G.-Z. Liu et al. / Bioorg. Med. Chem. 18 (2010) 1626–1632
1631
112.40, 54.76, 54.69, 53.87, 40.65, 31.66, 31.22, 30.70, 29.62; HR-
MS (ESI), calcd C31H27ClN2O3: [M+H]+ m/z: 511.1788; found:
511.1745.
171.64, 163.71, 157.23, 146.58, 146.53, 139.66, 139.60, 137.66,
137.48, 133.71, 133.51, 133.49, 132.85, 132.83, 132.60, 130.56,
129.01, 126.06, 122.24, 119.98, 111.95, 100.09, 60.37, 55.04,
51.64, 45.53, 40.21, 31.72, 31.24, 30.81, 30.57; HR-MS (ESI), calcd
C33H32ClN3O2: [M+H]+ m/z: 538.2621; found: 538.2601.
4.3.5.4. 1-[(5-(Hydroxyl (phenyl) methyl) furan-2(5H)-one)-4-
methyl]-desloratadine (9c). Yield: 30%. Yellow solid, mp = 116–
118 °C. IR (KBr, cmꢁ1): 1757, 1643, 1589, 1478, 1439, 1174, 1025,
4.3.5.9. 1-[((Z)-5-(4-Hydroxy-2-methoxybenzylidene)furan-
2(5H)-one)-4-methyl]-desloratadine (8h). Yield: 80%. Yellow so-
lid, mp = 168–170 °C. IR (KBr, cmꢁ1): 3418, 2925, 1749, 1635, 1516,
1286, 1209, 1167, 1030; 1H NMR (400 MHz, CDCl3, TMS): d 8.40
(dd, 1H, J = 4.7 Hz, J = 1.2 Hz), 7.46 (m, 2H), 7.19–7.09 (m, 5H),
829, 754, 701. 1H NMR (400 MHz, CDCl3, TMS):
d
8.39 (d,
J = 4.6 Hz, 1H), 7.46–7.29 (m, 6H), 7.17–7.09 (m, 4H), 5.83 (s, 1H,
00
00
00
@C(3 )H), 5.35 (d, J = 2.8 Hz, 1H, C5 H–C7 H), 5.19 (d, J = 2.8 Hz,
00
00
1H, C5 H–C7 H), 3.30 (s, 2H, CH2), 3.39–3.32 (m, 2H), 2.84–2.74
(m, 4H), 2.73–2.43 (m, 2H), 2.42–2.35 (m, 4H); 13C NMR
6.90 (d, J = 8.2 Hz, 1H), 6.35 (s, 1H, @C(7 )H), 6.35 (s, 1H, @C(3 )H),
3.90 (s, 3H, OCH3), 3.49 (s, 2H), 3.41–3.38 (m, 2H), 2.87–2.77 (m,
4H), 2.58–2.46 (m, 2H), 2.36–2.24 (m, 4H); 13C NMR (100.6 MHz,
CDCl3, TMS): d 169.49, 157.09, 156.70, 147.49, 147.03, 146.26,
146.06, 139.34, 137.91, 137.51, 137.44, 133.48, 132.73, 132.66,
130.67, 128.88, 125.94, 125.52, 125.16, 122.21, 114.92, 114.74,
112.57, 111.90, 55.85, 54.89, 54.83, 53.78, 31.62, 31.26, 30.71,
30.56; HR-MS (ESI), calcd C32H29ClN2O4: [M+H]+ m/z: 541.1894;
found: 541.1869.
00
00
(100.6 MHz, CDCl3, TMS):
d 171.76, 156.82, 146.57, 139.49,
139.46, 138.69, 137.57, 137.43, 137.41, 136.48, 133.88, 133.39,
132.94, 130.48, 128.99, 128.33, 128.03, 126.91, 125.87, 122.34,
119.76, 85.88, 85.84, 71.80, 71.75, 55.68, 55.24, 55.05, 54.98,
31.61, 31.40, 30.44, 30.19, 29.65; HR-MS (ESI), calcd C31H29ClN2O3:
[M+H]+ m/z: 513.1945; found: 513.1901.
4.3.5.5. 1-[(5-(3,4,5-Trimethoxybenzylidene)furan-2(5H)-one)-
4-methyl]-desloratadine (8d) (Z/E = 1:1). Yield: 50%. Yellow oil.
IR(KBr, cmꢁ1): 2923, 2361, 2342, 1755, 1638, 1589, 1439, 830,
701; 1H NMR (400 MHz, CDCl3, TMS): d 8.39 (dd, 1H, J = 4.8 Hz,
J = 1.2 Hz), 7.44 (d, 1H, J = 7.6 Hz), 7.17–7.04 (m, 4H), 6.68 (s, 2H),
4.3.5.10. 1-[(5-((2-Chlorophenyl) (hydroxy) methyl) furan-
2(5H)-one)-4-methyl]-desloratadine (9i). Yield: 35%. Pink oil.
IR(KBr, cmꢁ1
) m: 2922, 2361, 2343, 1758, 1646, 1589, 1476, 1439,
6.10 (d, J = 2.7 Hz, 1H, @C(7 )H), 5.78 (s, 1H, @C(3 )H), 3.93 (s, 6H,
OCH3), 3.91 (s, 3H, OCH3), 3.41–3.30 (m, 6H), 2.84–2.07 (m, 8H);
13C NMR (100.6 MHz, CDCl3, TMS): d 169.10, 157.13, 153.29,
153.20, 147.35, 146.42, 139.49, 139.43, 137.79, 137.64, 133.53,
133.13, 132.87, 130.66, 128.99, 128.67, 128.38, 126.10, 122.31,
115.84, 111.45, 108.21, 61.01, 60.96, 56.35, 56.10, 54.98, 53.84,
31.72, 31.43, 30.81, 30.65; HR-MS (ESI), calcd C34H33ClN2O5:
[M+H]+ m/z: 585.2156; found: 585.2151.
1054, 1030, 830, 754; 1H NMR (400 MHz, CDCl3, TMS): d 8.34
(dd, 1H, J = 4.8 Hz, J = 1.2 Hz), 7.68 (m, 1H), 7.45 (d, J = 3.8 Hz,
00
00
00
1H), 7.36 (d, J = 8.0 Hz, 1H), 7.30–7.01 (m, 6H), 6.01 (s, 1H, @C(3 )H),
00
00
5.55 (dd, J = 6.4 Hz, J = 2.0 Hz, 1H, C5 H–C7 H), 5.30 (d, J = 2.0 Hz,
00
00
1H, C5 H–C7 H), 3.35 (s, 2H, CH2), 3.34–3.32 (m, 2H), 2.81–2.52
(m, 4H), 2.51–2.32 (m, 2H), 2.06–2.31 (m, 4H); 13C NMR
(100.6 MHz, CDCl3, TMS):
d 172.71, 166.20, 157.19, 146.44,
139.45, 137.59, 137.49, 137.47, 137.42, 137.17, 137.08, 133.58,
133.55, 133.19, 132.87, 131.33, 131.31, 130.70, 129.14, 129.09,
129.05, 127.19, 126.09, 122.36, 119.93, 119.90, 85.01, 85.00,
68.06, 68.04, 60.41, 55.33, 55.30, 55.09, 55.04, 55.00, 31.73,
31.33, 30.83, 30.77, 30.62, 30.57; HR-MS (ESI), calcd
C31H28Cl2N2O3: [M+H]+ m/z: 547.1555; found: 547.1568.
4.3.5.6. 1-[(5-(4-Chlorobenzylidene)furan-2(5H)-one)-4-methyl]-
desloratadine (8e) (Z/E = 1:1). Yield: 60%. Yellow solid,
mp = 129.3–131.2 °C. IR (KBr, cmꢁ1): 1760, 1588, 1490, 1438, 1409,
1091, 1014, 830. 1H NMR (400 MHz, CDCl3, TMS): d 8.39 (m, 1H),
7.66 (d, J = 8.6 Hz, 1H), 7.43–7.29 (m, 4H), 7.17–7.08 (m, 4H), 6.11
00
00
(d, J = 2.5 Hz, 1H, @C(7 )H), 5.79 (s, 1H, @C(3 )H), 3.38–3.29 (m, 4H),
2.85–2.77 (m, 5H), 2.48–2.34 (m, 5H); 13C NMR (100.6 MHz, CDCl3,
TMS): d 168.27, 156.80, 148.53, 147.78, 146.69, 140.85, 139.53,
137.65, 137.49, 136.08, 135.46, 134.30, 133.37, 133.09, 132.55,
132.28, 131.89, 131.07, 130.42, 129.19, 129.02, 128.65, 127.01,
126.22, 122.39, 109.51, 67.31, 54.96, 51.39, 31.64, 31.49, 30.32,
30.04; HR-MS (ESI), calcd C31H26Cl2N2O2: [M+H]+ m/z: 529.1450;
found: 529.1436.
4.3.5.11. 1-[((Z)-5-(Furan-2-ylmethylene)furan-2(5H)-one)-4-
methyl]-desloratadine (8j). Yield: 75%. Brown oil. IR(KBr, cmꢁ1
)
m
: 1755, 1645, 1474, 1438, 1244, 1085, 1017, 984, 829, 742; 1H
NMR (400 MHz, CDCl3, TMS):
d 8.41 (dd, 1H, J = 4.7 Hz,
J = 1.3 Hz), 7.51 (d, J = 1.5 Hz, 1H), 7.45 (dd, 1H, J = 7.6 Hz,
J = 1.1 Hz), 7.16–7.04 (m, overlap, 5H), 6.54 (d, J = 2.0 Hz, 1H),
00
00
6.53 (s, 1H, @C(7 )H), 6.09 (s, 1H, @C(3 )H), 3.64 (s, 2H, CH2),
3.47–3.38 (m, 2H), 2.83–2.75 (m, 4H), 2.56–2.46 (m, 2H), 2.40–
2.13 (m, 4H); 13C NMR (100.6 MHz, CDCl3, TMS): d 168.81,
157.26, 155.91, 148.95, 146.60, 145.95, 144.04, 139.49, 137.77,
137.69, 137.40, 133.37, 133.22, 132.78, 130.68, 128.93, 126.05,
122.17, 116.04, 115.38, 113.05, 100.30, 55.02, 54.98, 53.89, 31.73,
31.44, 30.84, 30.64; HR-MS (ESI), calcd C29H25ClN2O3: [M+H]+
m/z: 485.1632; found: 485.1623.
4.3.5.7. 1-[((Z)-5-(4-(Methylsulfonyl)benzylidene)furan-2(5H)-
one)-4-methyl]-desloratadine (8f) (Z/E = 1:1). Yield: 65%. Yellow
oil. IR (KBr, cmꢁ1): 1759, 1646, 1590, 1505, 1460, 1422, 1329, 1239,
1127 and 1004. 1H NMR (400 MHz, CDCl3, TMS): d 8.39 (m, 1H),
7.69 (d, J = 8.0 Hz, 2H), 7.69 (m, 1H), 7.48 (d, J = 8.0 Hz, 2H),
00
7.19–7.08 (m, 4H), 6.26 (d, J = 1.60 Hz, 1H, @C(7 )H), 5.91 (s, 1H,
00
@C(3 )H), 3.08 (s, 3H, CH3), 3.41–3.38 (m, 4H), 2.84–2.76 (m, 4H),
4.3.5.12. 1-[((Z)-5-(4-Bromobenzylidene)furan-2(5H)-one)-4-
methyl]-desloratadine (8k). Yield: 80%. Yellow solid, mp = 129.2–
2.41–2.38 (m, 2H), 2.32–2.23 (m, 4H); HR-MS (ESI), calcd
C32H29ClN2O4S: [M+H]+ m/z: 573.1615; found: 573.1611.
130 °C. IR (KBr, cmꢁ1
) m: 1764, 1681, 1586, 1486, 1398, 1224, 1173,
1070, 1010, 829, 759; 1H NMR (400 MHz, CDCl3, TMS): d 8.36 (m,
1H), 7.63 (d, 2H, J = 8.4 Hz), 7.49 (d, 1H, J = 8.3 Hz), 7.32 (d, 2H,
4.3.5.8. 1-[((Z)-5-(4-(Dimethylamino)benzylidene)furan-2(5H)-
one)-4-methyl]-desloratadine (8g). Yield: 40%. Brown solid,
mp = 124.3–126 °C. IR (KBr, cmꢁ1): 2921, 2360, 2341, 1747, 1651,
1603, 1525, 1478, 1438, 1374, 1294, 1154, 919, 906, 874, 830,
750. 1H NMR (400 MHz, CDCl3, TMS): d 8.40 (dd, 1H, J = 4.8 Hz,
J = 1.2 Hz), 7.71 (d, J = 8.8 Hz, 2H, Ph), 7.15–7.07 (m, 5H, Ar), 6.68
(d, J = 8.8 Hz, 2H, Ph), 6.35 (s, 1H, @C(7 )H), 6.00 (s, 1H, @C(3 )H),
3.49 (s, 2H), 3.02 (s, 6H, N(CH3)2), 3.41–3.38 (m, 4H), 2.80–2.74
(m, 4H), 2.32–2.06 (m, 4H); 13C NMR (100.6 MHz, CDCl3, TMS): d
00
J = 8.3 Hz), 7.15–7.06 (m, 4H), 6.13 (s, 1H, @C(7 )H), 5.76 (s, 1H,
00
@C(3 )H), 3.37–3.30 (m, 4H), 2.93–2.76 (m, 4H), 2.45–2.30 (m, 6H);
13C NMR (100.6 MHz, CDCl3, TMS): d 168.13, 156.61, 147.68,
146.41, 141.23, 139.39, 137.56, 135.97, 133.30, 132.87, 132.27,
131.95, 131.42, 131.40, 130.31, 128.91, 128.88, 127.21, 126.03,
122.29, 121.31, 109.59, 67.09, 54.72, 51.19, 31.50, 31.29, 30.15,
29.86; HR-MS (ESI), calcd C31H26BrClN2O2: [M+H]+ m/z: 573.0944;
found: 573.0916.
00
00