A. H. Abadi et al. / Bioorg. Med. Chem. 13 (2005) 5759–5765
5763
Mass spectra were made on Hewlett Packard GC–MS,
model 5890, series II. Intermediates 3,19 6,20 and 1521
were prepared by reported procedures. All the new com-
pounds were crystallized from ethanol.
(C19H14ClF3N4O2) C, H, N; EI-MS: m/z 422 (M+) and
424 (M++2).
4.3.2.
2-(7-Trifluoromethylquinolin-4-ylamino)benzoic
acid N0-(2-chloropropionyl)hydrazide (9). Yield 36%;
1
4.1.1.
1-[4-(7-Trifluoromethylquinolin-4-ylamino)phen-
mp 205–207 ꢁC; IR (KBr, cmꢀ1): 3500, 1716, 1700; H
yl]ethanone oxime (4). A mixture of an equimolar
amount of 3 (5 mmol) and hydroxylamine hydrochlo-
ride in ethanol (20 ml) was refluxed for 3 h and left to
cool. The separated solid was filtered, washed with di-
lute ammonia solution and water, dried, and
crystallized.
NMR (DMSO-d6): 1.62–1.66 (d, 3H, CH–CH3), 3.45
(br s, 1H, NH, exchangeable), 4.66–4.70 (q, 1H, CH–
CH3), 7.15–8.97 (m, 9H, aromatic), 10.48 (s, 1H, NH,
exchangeable), 10.68 (s, 1H, NH, exchangeable); Anal.
(C20H16ClF3N4O2) C, H, N.
4.3.3.
2-(7-Trifluoromethylquinolin-4-ylamino)benzoic
Yield 90%; mp 328–330 ꢁC; IR (KBr, cmꢀ1): 3300, 3170;
1H NMR (DMSO-d6): 2.15 (s, 3H, CH3), 7.10–8.75 (m,
9H, aromatic), 9.80 (br s, 1H, OH, exchangeable), 11.20
(s, 1H, NH, exchangeable); Anal. (C18H14F3N3O) C, H,
N; EI-MS: m/z 345 (M+).
acid N0-(3-chloropropionyl)hydrazide (10). Yield 33%;
mp 116–118 ꢁC; IR (KBr, cmꢀ1): 3300, 1723, 1700; H
1
NMR (DMSO-d6): 2.70–2.76 (t, 2H, CO–CH2–), 3.50
(br s, 1H, NH, exchangeable), 3.87–3.87 (t, 2H, CH2Cl),
7.10–9.20 (m, 9H, aromatic), 10.15 (s, 1H, NH,
exchangeable), 10.60 (br s, 1H, NH, exchangeable);
Anal. (C20H16ClF3N4O2) C, H, N; EI-MS: m/z 436
(M+) and 438 (M++2).
4.2. General procedure for the preparation of compounds
7 and 16
A mixture of (5 g, 15 mmol) of 6 or 15 and excess of
thionyl chloride was refluxed for 4 h, excess thionyl
chloride was removed under reduced pressure, and the
residue was refluxed with excess hydrazine hydrate in
alcohol (30 ml) for 6 h. The mixture was left to cool
and then evaporated under reduced pressure. The resi-
due obtained was filtered, washed with water, dried,
and crystallized.
4.3.4.
4-(7-Trifluoromethylquinolin-4-ylamino)benzoic
acid N0-(2-chloroacetyl)hydrazide (17). Yield 70%; mp
190–192 ꢁC; IR (KBr, cmꢀ1): 3300, 1730, 1710; 1H
NMR (DMSO-d6): 3.61 (br s, 1H, NH, exchangeable),
4.21 (s, 2H, CH2Cl), 7.11–9.10 (m, 9H, aromatic),
10.45 (s, 1H, NH exchangeable), 10.62 (s, 1H, NH,
exchangeable); Anal. (C19H14ClF3N4O2) C, H, N.
4.3.5.
4-(7-Trifluoromethylquinolin-4-ylamino)benzoic
4.2.1. 2-(7-Trifluoromethylquinolin-4-ylamino) benzoic
acid hydrazide (7). Yield 95%; mp 233–235 ꢁC; IR
acid N0-(2-chloropropionyl)hydrazide (18). Yield 61%;
mp 310–312 ꢁC; IR (KBr, cmꢀ1): 3450, 1732, 1717; H
1
1
(KBr, cmꢀ1): 3200, 1710; H NMR (DMSO-d6): 4.43
NMR (DMSO-d6): 1.61–1.64 (d, 3H, CH–CH3), 3.45
(br s, 1H, NH, exchangeable), 4.60–4.65 (q, 1H, CH–
CH3), 7.19–8.95 (m, 9H, aromatic), 10.50 (s, 1H, NH,
exchangeable), 10.70 (s, 1H, NH, exchangeable); Anal.
(C20H16ClF3N4O2) C, H, N.
(br s, 2H, NH2, exchangeable), 7.18–8.70 (m, 9H, aro-
matic), 8.94 (br s, 1H, NH exchangeable), 10.8 (br s,
1H, NH exchangeable); Anal. (C17H13F3N4O) C, H, N.
4.2.2. 4-(7-Trifluoromethylquinolin-4-ylamino) benzoic
acid hydrazide (16). Yield 90%; mp 210–212 ꢁC; IR
4.3.6.
4-(7-Trifluoromethylquinolin-4-ylamino)benzoic
1
(KBr, cmꢀ1): 3250, 1720; H NMR (DMSO-d6): 4.10
acid N0-(3-chloropropionyl) hydrazide (19). Yield 80%;
1
(br s, 2H, NH2, exchangeable), 7.10–8.77 (m, 9H, aro-
matic), 9.02 (br s, 1H, NH exchangeable), 10.60 (br s,
1H, NH exchangeable); Anal. (C17H13F3N4O) C, H, N.
mp 217–218 ꢁC; IR (KBr, cmꢀ1): 3320, 1730, 1710; H
NMR (DMSO-d6): 2.70–2.76 (t, 2H, CO–CH2–), 3.50
(br s, 1H, NH, exchangeable), 3.92–3.95 (t, 2H, CH2Cl),
7.15–8.83 (m, 9H, aromatic), 10.22 (s, 1H, NH,
exchangeable), 10.57 (br s, 1H, NH, exchangeable);
Anal. (C20H16ClF3N4O2) C, H, N.
4.3. General procedure for the preparation of compounds
8–10 and 17–19
A mixture of (0.35 g, 1 mmol) of 7 or 16 was refluxed
with (1.2 mmol) of the appropriate acid chloride, viz.,
acetyl chloride, 2-chloropropionyl chloride, and 3-
chloropropionyl chloride in dry benzene (15 ml) and
in the presence of triethylamine (0.1 ml) for 10 h.
The solution was evaporated to dryness; the residue
obtained was filtered, washed with water, and
crystallized.
4.4. General procedure for the preparation of compounds
11–13 and 20–22
A solution of the appropriate chloroalkyl derivative 8–
10 and 17–19 (1.8 mmol) in dry acetonitrile (2 ml) was
treated portionwise with a solution of AgNO3 (0.34 g,
2 mmol) in dry acetonitrile (5 ml) and the whole mixture
was stirred at room temperature for 3 h. The mixture
was then filtered, evaporated to dryness, and the residue
was crystallized from absolute ethanol.
4.3.1. 2-(7-Trifluoromethylquinolin-4-ylamino) benzoic
acid N0-(2-chloroacetyl)hydrazide (8). Yield 43%; mp
235–237 ꢁC; IR (KBr, cmꢀ1): 3500, 1720, 1690; 1H
NMR (DMSO-d6): 3.80 (br s, 1H, NH, exchangeable),
4.21 (s, 2H, CH2Cl), 7.16–8.65 (m, 9H, aromatic),
10.38–10.82 (br m, 2H, NHs, exchangeable); Anal.
4.4.1.
2-(7-Trifluoromethylquinolin-4-ylamino)benzoic
acid N0-(2-nitrooxyacetyl)hydrazide (11). Yield 33%;
mp 200–202 ꢁC; IR (KBr, cmꢀ1): 3124, 1733, 1710; H
NMR (DMSO-d6): 4.20 (s, 2H, CH2), 7.70–8.69 (m,
1