Journal of Medicinal Chemistry
Article
phenyl)-7,7-dimethyl-7,8-dihydroquinoline-2,5(1H,6H)-dione as a
TFA salt. LCMS: m/z (M + H)+ = 491; 1H NMR (400 MHz,
DMSO-d6): δ 9.05 (s, 1H), 8.22 (s, 1H), 8.13−8.04 (m, 2H), 7.61−
7.49 (m, 3H), 7.37 (dd, J = 7.7, 1.6 Hz, 1H), 7.31 (dd, J = 8.5, 1.2 Hz,
1H), 7.17 (td, J = 7.6, 1.2 Hz, 1H), 3.77 (s, 3H), 2.61−2.51 (m, 2H),
2.250−2.20 (m, 2H), 0.98 (s, 3H), 0.94 (s, 3H); HRMS (ESI): m/z
(M + H)+ calcd for C27H24ClN2O3S, 491.1191; found, 491.1203.
Retention time = 3.86 min.
1-([1,1′-Biphenyl]-2-yl)-3-(4-(4-chlorophenyl)thiazol-2-yl)-7,7-di-
methyl-7,8-dihydroquinoline-2,5(1H,6H)-dione (34). This com-
pound was prepared using Method 10 using [1,1′-biphenyl]-2-
amine in step 3 to afford 1-([1,1′-biphenyl]-2-yl)-3-(4-(4-
chlorophenyl)thiazol-2-yl)-7,7-dimethyl-7,8-dihydroquinoline-2,5-
1
(1H,6H)-dione as a TFA salt. LCMS: m/z (M + H)+ = 537.2; H
NMR (400 MHz, DMSO-d6): δ 8.92 (s, 1H), 8.22 (s, 1H), 8.13−7.99
(m, 2H), 7.75−7.58 (m, 2H), 7.58−7.44 (m, 2H), 7.24 (qq, J = 7.1,
3.8, 3.0 Hz, 7H), 2.56 (d, J = 18.0 Hz, 1H), 2.40 (s, 1H), 2.18 (d, J =
16.2 Hz, 1H), 2.00 (d, J = 18.0 Hz, 1H), 0.91 (s, 3H), 0.48 (s, 3H);
HRMS (ESI): m/z (M + H)+ calcd for C32H26ClN2O2S, 537.139;
found, 537.1398. Retention time = 4.037 min.
3-(4-(4-Chlorophenyl)thiazol-2-yl)-1-(2-ethoxyphenyl)-7,7-di-
methyl-7,8-dihydroquinoline-2,5(1H,6H)-dione (29). This com-
pound was prepared using Method 10 using 2-ethoxyaniline in step
3 to afford 3-(4-(4-chlorophenyl)thiazol-2-yl)-1-(2-ethoxyphenyl)-
7,7-dimethyl-7,8-dihydroquinoline-2,5(1H,6H)-dione as a TFA salt.
3-(4-(4-Chlorophenyl)thiazol-2-yl)-1-(2-hydroxyphenyl)-7,7-di-
methyl-7,8-dihydroquinoline-2,5(1H,6H)-dione (35). This com-
pound was prepared using Method 10 using 2-aminophenol in step
3 to afford 3-(4-(4-chlorophenyl)thiazol-2-yl)-1-(2-hydroxyphenyl)-
7,7-dimethyl-7,8-dihydro-quinoline-2,5(1H,6H)-dione as a TFA salt.
1
LCMS: m/z (M + H)+ = 505.1; H NMR (400 MHz, DMSO-d6): δ
9.04 (s, 1H), 8.20 (s, 1H), 8.07 (d, J = 8.7 Hz, 2H), 7.57−7.48 (m,
3H), 7.34 (dd, J = 7.7, 1.7 Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.14 (t, J
= 7.6 Hz, 1H), 4.06 (q, J = 6.9 Hz, 2H), 2.60 (d, J = 17.8 Hz, 1H),
2.50 (d, J = 16.2 Hz, 1H), 2.40 (d, J = 16.3 Hz, 1H), 2.16 (d, J = 17.7
Hz, 1H), 1.11 (t, J = 6.9 Hz, 3H), 0.97 (s, 3H), 0.93 (s, 3H); HRMS
(ESI): m/z (M + H)+ calcd for C28H26ClN2O3S, 505.1347; found,
505.1354. Retention time = 3.927 min.
1
LCMS: m/z (M + H)+ = 477.1; H NMR (400 MHz, DMSO-d6): δ
10.14 (s, 1H), 9.03 (s, 1H), 8.20 (s, 1H), 8.07 (d, J = 8.4 Hz, 2H),
7.52 (d, J = 8.3 Hz, 2H), 7.41−7.33 (m, 1H), 7.24 (dd, J = 7.9, 1.6
Hz, 1H), 7.07 (d, J = 8.2 Hz, 1H), 6.99 (t, J = 7.6 Hz, 1H), 2.57 (d, J
= 17.8 Hz, 1H), 2.45 (s, 2H), 2.29 (d, J = 17.7 Hz, 1H), 0.97 (s, 3H),
0.94 (s, 3H); HRMS (ESI): m/z (M + H)+ calcd for C26H22ClN2O3S,
477.1034; found, 477.1046. Retention time = 3.642 min.
3-(4-(4-Chlorophenyl)thiazol-2-yl)-1-(2-isopropoxyphenyl)-7,7-
dimethyl-7,8-dihydroquinoline-2,5(1H,6H)-dione (30). This com-
pound was prepared using Method 10 using 2-isopropoxyaniline in
step 3 to afford 3-(4-(4-chlorophenyl)thiazol-2-yl)-1-(2-isopropox-
yphenyl)-7,7-dimethyl-7,8-dihydroquinoline-2,5(1H,6H)-dione as a
3-(4-(4-Chlorophenyl)thiazol-2-yl)-7,7-dimethyl-1-(2-phenoxy-
phenyl)-7,8-dihydroquinoline-2,5(1H,6H)-dione (36). This com-
pound was prepared using Method 10 using 2-phenoxyaniline in
step 3 to afford 3-(4-(4-chlorophenyl)thiazol-2-yl)-7,7-dimethyl-1-(2-
phenoxyphenyl)-7,8-dihydroquinoline-2,5(1H,6H)-dione as a TFA
1
TFA salt. LCMS: m/z (M + H)+ = 519.2; H NMR (400 MHz,
DMSO-d6): δ 9.03 (d, J = 1.3 Hz, 1H), 8.19 (d, J = 1.4 Hz, 1H), 8.07
(d, J = 8.6 Hz, 2H), 7.56−7.46 (m, 3H), 7.34 (d, J = 7.7 Hz, 1H),
7.29 (d, J = 8.4 Hz, 1H), 7.12 (t, J = 7.0 Hz, 1H), 4.63 (h, J = 6.0 Hz,
1H), 2.62 (d, J = 17.7 Hz, 1H), 2.50 (d, J = 16.1 Hz, 1H), 2.40 (d, J =
16.3 Hz, 1H), 2.15 (d, J = 17.7 Hz, 1H), 1.13 (d, J = 5.9 Hz, 3H),
1.04 (d, J = 6.0 Hz, 3H), 0.97 (s, 3H), 0.93 (s, 3H); HRMS (ESI): m/
z (M + H)+ calcd for C29H28ClN2O3S, 519.1504; found, 519.1492.
Retention time = 4.026 min.
1
salt. LCMS: m/z (M + H)+ = 553.1; H NMR (400 MHz, DMSO-
d6): δ 8.99 (s, 1H), 8.20 (s, 1H), 8.05 (d, J = 8.3 Hz, 2H), 7.60−7.48
(m, 4H), 7.34 (dt, J = 18.2, 7.6 Hz, 3H), 7.08 (dt, J = 7.6, 3.3 Hz,
2H), 6.98 (d, J = 8.0 Hz, 2H), 2.68 (d, J = 17.8 Hz, 1H), 2.53−2.35
(m, 3H), 1.01 (s, 3H), 0.89 (s, 3H); HRMS (ESI): m/z (M + H)+
calcd for C32H26ClN2O3S, 553.1347; found, 553.1347. Retention time
= 4.048 min.
3-(4-(4-Chlorophenyl)thiazol-2-yl)-7,7-dimethyl-1-(o-tolyl)-7,8-
dihydroquinoline-2,5(1H,6H)-dione (31). This compound was
prepared using Method 10 using o-toluidine in step 3 to afford 3-
(4-(4-chlorophenyl)thiazol-2-yl)-7,7-dimethyl-1-(o-tolyl)-7,8-dihy-
droquinoline-2,5(1H,6H)-dione as a TFA salt. LCMS: m/z (M + H)+
1-(2-(Benzyloxy)phenyl)-3-(4-(4-chlorophenyl)thiazol-2-yl)-7,7-
dimethyl-7,8-dihydroquinoline-2,5(1H,6H)-dione (37). This com-
pound was prepared using Method 10 using 2-(benzyloxy)aniline in
step 3 to afford 1-(2-(benzyloxy)phenyl)-3-(4-(4-chlorophenyl)-
thiazol-2-yl)-7,7-dimethyl-7,8-dihydroquinoline-2,5(1H,6H)-dione as
1
= 475.1; H NMR (400 MHz, DMSO-d6): δ 9.07 (s, 1H), 8.21 (s,
1
a TFA salt. LCMS: m/z (M + H)+ = 567.1; H NMR (400 MHz,
1H), 8.07 (d, J = 8.2 Hz, 2H), 7.60−7.39 (m, 5H), 7.32 (d, J = 7.6
Hz, 1H), 2.56 (d, J = 17.8 Hz, 1H), 2.46 (d, J = 8.1 Hz, 2H), 2.12 (d,
J = 17.9 Hz, 1H), 2.00 (s, 3H), 0.97 (s, 3H), 0.94 (s, 3H); HRMS
(ESI): m/z (M + H)+ calcd for C27H24ClN2O2S, 475.1242; found,
475.1249. Retention time = 3.934 min.
DMSO-d6): δ 9.02 (s, 1H), 8.21 (s, 1H), 8.07 (d, J = 8.5 Hz, 2H),
7.58−7.49 (m, 3H), 7.43−7.34 (m, 2H), 7.19 (dd, J = 7.4, 3.7 Hz,
6H), 5.22−5.09 (m, 2H), 2.58 (d, J = 17.8 Hz, 1H), 2.46 (d, J = 16.1
Hz, 1H), 2.35 (d, J = 16.2 Hz, 1H), 2.17 (d, J = 17.9 Hz, 1H), 0.95 (s,
3H), 0.82 (s, 3H); HRMS (ESI): m/z (M + H)+ calcd for
C33H28ClN2O3S, 567.1504; found, 567.1516. Retention time = 3.99
min.
3-(4-(4-Chlorophenyl)thiazol-2-yl)-1-(2-ethylphenyl)-7,7-dimeth-
yl-7,8-dihydroquinoline-2,5(1H,6H)-dione (32). This compound was
prepared using Method 10 using 2-ethylaniline in step 3 to afford 3-
(4-(4-chlorophenyl)thiazol-2-yl)-1-(2-ethylphenyl)-7,7-dimethyl-7,8-
dihydroquinoline-2,5(1H,6H)-dione as a TFA salt. LCMS: m/z (M +
1-(2-Aminophenyl)-3-(4-(4-chlorophenyl)thiazol-2-yl)-7,7-di-
methyl-7,8-dihydroquinoline-2,5(1H,6H)-dione (38). This com-
pound was prepared using Method 10 using benzene-1,2-diamine in
step 3 to afford 1-(2-aminophenyl)-3-(4-(4-chlorophenyl)thiazol-2-
yl)-7,7-dimethyl-7,8-dihydroquinoline-2,5(1H,6H)-dione as a TFA
1
H)+ = 489.2; H NMR (400 MHz, DMSO-d6): δ 9.08 (s, 1H), 8.22
(s, 1H), 8.13−8.05 (m, 2H), 7.58−7.49 (m, 4H), 7.49−7.41 (m, 1H),
7.32 (d, J = 7.7 Hz, 1H), 2.63−2.50 (m, 1H), 2.49−2.40 (m, 2H),
2.34 (dd, J = 15.1, 7.5 Hz, 1H), 2.32−2.19 (m, 1H), 2.14 (d, J = 17.9
Hz, 1H), 1.08 (t, J = 7.6 Hz, 3H), 0.98 (s, 3H), 0.94 (s, 3H); HRMS
(ESI): m/z (M + H)+ calcd for C28H26ClN2O2S, 489.1398; found,
489.1417. Retention time = 4.023 min.
1
salt. LCMS: m/z (M + H)+ = 476.1; H NMR (400 MHz, DMSO-
d6): δ 9.00 (s, 1H), 8.18 (s, 1H), 8.07 (d, J = 8.2 Hz, 2H), 7.52 (d, J =
8.2 Hz, 2H), 7.18 (t, J = 7.8 Hz, 1H), 6.96 (d, J = 7.1 Hz, 1H), 6.83
(d, J = 8.1 Hz, 1H), 6.66 (t, J = 7.5 Hz, 1H), 5.30 (s, 2H), 2.57 (d, J =
17.7 Hz, 1H), 2.47 (s, 1H), 2.35 (d, J = 16.3 Hz, 1H), 2.25 (d, J =
17.7 Hz, 1H), 0.96 (s, 6H); HRMS (ESI): m/z (M + H)+ calcd for
C26H23ClN3O2S, 476.1194; found, 476.1207. Retention time = 3.721
min.
3-(4-(4-Chlorophenyl)thiazol-2-yl)-1-(2-isopropylphenyl)-7,7-di-
methyl-7,8-dihydroquinoline-2,5(1H,6H)-dione (33). This com-
pound was prepared using Method 10 using 2-isopropylaniline in
step 3 to afford 3-(4-(4-chlorophenyl)thiazol-2-yl)-1-(2-isopropyl-
phenyl)-7,7-dimethyl-7,8-dihydroquinoline-2,5(1H,6H)-dione as a
3-(4-(4-Chlorophenyl)thiazol-2-yl)-7,7-dimethyl-1-(2-
(methylamino)phenyl)-7,8-dihydroquinoline-2,5(1H,6H)-dione
(39). This compound was prepared using Method 10 using N1-
methylbenzene-1,2-diamine in step 3 to afford 3-(4-(4-chlorophenyl)-
thiazol-2-yl)-7,7-dimethyl-1-(2-(methylamino)phenyl)-7,8-dihydro-
quinoline-2,5(1H,6H)-dione as a TFA salt. LCMS: m/z (M + H)+ =
1
TFA salt. LCMS: m/z (M + H)+ = 503.1; H NMR (400 MHz,
DMSO-d6): δ 9.07 (s, 1H), 8.20 (s, 1H), 8.07 (d, J = 8.3 Hz, 2H),
7.64−7.49 (m, 4H), 7.46−7.37 (m, 1H), 7.28 (d, J = 7.4 Hz, 1H),
2.63 (d, J = 17.9 Hz, 1H), 2.55−2.38 (m, 3H), 2.08 (d, J = 17.9 Hz,
1H), 1.14 (d, J = 6.8 Hz, 3H), 1.06 (d, J = 6.8 Hz, 3H), 0.97 (s, 3H),
0.92 (s, 3H); HRMS (ESI): m/z (M + H)+ calcd for C29H28ClN2O2S,
503.1555; found, 503.1558. Retention time = 4.121 min.
1
490.1; H NMR (400 MHz, DMSO-d6): δ 9.01 (d, J = 1.5 Hz, 1H),
8.19 (d, J = 1.4 Hz, 1H), 8.12−8.02 (m, 2H), 7.59−7.47 (m, 2H),
4933
J. Med. Chem. 2021, 64, 4913−4946