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J. Dietrich et al. / Bioorg. Med. Chem. 18 (2010) 292–304
116.19, 114.05, 109.10, 34.28, 21.38, 17.57 d LC/MS 100.0%, [M]ꢁ
531.2 tR = 7.62 min. HRMS (ESI) (M+1): 533.1907 calcd for
C28H23F3N6O2 (M+1): 533.1835.
=
10.1.7. N-(4-Methyl-3-(3-methyl-4-oxo-3,4-dihydroquinazolin-
6-ylamino)phenyl)-2-(trifluoromethyl)-5-(3-(trifluoromethyl)-
phenyl)-1H-imidazole-4-carboxamide (KIN040)
1H NMR (300 MHz, acetone-d6): d 13.21 (br s, 1H, imid NH), 9.62
(br s, 1H, NH), 8.21–8.25 (m, 2H), 8.06 (s, 1H), 7.90 (s, 1H), 7.59 (d,
1H, J = 2.5 Hz), 7.44–7.54 (m, 3H), 7.32 (s, 1 h), 7.23 (d, 1H,
J = 7.7 Hz), 3.514 (s, 3H), 2.185 (s, 3H). 13C NMR (75 MHz, ace-
10.1.3. 5-(4-Fluorophenyl)-N-(4-methyl-3-(3-methyl-4-oxo-3,4-
dihydroquinazolin-6-ylamino)phenyl)-2-(trifluoromethyl)-1H-
imidazole-4-carboxamide (KIN035)
1H NMR (300 MHz, acetone-d6): d 13.0 (br s, 1H, imid NH), 9.58
(br s, 1H, NH), 8.06 (s, 1H, Ar), 7.93–7.98 (m, 3H), 7.60 (d, 1H,
J = 2.5 Hz), 7.45–7.56 (m, 3H), 7.33 (s, 1H), 7.19–7.26 (m, 3H). 13C
tone-d6): d 161.12, 160.02, 148.88, 145.05, 144.86, 142.24,
141.16, 137.98, 135.92, 134.44 (q, J = 40.5 Hz), 134.40, 134.02,
132.51, 131.50, 130.10 (q, J = 31.9 Hz), 129.70, 128.79, 126.62 (q,
J = 3.9 Hz), 126.08 (q, J = 3.75 Hz), 125.50, 124.91 (q, J = 228.5 Hz)
123.90, 118.95 (q, J = 261.8 Hz), 115.47, 113.14, 109.48, 33.35,
17.25. LC/MS 95.54%, [M]ꢁ = 585.3 tR = 6.87 min. HRMS (ESI)
(M+1): 587.1625 calcd for C28H20F6N6O2 (M+1) = 587.1552. 46.4%
yield.
NMR (75 MHz, acetone-d6):
d 162.62 (d, J = 379 Hz), 161.86,
161.09, 145.06, 144.92, 142.25, 141.14, 138.11, 136.40, 134.33 (q,
J = 41.1 Hz), 132.35 (d, 2C, J = 12.5 Hz), 131.90 (br), 131.48,
128.84, 126.37, 125.25 (br), 123.86, 123.43, 119.02, 115.39 (d, 2C,
J = 2.1 Hz), 115.08, 113.15, 109.39, 30.34, 17.25. LC/MS 96.44% tR =
8.36 min [M]ꢁ = 535.2. HRMS = 536.1657 calcd HRMS = 536.1584.
51.2% yield.
10.1.8. N-(4-Methyl-3-(3-methyl-4-oxo-3,4-dihydroquinazolin-
6-ylamino)phenyl)-2-(trifluoromethyl)-5-(2-(trifluoromethyl)-
phenyl)-1H-imidazole-4-carboxamide (KIN041)
10.1.4. 5-(4-Fluoro-3-methylphenyl)-N-(4-methyl-3-(3-methyl-
4-oxo-3,4-dihydroquinazolin-6-ylamino)phenyl)-2-
1H NMR (300 MHz, acetone-d6): d 13.0 (br s, 1H, imid NH), 9.49
(br s, 1H, NH), 8.10 (dd, 1H, J = 2.2 Hz, J = 5.2 Hz), 7.82–7.86 (m,
2H), 7.65–7.75 (m, 3H), 7.49–7.54 (m, 3H), 7.42 (dd, 1H,
J = 2.7 Hz, J = 8.8 Hz), 7.40 (s, 1H), 7.20 (d, 1H, J = 8.8 Hz), 3.52 (s,
3H), 2.29 (s, 3H). 13C NMR (75 MHz, acetone-d6): d 161.08,
159.36, 148.89, 145.01, 142.15, 141.10, 138.05, 134.44(q,
J = 40.5 Hz), 134.41, 133.45, 132.23, 131.45, 130.26, 129.94,
129.55 (q, J = 30.0 Hz), 128.76, 126.50, 126.29 (q, 5.18 Hz),
125.50, 124.02 (q, J = 271.3 Hz), 123.76, 122.55, 119.04 (q,
J = 267.2 Hz), 115.40, 113.28, 109.39 LC/MS 98.10%, [M]ꢁ = 585.3
tR = 6.56 min. HRMS (ESI) (M+1): 587.1625 calcd for C28H20F6N6O2
(M+1) = 587.1552. 56.7% yield.
(trifluoromethyl)-1H-imidazole-4-carboxamide (KIN037)
1H NMR (300 MHz, acetone-d6): d 13.0 (br s, 1H, imid NH), 9.58
(br s, 1H, NH), 8.11 (s, 1H, Ar), 7.95 (s, 1H), 7.77 (s, 1H), 7.51 (m,
1H), 7.60 (d, 1H, J = 2.5 Hz), 7.56 (d, 1H, J = 8.8 Hz), 7.52 (m, 1H),
7.49 (dd, 1H, J = 8.8 Hz, J = 2.5 Hz), 7.35 (s, 1H), 7.24 (d,
J = 8.2 Hz), 7.118 (t, 1H, J = 9.3 Hz), 3.53 (s, 3H), 2.59 (d, 3H,
J = 3.6 Hz), 2.59 (s, 3H). 13C NMR (75 MHz, acetone-d6):
d
161.121, 160.195 (d, J = 242.2 Hz), 145.04, 144.90, 142.22, 141.16,
138.08, 136.26, 134.43 (q, J = 41.6 Hz), 131.98, 131.49 (d,
J = 5.3 Hz), 149.485, 128.79, 128.37(d, J = 9.7 Hz), 126.35, 126.20
(d, J = 17.2), 125.42 (d, J = 3.3 Hz), 123.91, 123.40, 119.00 (q,
J = 268.8 Hz), 116.60 (d, J = 25.0 Hz), 115.40, 113.01, 109.463,
33.35, 17.25, 13.92 (d, J = 3.45 Hz) LC/MS 96.3%, [M]ꢁ = 549.3
tR = 8.28 min. HRMS (ESI) (M+1): 551.1813 calcd for C28H22F4N6O2
(M+1): 551.1740. 54.3% yield.
10.1.9. 5-(3-Chloro-4-fluorophenyl)-N-(4-methyl-3-(3-methyl-
4-oxo-3,4-dihydroquinazolin-6-ylamino)phenyl)-2-(trifluoro-
methyl)-1H-imidazole-4-carboxamide (KIN036)
1H NMR (300 MHz, acetone-d6): d 13.0 (br s, 1H, imid NH), 9.59
(br s, 1H, NH), 8.10 (dd, 1H, J = 2.2 Hz, J = 5.2 Hz), 7.95 (s, 1H), 7.8–
7.9 (m, 2H), 7.61 (d, 1H, J = 2.4 Hz), 7.4–7.58 (m, 3H) 7.37 (t, 1H,
J = 8.9 Hz), 7.30 (s, 1H), 7.24 (d, 1H, J = 8.3 Hz), 3.51 (s, 3H), 2.26
(s, 3H). 13C NMR (75 MHz, acetone-d6): d 161.17, 160.02, 158.47
(d, J = 248.32), 145.03, 144.85, 142.27, 141.14, 137.98, 135.23,
134,76 (q, J = 41.3 Hz), 132.32, 132.17, 131.48, 130.79 (d,
J = 7.65 Hz), 128.84, 126.71, 126.32, 124.02, 123.35, 120.13 (d,
J = 17.65 Hz), 118.99 (q, J = 267.3 Hz), 116.62 (d, J = 21.3 Hz),
115.37, 112.99 (d, 3.3 Hz), 109.37, 33.35, 17.25. LC/MS 96.86%,
[M]ꢁ = 569.3 tR = 8.012 min. HRMS (ESI) (M+1): 571.1267 calcd
for C27H19ClF4N6O2 (M+1) = 571.1194.
10.1.5. 5-(3-Fluoro-4-methylphenyl)-N-(4-methyl-3-(3-methyl-
4-oxo-3,4-dihydroquinazolin-6-ylamino)phenyl)-2-
(trifluoromethyl)-1H-imidazole-4-carboxamide (KIN038)
1H NMR (300 MHz, acetone-d6): d 13.1 (br s, 1H, imid NH), 9.61
(br s, 1H, NH), 8.06 (s, 1H, Ar), 7.93 (d, 1H, J = 2.0 Hz), 7.75 (dd, 1H,
J = 1.6 Hz, J = 11.3 Hz), 7.59 (m, 2H), 7.42–7.56 (m, 2H), 7.22–7.35
(m, 3H), 3.52 (s, 3H), 2.24 (d, 3H, J = 10.4 Hz), 2.10 (s, 3H). 13C
NMR (75 MHz, acetone-d6): d 161.87 (d, J = 246.4 Hz), 160.11,
160.19, 145.06, 144.93, 142.15, 141.13, 138.11, 136.50, 134.32 (q,
J = 41.6 Hz), 133.39 (d, J = 5.2 Hz), 131.95, 131.48, 129.79 (d,
J = 8.5 Hz), 128.77, 126.30, 124.74, 124.504 (d, J = 17.8 Hz),
123.95, 123.38, 119.24 (q, J = 269.0), 115.39, 114.86 (d, J = 22.9),
113.10, 109.40, 33.36, 17.243, 14.04 (d, J = 3.7 Hz). LC/MS 96.3%,
[M]ꢁ = 549.3 tR = 8.36 min. HRMS (ESI) (M+1): 550.1816 calcd for
C28H22F4N6O2 (M+1): 550.1740. 53.6% yield.
10.1.10. N-(4-Methyl-3-(3-methyl-4-oxo-3,4-dihydroquin-
azolin-6-ylamino)phenyl)-2,5-diphenyl-1H-imidazole-4-
carboxamide (KIN043)
1H NMR (300 MHz, acetone-d6): d 13.0 (br s, 1H, imid NH), 9.89
(br s, 1H, NH), 8.19 (d, 2H, J = 7.2 Hz), 8.13 (s, 1H), 8.02 (s, 1H), 7.8–
7.9 (m, 3H), 7.32–7.54 (m, 10H), 7.21 (d, 1H, J = 8.4 Hz), 3.45 (s,
3H), 2.16 (s, 3H). 13C NMR (75 MHz, acetone-d6): d 161.87,
161.34, 149.81, 147.72, 145.67, 145.55, 141.59, 140.00, 138.58,
136.12, 135.14, 132.05, 131.81, 130.33, 130.23, 129.83, 129.54,
129.07, 128.69, 126.75, 125.67, 123.83, 123.28, 116.09, 114.255,
108.32, 34.26, 18.30. HRMS (ESI) (M+1): 527.2190 calcd for
C32H26N6O2 (M+1) = 527.2117. 73.6% yield.
10.1.6. N-(4-Methyl-3-(3-methyl-4-oxo-3,4-dihydroquinazolin-
6-ylamino)phenyl)-2-(trifluoromethyl)-5-(3,4,5-
trimethoxyphenyl)-1H-imidazole-4-carboxamide (KIN039)
1H NMR (300 MHz, acetone-d6): d 13.0 (br s, 1H, imid NH), 9.58
(br s, 1H, NH), 8.07 (s, 1H, Ar), 8.02 (d, J = 1.6 Hz), 7.66 (d,
J = 2.1 Hz), 7.5–7.6 (m, 2H), 7.44 (dd, 1H, J = 1.9 Hz, J = 6.1 Hz),
7.34 (s, 2H), 7.31 (s, 1H), 7.23 (d, 1H, J = 6.3 Hz), 3.78 (s, 6H), 3.51
(s, 3H), 2.26 (s, 3H). 13C NMR (75 MHz, acetone-d6): d 161.14,
160.26, 153.36, 145.12, 144.71, 142.32, 141.25, 139.50, 138.106,
137.50, 133.91 (q, J = 38.9 Hz), 131.46, 128.77, 125.78, 124.21,
123.76, 123.37, 119.05 (q, J = 268.8 Hz), 115.07, 112.49, 109.81,
107.66, 107.44, 60.09, 55.99 (2C), 33.34, 17.22. LC/MS 98.23%,
[M]ꢁ = 607.4 tR = 7.816 min. HRMS (ESI) (M+1): 609.2068 calcd
for C30H27F3N6O5 (M+1): 609.1995. 40.8% yield.
10.1.11. 2-tert-Butyl-N-(4-methyl-3-(3-methyl-4-oxo-3,4-
dihydroquinazolin-6-ylamino)phenyl)-5-p-tolyl-1H-imidazole-
4-carboxamide (KIN042)
1H NMR (300 MHz, acetone-d6): d 11.30 (br s, 1H, imid NH), 9.62
(s, 1H, NH), 8.04 (s, 1H), 7.90 (d, 1H, J = 1.9 Hz), 7.75 (d, 2H,