Y. Jacquot et al. / Bioorg. Med. Chem. 15 (2007) 2269–2282
2279
5.1.1.3. 4-n-Dodecylaminocoumarin (6c). Prepared by
coupling n-dodecylamine 4c on 4-hydroxycoumarin 1a.
7 on the 4-aminocoumarin 6a. White powder (54%).
ꢀ
1
Mp 174 ꢁC. FTIR (m, cm ): 3348 (S, amine), 3050
ꢀ
1
White powder (30%). Mp 108 ꢁC. FTIR (m, cm ):
321 (VS, amine), 3050 (W, CH aromatic), 2958 (S,
CH n-dodecyl), 2923 (VS, CH n-dodecyl), 2853 (VS,
(W, CH aromatic), 2943 (M, CH cyclopentyl), 2866
(M, CH2 cyclopentyl), 1655 (VS, C@O), 1605 (S,
2
3
C(3)@C(4) coumarin), 1531 (br S, C(3)@C(4) couma-
3
2
1
CH2 n-dodecyl), 1666 (VS, C@O), 1606 (VS,
rin), 1485–1458 (M, C@C aromatic). H NMR (CDCl )
3
C(3)@C(4) coumarin), 1553 (VS, C(3)@C(4) coumarin),
d (ppm): 1.32–1.36 (2H, m, cyclopentyl), 1.51–1.55 (4H,
m, cyclopentyl), 1.84–2.00 (2H, m, cyclopentyl), 2.38
(3H, s, CH ), 3.97 (2H, s, CH ), 4.13 (1H, br s, CH
1
1
(
483–1434 (M, C@C aromatic). H NMR (CDCl ) d
3
3
ppm): 0.89 (3H, t, J = 6.9 Hz, CH n-dodecyl), 1.27–
3
3
2
1
decyl), 3.27 (2H, dd, J = 5.3 Hz, CH –NH n-dodecyl),
.43 (18H, m, CH n-dodecyl), 1.75 (2H, m, CH n-do-
cyclopentyl), 4.36 (1H, br s, NH), 7.01–7.28 (5H, m,
CH aromatic), 7.35–7.38 (1H, d, J = 8.3 Hz, CH aro-
2
2
3
3
2
5
.33 (1H, s, CH@C pyranone), 5.41 (1H, br s, NH),
matic), 7.50 (1H, m, CH aromatic), 7.73 (1H, d,
J = 8.1 Hz, CH aromatic). MS m/z: 334 (M+1)
3
7.24–7.34 (2H, m, CH aromatic), 7.51–7.56 (2H, m,
CH aromatic). MS m/z: 330 (M+1) (C H NO ).
(C H NO ). Anal. Calcd for C H NO : C, 79.25;
2
2
1
31
2
22 23
22 23
2
H, 6.95; N, 4.20. Found: C, 79.01; H, 6.93; N, 4.16.
5
.1.1.4. 4-Phenylethylaminocoumarin (6d). Prepared
by coupling phenylethylamine 4d on 4-hydroxycouma-
rin 1a. White powder (74%). Mp 178 ꢁC. FTIR (m,
cm ): 3265 (S, amine), 3022 (W, CH aromatic), 2940
5.1.2.2. 4-Cyclohexylamino-3-(2-methylbenzyl)couma-
rin (8b). Prepared by coupling methylbenzylbromide 7
on the 4-aminocoumarin 6b. White powder (51%). Mp
ꢀ
1
ꢀ1
(
W, CH ), 2856 (W, CH ), 1659 (VS, C@O), 1609 (VS,
210 ꢁC. FTIR (m, cm ): 3364 (VS, amine), 3067 (W,
2
2
C(3)@C(4) coumarin), 1562 (VS, C(3)@C(4) coumarin),
1
d ) d (ppm): 2.93 (2H, t, J = 5.5 Hz, CH ), 3.49 (2H,
dt, J = 5.5 Hz, CH –NH), 5.20 (1H, s, CH@C pyra-
CH aromatic), 2928 (S, CH cyclohexyl), 2851 (S, CH
cyclohexyl), 1651 (VS, C@O), 1605 (VS, C(3)@C(4) cou-
2
2
1
497–1450 (M, W, C@C aromatic). H NMR (DMSO-
3
marin), 1531 (br VS, C(3)@C(4) coumarin), 1481–1454
6
2
3
1
(M, C@C aromatic). H NMR (CDCl ) d (ppm): 1.00–
2
3
none), 7.16–7.32 (7H, m, CH aromatic), 7.56 (1H, dd,
J = 8.8 Hz, CH aromatic), 7.70 (1H, br s, J = 5.9 Hz,
1.07 (5H, m, cyclohexyl), 1.53–1.69 (3H, br m, cyclohex-
yl), 1.83–1.88 (2H, br m, cyclohexyl), 2.40 (3H, s, CH3),
3.65 (1H, m br, CH cyclohexyl), 3.95 (2H, s, CH ), 4.36
3
3
3
NH), 8.00 (1H, d, J = 8.7 Hz, CH aromatic). MS m/z:
2
2
66 (M+1) (C H NO ).
7
(1H, br s, NH), 6.99–7.29 (5H, m, CH aromatic), 7.40
1
15
2
3
4
1H, dd, J = 8.3 Hz, J = 1.1 Hz, CH aromatic), 7.46–
(
7.55 (1H, m, CH aromatic), 7.60 (1H, dd, J = 8.1 Hz,
3
5.1.1.5. 7-Methoxy-4-n-pentylaminocoumarin (6e).
Prepared by coupling n-pentylamine 4e on 7-methoxy-
4
1
4
J = 1.3 Hz, CH aromatic). MS m/z: 348 (M+1)
(C H NO ). Anal. Calcd for C H NO : C, 79.51;
H, 7.25; N, 4.03. Found: C, 79.48; H, 7.28; N, 4.06.
-hydroxycoumarin 1b. White powder (73%). Mp
2
3
25
2
23 25
2
ꢀ
1
05 ꢁC. FTIR (m, cm ): 3306 (M, amine), 3028 (W,
CH aromatic), 2920 (W, CH n-pentyl), 2851 (W, CH
n-pentyl), 1693 (VS, C@O), 1601 (S, C(3)@C(4) couma-
2
2
5.1.2.3. 4-n-Dodecylamino-3-(2-methylbenzyl)couma-
rin (8c). Prepared by coupling methylbenzylbromide 7
on the 4-aminocoumarin 6c. White powder (42%). Mp
rin), 1543 (S, C(3)@C(4) coumarin), 1497–1431 (M,
1
C@C aromatic). H NMR (CDCl ) d (ppm): 0.90 (3H,
3
3
t, J = 7.1 Hz, CH n-pentyl), 1.38 (4H, m, CH n-pen-
ꢀ1
112 ꢁC. FTIR (m, cm ): 3333 (VS, amine), 3020 (W,
3
2
tyl), 1.74 (2H, m, CH n-pentyl), 3.27 (2H, dd,
2
CH aromatic), 2926 (VS, CH n-dodecyl), 2853 (VS,
CH2 n-dodecyl), 1655 (VS, C@O), 1609 (VS,
2
3
J = 7.1 Hz, CH –NH n-pentyl), 3.85 (3H, s, OCH ),
2
3
5
7
.30 (1H, s, CH@C pyranone), 5.94 (1H, br s, NH),
.23–7.30 (1H, m, CH aromatic), 7.55 (1H, dd,
C(3)@C(4) coumarin), 1541 (br VS, C(3)@C(4) couma-
1
rin), 1487–1452 (M, C@C aromatic). H NMR (CDCl )
3
3
3
3
J = 7.1 Hz, CH aromatic), 7.70 (1H, dd, J = 7.1 Hz,
CH aromatic). MS m/z: 262 (M+1) (C H NO ).
d (ppm): 0.88 (3H, t, J = 6.9 Hz, CH3 n-dodecyl), 1.16–
1.35 (18H, br m, n-dodecyl), 1.41 (2H, br m, n-dodecyl),
1
5
19
3
2.38 (3H, s, CH ), 3.37 (2H, m br, CH –NH n-dodecyl),
3.98 (2H, s, CH ), 4.39 (1H, br s, NH), 7.01–7.26 (5H,
3 2
5
.1.2. Condensation of methylbenzylbromide on the substi-
tuted 4-aminocoumarins (6a–6e). For the preparation of
2
3
m, CH aromatic), 7.35–7.38 (1H, dd, J = 8.3 Hz,
J = 1.0 Hz, CH aromatic), 7.47–7.53 (1H, m, CH aro-
4
4-amino-3-benzylcoumarins, 10 mmol of substituted
4-aminocoumarin and 1.5 equiv of mehylbenzylbromide
7 were stirred at 135–140 ꢁC during 8 h. On cooling at
50 ꢁC, 15 mL of isopropanol was added to the mixture.
3
4
matic), 7.67 (1H, dd, J = 8.1 Hz, J = 1.2 Hz, CH aro-
matic). MS m/z: 434 (M+1) (C H NO ). Anal. Calcd
for C H NO : C, 80.33; H, 9.07; N, 3.23. Found: C,
2
9
39
2
2
9
39
2
The bromhydrate ammonium salt of the awaited product
was precipitated and filtered under vacuum. The precipi-
tate was dissolved in 15 mL of chloroform and washed
three times with 10 mL of an aqueous solution of sodium
hydroxide 0.1 N. After, the organic layer was washed
with twice with 10 mL of water and dried on dry MgSO4.
The mixture was filtered and the solvent evaporated
under vacuum to afford to the awaited 4-amino-3-ben-
zylamincoumarins 8a–8e.
80.58; H, 9.14; N, 3.29.
5.1.2.4. 4-Phenylethylamino-3-(2-methylbenzyl)cou-
marin (8d). Prepared by coupling methylbenzylbromide
7 on the 4-aminocoumarin 6d. White powder (41%).
ꢀ
1
Mp 152 ꢁC. FTIR (m, cm ): 3329 (S, amine), 3032
(M, CH aromatic), 2939 (M, CH ), 1659 (VS, C@O),
2
1605 (VS, C(3)@C(4) coumarin), 1539 (br VS,
C(3)@C(4) coumarin), 1485–1454 (VS, M, C@C aro-
1
matic). H NMR (CDCl ) d (ppm): 2.29 (3H, s, CH ),
3
3
3
2.71 (2H, t, J = 8.22 Hz, CH , 3.65 (2H, m br,
5.1.2.1. 4-Cyclopentylamino-3-(2-methylbenzyl)cou-
marin (8a). Prepared by coupling methylbenzylbromide
2
CH –NH), 3.84 (2H, s, CH ), 4.35 (1H, br s, NH),
2
2