O) H, N. C calcd, 56.11; found, 55.0.
N-(2,3-Diflu or op h en yl)-1,2-d ih yd r o-4-h yd r oxy-5-m eth -
oxy-N,1-d im et h yl-2-oxo-3-q u in olin eca r b oxa m id e (11f).
13C NMR (CDCl3) δ 29.8 (CH3), 35.9 (CH3), 57.0 (CH3), 103.5
(CH), 104.2 (C), 108.5 (CH), 109.0 (C), 116.4 (CH, d, J CCF
)
17.0 Hz), 123.1 (CH), 124.1 (CH), 131.9 (CH), 133.0 (C, d, J CCF
) 8.7 Hz), 141.4 (C), 146.8 (CF, dd, J CF ) 253 Hz, J CCF ) 13.2
Hz), 150.8 (CF, dd, J CF ) 249 Hz, J CCF ) 11.6 Hz), 157.3 (C),
158.6 (C), 160.4 (C), 165.3 (C). MS-ESI: m/z 375 [MH]+. Anal.
(C19H16N2O4F2) C, H, N.
N-(2,5-Diflu or op h en yl)-1,2-d ih yd r o-4-h yd r oxy-5-m eth -
oxy-N,1-d im et h yl-2-oxo-3-q u in olin eca r b oxa m id e (11g).
13C NMR (CDCl3 + TFA), two rotameric forms in equilibrium,
δ 31.0 (CH3), 37.2 (CH3), 57.2 (CH3), 104.4 (C), 105.0 (CH),
105.7 (C), 109.5 (CH), 115.4 (CH, d, J CCF ) 25.2 Hz), 116.8
(CH), 117.4 (CH, dd, J CCF ) 23.0 Hz), J CCCCF ) 7.9 Hz), 130.0
(C, dd, J CCF ) 22.9 Hz, J CCCF ) 14.3 Hz), 133.9 (CH), 141.0
(C), 153.9 (CF, d, J CF ) 244 Hz), 157.6 (C), 157.7 (CF, d, J CF
) 240 Hz), 161.4 (C), 161.7 (C), 167,6 (C). MS-ESI: m/z 375
[MH]+. Anal. (C19H16N2O4F2) C, H, N.
N-(2,4-Diflu or op h en yl)-1,2-d ih yd r o-4-h yd r oxy-5-m eth -
oxy-N,1-d im eth yl-2-oxo-3-qu in olin eca r boxa m id e (11h ).
13C NMR (CDCl3), two rotameric forms in equilibrium, δ 29.9
(CH3), 36.0 (CH3, d, J CNCCF ) 2.2 Hz), 56.9 (CH3), 103.5 (CH),
104.2 (C), 104.6 (CH, dd, J CCF ) 23.9 and 26.0 Hz), 108.6 (CH),
109.2 (C), 111.0 (CH, dd, J CCF ) 22.0 Hz, J CCCCF ) 3.6 Hz),
127.4 (C, dd, J CCF ) 12.5 Hz, J CCCCF ) 4.0 Hz), 130.0 (CH, d,
J CCCF ) 9.9 Hz), 131.8 (CH), 141.4 (C), 157.2 (C), 158.4 (CF,
dd, J CF ) 254 Hz, J CCCF ) 12.6 Hz), 158.5 (C), 160.3 (C), 161.7
(CF, dd, J CF ) 249 Hz, J CCCF ) 11.2 Hz), 165.5 (C). MS-ESI:
m/z 375 [MH]+. Anal. (C19H16N2O4F2) C, H, N.
N-(2-Ch lor op h en yl)-1,2-d ih yd r o-4-h yd r oxy-5-m eth oxy-
N,1-d im et h yl-2-oxo-3-q u in olin eca r b oxa m id e (11i). 13C
NMR (CDCl3), two rotameric forms in equilibrium, δ 29.8
(CH3), 35.9 (CH3), 56.9 (CH3), 103.4 (CH), 104.3 (C), 108.4 (CH),
109.4 (C), 127.0 (CH), 128.9 (CH), 129.6 (CH), 130.1 (CH),
131.7 (CH), 132.4 (C), 140.7 (C), 141.3 (C), 157.2 (C), 158.6
(C), 160.5 (C), 165.5 (C). MS-ESI: m/z 373 [MH]+. Anal.
(C19H17N2O4Cl‚0.4H2O) C, H, N.
6-E t h oxy-N-(4-flu or op h en yl)-1,2-d ih yd r o-4-h yd r oxy-
N,1-d im eth yl-2-oxo-3-qu in olin eca r boxa m id e (24b). 13C
NMR (CDCl3) δ 14.7 (CH3), 29.1 (CH3), 38.8 (CH3), 64.0 (CH2),
103.8 (C), 106.4 (CH), 115.4 (CH), 115.5 (2CH, d, J CCF ) 22.8
Hz), 115.8 (C), 122.7 (CH), 127.4 (2CH, d, J CCCF ) 8.6 Hz),
135.1 (C), 140.1 (C), 153.9 (C), 158.3 (C), 161.1 (CF, d, J CF
)
247 Hz), 165.4 (C), 170.1 (C). MS-ESI: m/z 371 [MH]+. Anal.
(C20H19N2O4F) N. C, H calcd, C 64.85, H 5.17; found, C 61.4,
H 4.71. Purity ) 90% (contains 5% of the 6-hydroxy analogue).
1,2-Dih yd r o-4-h yd r oxy-5-m et h oxy-N-(2-m et h oxyp h e-
n yl)-N,1-d im et h yl-2-oxo-3-q u in olin eca r b oxa m id e (11j).