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(DMSO-d6): d 10.89 (s, 1H, NH amide), 8.87 (s, 1H, H-5),
8.13 (d, 1H, H-8, Jortho = 9.0 Hz), 7.97 (d, 1H, H-7, Jortho
= 9.0 Hz), 7.83–7.26 (m, 9H, toluic acid and phenyl ring),
7.06 (d, 2H, H-2 and H-6 phenol, Jortho = 8.4 Hz), 6.85 (d, 2H,
H-3 and H-5 phenol, Jortho = 8.4 Hz), 5.31 (s, 2H, CH2O),
3.37 (s, 2H, NH2 under H2O signal), 2.51 (q, 2H, CH2CH3
under DMSO signal), 2.32 (s, 3H, CH3), 1.10 (t, 3H,
CH2CH3); MS: m/z 487 [M+], 366, 239, 210, 118. Anal.
C32H29N3O2.2/3 H2O (C, H, N).
6.1.5.12. 4-Amino-6-[2-(4-fluorophenoxymethyl)benzamido]-
quinazoline (4s). Compound 4s was obtained in 68% yield,
1
m.p. >300 °C (ethanol); H NMR (DMSO-d6): d 10.90 (s,
1H, NH amide), 8.74 (as, 1H, H-5), 8.05 (s, 1H, H-2), 7.90
(ad, 1H, H-7, Jortho = 8.8 Hz), 7.70–7.40 (m, 5H, H-8 and
toluic acid), 7.12–6.80 (m, 6H, NH2 and phenol), 5.30 (s, 2H,
CH2O); MS: m/z 388 [M+], 292, 239, 210, 118. Anal.
C22H17FN4O2 (C, H, N).
6.1.5.13. 4-Amino-6-[2-(4-ethylphenoxymethyl)benzamido]-
2-methylquinazoline (4t). Compound 4t was obtained in
35% yield, m.p. 249–251 °C (methanol); 1H NMR (DMSO-
d6): d 12.18 (s, 1H, C4=NH tautomeric form of NH2), 10.72
(s, 1H, NH amide), 8.59 (d, 1H, H-5, Jmeta = 2.2 Hz), 7.98
(dd, 1H, H-7, Jortho = 8.8 Hz, Jmeta = 2.2 Hz), 7.70–7.40 (m,
5H, H-8 and toluic acid), 7.05 (d, 2H, H-2 and H-6 phenol,
Jortho = 8.8 Hz), 6.83 (d, 2H, H-3 and H-5 phenol, Jortho
= 8.8 Hz), 5.28 (s, 2H, CH2O), 2.47 (q, 2H, CH2CH3 partially
under DMSO signal), 2.34 (s, 3H, CH3), 1.10 (t, 3H,
CH2CH3); MS: m/z 412 [M+], 291, 239, 210, 118. Anal.
C25H24N4O2.1/3 H2O (C, H, N).
6.1.5.8. 4-Amino-6-[2-(4-fluorophenoxymethyl)benzamido]-
2-methyl-3-phenylquinoline (4o). Compound 4o was ob-
1
tained in 40% yield, m.p. 100 °C (DSC) (methanol); H
NMR (DMSO-d6): d 10.88 (s, 1H, NH amide), 8.85 (s, 1H,
H-5), 8.05 (d, 1H, H-8, Jortho = 9.0 Hz), 7.95 (d, 1H, H-7,
Jortho = 9.0 Hz), 7.88–7.29 (m, 9H, toluic acid and phenyl
ring), 7.22–6.87 (m, 4H, phenol), 5.33 (s, 2H, CH2O), 3.39
(s, 2H, NH2 under H2O signal), 2.31 (s, 3H, CH3); MS: m/z
477 [M+], 366, 229, 118.Anal. C30H24FN3O2.H2O (C, H, N).
6.1.5.9. Ethyl 4-amino-6-[2-(4-ethylphenoxymethyl)benza-
mido]-2-methyl-3-quinolinecarboxylate (4p). Compound 4p
was obtained in 35% yield, m.p. 154–156 °C (ethyl
6.1.5.14. 4-Amino-6-[2-(4-fluorophenoxymethyl)benzamido]-
1
acetate/hexane); H NMR (DMSO-d6): d 10.63 (s, 1H, NH
2-methylquinazoline (4u). Compound 4u was obtained in
1
amide), 8.56 (d, 1H, H-5, Jmeta = 1.8 Hz), 7.75 (dd, 1H, H-7,
Jortho = 9.2 Hz, Jmeta = 1.8 Hz), 7.72–7.43 (m, 7H, H-8, NH2
and toluic acid), 7.06 (d, 2H, H-2 and H-6 phenol, Jortho
= 8.6 Hz), 6.85 (d, 2H, H-3 and H-5 phenol, Jortho = 8.6 Hz),
5.30 (s, 2H, CH2O), 4.35 (q, 2H, OCH2CH3), 2.62 (s, 3H,
CH3), 2.51 (q, 2H, CH2CH3 under DMSO signal), 1.35 (t,
3H, OCH2CH3), 1.10 (t, 3H, CH2CH3); MS: m/z 483 [M+],
438, 362, 316, 288, 239, 210, 118. Anal. C29H29N3O4 (C, H,
N).
44% yield, m.p. 284–288 °C (ethanol); H NMR (DMSO-
d6): d 12.17 (s, 1H, C4=NH tautomeric form of NH2), 10.72
(s, 1H, NH amide), 8.58 (d, 1H, H-5, Jmeta = 2.2 Hz), 7.97
(dd, 1H, H-7, Jortho = 8.8 Hz, Jmeta = 2.2 Hz), 7.70–7.40 (m,
5H, H-8 and toluic acid), 7.15–6.80 (m, 4H, phenol), 5.29 (s,
2H, CH2O), 2.34 (s, 3H, 2-CH3); MS: m/z 402 [M+], 291,
118, 112. Anal. C23H19FN4O2 (C, H, N).
6.2. Calorimetric studies
6.1.5.10. Ethyl 4-amino-6-[2-(4-fluorophenoxymethyl)ben-
zamido]-2-methyl-3-quinolinecarboxylate (4q). Compound
4q was obtained in 61% yield, m.p. 143–145 °C (diethyl
The thermal behaviour of compounds 4h–u is summa-
rized in Table 3. A first group (4j,q,r,u) showed a neat
melting peak followed by decomposition.
A second group (4i,m–o) showed a first melting peak in
the 100–150 °C range and a second one in the 230–290°C
range. Between the two, an exothermal peak due to re-
crystallization always appeared.
TGA and FT-IR demonstrated that these compounds lose
crystallization water and undergo a transition from a hy-
drated to an anhydrous form, during the first melting. The
various hydrates have different amount of water in their
crystalline structure. The number of water molecules was
calculated by TGA weight loss for each different substance
and reported in Table 3.
A third group (4h,k) showed neither a melting peak nor
water loss. These compounds readily undergo decomposition
upon reaching a given temperature in the range from 250 to
300 °C.
1
ether); H NMR (DMSO-d6): d 10.63 (s, 1H, NH amide),
8.55 (d, 1H, H-5, Jmeta = 1.8 Hz), 7.78 (dd, 1H, H-7, Jortho
= 9.2 Hz, Jmeta = 1.4 Hz), 7.73–7.44 (m, 7H, H-8, NH2 and
toluic acid), 7.16–6.89 (m, 4H, phenol), 5.32 (s, 2H, CH2O),
4.37 (q, 2H, OCH2CH3), 2.62 (s, 3H, CH3), 1.35 (t, 3H,
OCH2CH3); MS: m/z 473 [M+], 428, 362, 316, 288, 229, 118,
111. Anal. C27H24FN3O4 (C, H, N).
6.1.5.11. 4-Amino-6-[2-(4-ethylphenoxymethyl)benzamido]-
quinazoline (4r). Compound 4r was obtained in 40% yield,
m.p. 232–234 °C (methanol); 1H NMR (DMSO-d6): d 10.66
(s, 1H, NH amide), 8.51 (d, 1H, H-5, Jmeta = 2.2 Hz), 8.34 (s,
1H, H-2), 7.85 (dd, 1H, H-7, Jortho = 10.0 Hz, Jmeta = 2.2 Hz,),
7.75–7.42 (m, 7H, H-8, NH2 and toluic acid), 7.06 (d, 2H,
H-2 and H-6 phenol, Jortho = 8.8 Hz), 6.85 (d, 2H, H-3 and
H-5 phenol, Jortho = 8.8 Hz), 5.30 (s, 2H, CH2O), 2.51 (q, 2H,
CH2CH3 under DMSO signal), 1.09 (t, 3H, CH2CH3); MS:
m/z 398 [M+], 277, 239, 210, 118. Anal. C24H22N4O2 (C, H,
N).
Compound 4p displayed a first melting followed by re-
crystallization and then a second melting. Compound 4t
loses water at about 70 °C and then shows a unique melting
peak at about 240 °C.