Arch. Pharm. Chem. Life Sci. 2009, 342, 265–273
N-(Indazolyl)benzamido Derivatives as CDK1 Inhibitors
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solid, which separated, was filtered off and crystallized to give
pure 9a–o, 11m, 13m, 16, and 17.
N-(1H-Indazol-3-yl)-4-iodobenzamide 9l
Yield: 42%; m.p.: 218–2208C (ethanol); IR (KBr) m [cm– 1]: 3256
1
(NH), 1647 (CO); H-NMR (DMSO-d6) d [ppm]: 7.06–7.95 (a set of
signals, 8H, aromatic protons), 10.83 (s, 1H, NH, exchangeable),
12.79 (s, 1H, NH, exchangeable). Anal. (C14H10IN3O) C, H, N.
N-(1H-Indazol-3-yl)-2-iodobenzamide 9b
Yield: 41%; m.p.: 180–1828C (ethyl acetate / chloroform); IR (KBr)
m [cm– 1]: 3275 (NH), 1658 (CO); 1H-NMR (DMSO-d6) d [ppm]: 7.07–
7.97 (a set of signals, 8H, aromatic protons), 10.82 (s, 1H, NH,
exchangeable), 12.77 (s, 1H, NH, exchangeable). Anal.
(C14H10IN3O) C, H, N.
3,4-Dichloro-N-(1H-indazol-3-yl)benzamide 9m
Yield: 86%; m.p.: 248–2508C (ethyl acetate / chloroform); IR (KBr)
m [cm– 1]: 3402, 3241 (NH), 1673 (CO); 1H-NMR (DMSO-d6) d [ppm]:
7.10–8.36 (a set of signals, 7H, aromatic protons), 11.00 (s, 1H,
NH, exchangeable), 12.86 (s, 1H, NH, exchangeable). Anal.
(C14H9Cl2N3O) C, H, N.
2-Chloro-N-(1H-indazol-3-yl)benzamide 9c
Yield: 98%; m.p.: 139–1408C (ethyl acetate / chloroform); IR (KBr)
m [cm– 1]: 3232 (NH), 1657 (CO); 1H-NMR (DMSO-d6) d [ppm]: 7.08–
7.86 (a set of signals, 8H, aromatic protons), 10.84 (s, 1H, NH,
exchangeable), 12.77 (s, 1H, NH, exchangeable). Anal.
(C14H10ClN3O) C, H, N.
2,6-Difluoro-N-(1H-indazol-3-yl)benzamide 9n
Yield: 56%; m.p.: 190–1938C (ethyl acetate / chloroform); IR (KBr)
m [cm– 1]: 3245 (NH, NH2), 1677 (CO); 1H-NMR (DMSO-d6) d [ppm]:
7.10–7.81 (a set of signals, 7H, aromatic protons), 11.14 (s, 1H,
NH, exchangeable), 12.82 (s, 1H, NH, exchangeable). Anal.
(C14H9F2N3O) C, H, N.
3-Chloro-N-(1H-indazol-3-yl)benzamide 9d
Yield: 32%; m.p.: 165–1688C (ethyl acetate / chloroform); IR (KBr)
m [cm – 1]: 3249 (NH), 1645 (CO); 1H-NMR (DMSO-d6) d [ppm]: 7.06–
8.14 (a set of signals, 8H, aromatic protons), 10.93 (s, 1H, NH,
exchangeable), 12.84 (s, 1H, NH, exchangeable). Anal.
(C14H10ClN3O) C, H, N.
3,4-Dichloro-N-(1H-indazol-5-yl)benzamide 11m
Yield: 65%; m.p.: 270–2728C (ethanol); IR (KBr) m [cm– 1]: 3266,
3153 (NH), 1634 (CO); 1H-NMR (DMSO-d6) d [ppm]: 7.54–8.21 (a set
of signals, 7H, aromatic protons), 10.40 (s, 1H, NH, exchange-
able), 13.04 (s, 1H, NH, exchangeable). Anal. (C14H9Cl2N3O) C, H,
N.
3-Bromo-N-(1H-indazol-3-yl)benzamide 1-carboxamide
9e
Yield: 67%; m.p.: 172–1758C (ethyl acetate / chloroform); IR (KBr)
m [cm– 1]: 3225 (NH), 1644 (CO); 1H-NMR (DMSO-d6) d [ppm]: 7.09–
8.27 (a set of signals, 8H, aromatic protons), 10.93 (s, 1H, NH,
exchangeable), 12.84 (s, 1H, NH, exchangeable). Anal.
(C14H10BrN3O) C, H, N.
3,4-Dichloro-N-(1H-indazol-6-yl)benzamide 13m
Yield: 80%; m.p.: 270–2728C (ethanol); IR (KBr) m [cm– 1]: 3327,
3166 (NH), 1649 (CO); 1H-NMR (DMSO-d6) d [ppm]: 7.38–8.26 (a set
of signals, 7H, aromatic protons), 10.49 (s, 1H, NH, exchange-
able), 12.98 (s, 1H, NH, exchangeable). Anal. (C14H9Cl2N3O) C, H,
N.
3-Fluoro-N-(1H-indazol-3-yl)benzamide 9f
Yield: 67%; m.p.: 150–1528C (petroleum ether / chloroform); IR
(KBr) m [cm– 1]: 3196 (NH), 1637 (CO); 1H-NMR (DMSO-d6) d [ppm]:
7.07–7.96 (a set of signals, 8H, aromatic protons), 10.87 (s, 1H,
NH, exchangeable), 12.82 (s, 1H, NH, exchangeable). Anal.
(C14H10FN3O) C, H, N.
N-(1H-Indazol-3-yl)-2-phenoxyacetamide 16
Yield: 52%; m.p.: 158–1608C (ethyl acetate / chloroform); IR (KBr)
m [cm– 1]: 3358, 3201 (NH), 1678 (CO); 1H-NMR (DMSO-d6) d [ppm]:
4.82 (s, 2H, OCH2), 6.95–7.76 (a set of signals, 9H, aromatic pro-
tons), 10.50 (s, 1H, NH, exchangeable), 12.74 (s, 1H, NH,
exchangeable). Anal. (C15H13N3O2) C, H, N.
N-(1H-Indazol-3-yl)-3-methoxybenzamide 9g
Yield: 98%; m.p.: 205–2078C (ethyl acetate / chloroform); IR (KBr)
m [cm– 1]: 3282 (NH), 1651 (CO); 1H-NMR (DMSO-d6) d [ppm]: 3.85 (s,
3H, OCH3); 7.06–7.74 (a set of signals, 8H, aromatic protons),
10.75 (s, 1H, NH, exchangeable), 12.78 (s, 1H, NH, exchangeable).
Anal. (C15H13N3O2) C, H, N.
N-(1H-indazol-3-yl)-2-phenylacetamide 17
Yield: 98%; m.p.: 229–2308C (chloroform); IR (KBr) m [cm– 1]: 3282
(NH), 1669 (CO); 1H-NMR (DMSO-d6) d [ppm]: 3.40 (s, 2H, CH2),
7.02–7.74 (a set of signals, 9H, aromatic protons), 10.62 (s, 1H,
NH, exchangeable), 12.68 (s, 1H, NH, exchangeable). Anal.
(C15H13N3O) C, H, N.
4-Chloro-N-(1H-indazol-3-yl)benzamide 9h
Yield: 72%; m.p.: 208–2108C (ethyl acetate / chloroform); IR (KBr)
m [cm– 1]: 3264 (NH), 1661, 1646 (CO); 1H-NMR (DMSO-d6) d [ppm]:
7.09–8.14 (a set of signals, 8H, aromatic protons), 10.88 (s, 1H,
NH, exchangeable), 12.82 (s, 1H, NH, exchangeable). Anal.
(C14H10ClN3O) C, H, N.
General procedure for the preparation of N-(3,4-
dichlorophenyl)-1H-indazole-3-carboxamide 23 and N-(5-
chloro-2-iodophenyl)-1H-indazole-3-carboxamide 24
A magnetically stirred solution of diindazolo[2,3-a, 2‘,39-d]pyra-
zine-7,14-dione 21 [13] (2.37 mmol, 0.68 g) and the opportune
aniline 20, 22 (4.74 mmol, 1.2 g) in pyridine (13.5 mL), was left
under magnetic stirring for seven days and then poured into
crushed ice. The solid which separated was filtered off and crys-
tallized to give the compounds 23 and 24.
4-Fluoro-N-(1H-indazol-3-yl)benzamide 9i
Yield: 86%; m.p.: 198–1998C (ethyl acetate); IR (KBr) m [cm– 1]:
3218 (NH), 1646 (CO); 1H-NMR (DMSO-d6) d [ppm]: 7.07–8.22 (a set
of signals, 8H, aromatic protons), 10.83 (s, 1H, NH, exchange-
able), 12.82 (s, 1H, NH, exchangeable). Anal. (C14H10FN3O) C, H, N.
i 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim