JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
509
on Bruker 400 and 100 MHz instruments, respectively, using tetra- 2-(4-(Cyclopentyloxy)benzylidene)cyclohexanone (5b)
methyl silane (TMS) as an internal standard. Chemical shifts were Crystallisation solvent, water; Yield, 50%; mp: 291–292 C; IR (KBr)
ꢁ
À1
1
reported downfield from TMS in ppm, d units. Mass spectrometry
(
trometer. The purities of the compounds were evaluated by thin
layer chromatography (TLC), which was performed on silica gel G
ꢀ
max/cm 1620 (C ¼ O), 1550, 1642, 1530, 1470 (C ¼ C). H NMR
MS) measurements were performed on a JEOL JMS-600H spec- (DMSO-d
); d: 7.25 (d, 2H, Ar-H, J ¼ 8 Hz), 7.00 (brs, 1H, CH¼), 6.85
d, 2H, Ar-H, J ¼ 8 Hz), 4.90–4.82 (m, 1H, CH), 2.80 (t, 2H, CH
6
(
2
,
J ¼ 4.5 Hz), 2.40 (t, 2H, CH
2
, J ¼ 4.5 Hz), 2.00–1.90 (m, 2H, CH
2
),
1
.85–1.60 (m, 6H, 3CH
2
), 1.50–1.30 (m, 2H, CH
2
), 1.20–1.00 (m, 2H,
(
Merck), and spots were visualised by irradiation with ultraviolet
þ
þ
CH ). MS m/z (%); 272.15 (2.78, M þ2), 271.13 (15.64, M þ1),
light (UV; 254 nm). Compound 3, 4-(cyclopentyloxy)benzaldehyde,
was synthesized in accordance with the method described in the
2
þ
2
70.11 (52.26, M ), 203.08 (26.47), 202.07 (74.25), 201.07 (25.10),
6
1
18 22 2
145.05 (21.80), 107.02 (100.00). Anal. Calcd. for C H O (%): C,
9.96; H, 8.20. Found: C, 80.01; H, 8.50.
literature .
7
General method for the synthesis of a,b-unsaturated ketone
derivatives (4a,b; 5a-c; and 6a,b)
2
-(4-(Cyclopentyloxy)benzylidene)cycloheptanone (5c)
ꢁ
Crystallisation solvent, water; Yield, 60%; mp: 284–285 C; IR (KBr)
À1
1
A solution of 4-(cyclopentyloxy)benzaldehyde 3 (1.9 g, 0.01 mol) in
ethanol (20 ml) was added to a stirred solution of the appropriate (DMSO-d
ꢀ
max/cm 1625 (C ¼ O), 1555, 1540, 1534, 1490 (C ¼ C). H NMR
); d: 7.21 (d, 2H, Ar-H, J ¼ 8.2 Hz), 7.02 (brs, 1H, CH¼),
.80 (d, 2H, Ar-H, J ¼ 8.2 Hz), 4.60–4.50 (m, 1H, CH), 3.20–3.10 (m,
H, CH ), 2.11–1.75 (m, 10H, 5CH ), 1.60–1.47 (m, 6H, 3CH ). MS
6
6
2
ketone (0.03 mol) in ethanol (20 ml) containing NaOH (0.8 g,
.02 mol). The reaction mixture was refluxed for 8 h, cooled and
0
2
2
2
þ
þ
m/z (%); 286.30 (0.2, M þ2), 285.20 (0.8, M þ1), 284.10 (35.00,
the solvent was evaporated under reduced pressure. The resulting
solid was triturated with diethyl ether, filtered, dried, and crystal-
lised from the appropriate solvent.
þ
M ), 216.10 (58.00), 215.10 (100.00), 121.10 (34.00), 120.10 (46.08),
41.10 (37.07). Anal. Calcd. for C19
24 2
H O (%): C, 80.24; H, 8.51.
Found: C, 80.70; H, 8.91.
4
-(4-(Cyclopentyloxy)phenyl)but-3-en-2-one (4a)
3
-(4-(Cyclopentyloxy)benzylidene)-1-methylpiperidin-4-one (6a)
Crystallisation solvent, ethanol; Yield, 40%; melting point (mp):
ꢁ
Crystallisation solvent, water; Yield, 65%; mp: 248–250 C. IR (KBr)
ꢁ
À1
2
1
7
19–220 C; IR (KBr) ꢀmax/cm
1610 (C ¼ O), 1530, 1525, 1510,
À1
1
ꢀ
max/cm 1600 (C ¼ O), 1540, 1525, 1535, 1490 (C ¼ C). H NMR (,
DMSO-d
); d: 7.00 (d, 2H, Ar-H, J ¼ 8 Hz), 6.80–6.71 (m, 3H, Ar-H,
CH¼), 4.60–4.50 (m, 1H, CH), 3.15 (s, 2H, CH ), 2.85 (t, 2H, CH2,
J ¼ 4.5 Hz), 2.60 (t, 2H, CH J ¼ 4.5 Hz), 2.30 (s, 3H, N–CH ),
1
470 (C ¼ C). H NMR (DMSO-d ); d: 7.95 (d, 2H, Ar-H, J ¼ 8 Hz),
6
6
.52 (d, 2H, Ar-H, J ¼ 8 Hz), 7.28 (d, 1H, CH ¼ CH, J ¼ 8.4 Hz), 6.53
2
(d, 1H, CH ¼ CH, J ¼ 8.4 Hz), 4.80–4.70 (m, 1H, CH), 2.26 (s, 3H,
2
,
3
CH ), 1.95–1.85 (m, 2H, CH ), 1.75–1.66 (m, 4H, 2CH ), 1.60–1.52
3
2
2
2 2
2.10–1.90 (m, 2H, CH ), 1.80–1.71 (m, 4H, 2CH ), 1.55–1.45 (m, 2H,
þ
þ
þ
(m, 2H, CH
2
). MS m/z (%); 232.00 (6.39, M þ2), 231.00 (20.31,
CH
2
). MS m/z (%); 287.16 (6.34, M þ2), 286.15 (21.93, M þ1),
þ
þ
þ
M þ1), 230.10 (21.46, M ), 224.00 (52.84), 147.00 (49.56), 142.10 285.15 (8.16, M ), 166.05 (17.92), 161.06 (4.83), 112.08 (34.02),
(
(
100.00), 121.00 (22.93), 100.00 (16.25). Anal. Calcd. for C15
%): C, 78.23; H, 7.88. Found: C, 78.63; H, 8.18.
H
18
O
2
111.09 (42.67), 110.02 (100.00). Anal. Calcd. for C H NO (%): C,
18 23 2
75.76; H, 8.12; N, 4.91. Found: C, 75.86; H, 8.22; N, 5.01.
3
-(4-(Cyclopentyloxy)benzylidene)-1-ethylpiperidin-4-one (6b)
3
-(4-(Cyclopentyloxy)phenyl)-1-(4-methylphenyl)prop-2-en-1-one
4b)
Crystallisation solvent, water; Yield, 85%; mp: 220–222 C; IR (KBr)
ꢁ
Crystallisation solvent, water; Yield, 64%; mp: 240–241 C. IR (KBr)
(
À1
1
ꢁ
ꢀ
max/cm 1635 (C ¼ O), 1560, 1550, 1530, 1485 (C ¼ C). H NMR
(DMSO-d
); d: 7.20 (d, 2H, Ar-H, J ¼ 8 Hz), 6.90–6.80 (m, 3H, Ar-H,
CH¼), 4.90–4.80 (m, 1H, CH), 3.70 (q, 2H, CH CH3, J ¼ 7 Hz), 3.20 (s,
H, CH ), 2.85 (t, 2H, CH ), 2.00–1.90
, J ¼ 4.5 Hz), 2.65 (m, 2H, CH
m, 2H, CH ), 1.75–1.60 (m, 4H, 2CH ), 1.55–1.45 (m, 2H, CH ), 1.02
À1
1
6
ꢀ
max/cm 1615 (C ¼ O), 1540, 1535, 1525, 1480 (C ¼ C). H NMR
2
(CDCl
3
); d: 7.85 (d, 4H, Ar-H, J ¼ 8 Hz), 7.32 (d, 4H, Ar-H, J ¼ 8 Hz),
2
2
2
2
7
4
1
.18 (d, 1H, CH ¼ CH, J ¼ 8.4 Hz), 6.73 (d, 1H, CH ¼ CH, J ¼ 8.4 Hz),
.80–4.72 (m, 1H, CH), 2.36 (s, 3H, CH ), 1.85–1.80 (m, 2H, CH ),
.70–1.62 (m, 4H, 2CH ), 1.60–1.50 (m, 2H, CH ). C NMR (DMSO-
(
(
(
2
2
2
3
2
þ
t, 3H, CH CH , J ¼ 7 Hz). MS m/z (%); 301.30 (18.00, M þ2), 300.20
1
3
2
þ
3
2
2
þ
38.50, M þ1), 299.20 (26.00, M ), 137.90 (36.09), 132.90 (42.35),
d ); d: 198.2, 155.8, 143.3, 135.6, 134.3, 129.1, 128.4, 128.0, 114.8,
6
1
23.90 (100.00), 72.10 (58.50), 58.00 (51.77). Anal. Calcd. for
þ
7
8.3, 32.2, 23.5, 21.0. MS m/z (%); 306.13 (17.66, M ), 238.10
19 2
C H25NO
N, 5.00.
(%): C, 76.22; H, 8.42; N, 4.68. Found: C, 76.62; H, 8.72;
(
(
100.00), 237.08 (87.48), 210.08 (14.15), 209.07 (14.02), 195.06
16.87), 144.03 (42.22). Anal. Calcd. for C21 (%): C, 82.32; H,
22 2
H O
7
.24. Found: C, 82.0 2; H, 7.05.
Synthesis of ethyl 6-amino-5-cyano-4-(4-(cyclopentyloxy)phenyl)-
-methyl-4H-pyran-3-carboxylate (7)
2
2
-(4-(Cyclopentyloxy)benzylidene)cyclopentanone (5a)
A mixture of 4-(cyclopentyloxy)benzaldehyde 3 (0.57 g, 0.003 mol),
ethylacetoacetate (0.39 g, 0.003 mol), malononitrile (0.20 g,
ꢁ
Crystallisation solvent, ethanol; Yield, 55%; mp: 282–283 C; IR
À1
1
(
KBr) ꢀmax/cm 1600 (C ¼ O), 1535, 1520, 1510, 1500 (C ¼ C).
H
0.003 mol), and sodium benzoate (15 mol%) in ethanol (20 ml) was
NMR (DMSO-d ); d: 7.55 (d, 2H, Ar-H, J ¼ 8 Hz), 7.11 (brs, 1H, CH¼),
6
stirred at room temperature for 24 h. The reaction mixture was fil-
tered, and the solid product was washed with water and then
with ethanol, dried and crystallised from dimethylformamide.
6
CH
.90 (d, 2H, Ar-H, J ¼ 8 Hz), 4.89–4.80 (m, 1H, CH), 3.20–3.10 (m, 2H,
2
), 2.11–1.88 (m, 4H, 2CH
2
), 1.72–1.61 (m, 4H, 2CH
2
), 1.60–1.45
þ
þ
À1
ꢁ
(m, 4H, 2CH
2
). MS m/z (%); 257.08 (0.98, M þ1), 256.09 (1.28, M ), Yield, 45%; mp >300 C; IR (KBr) ꢀmax/cm 3401 and 3326 (NH2),
1
1
1
7
46.05 (54.79), 145.04 (35.70), 131.03 (100.00), 117.06 (25.47), 2221 (CꢂN), 1697 (C ¼ O). H NMR (DMSO-d ); d: 8.30 (brs, 2H,
6
15.03 (38.21), 107.02 (73.33). Anal. Calcd. for C17
H
20
O
2
(%): C, NH , D O exchangeable), 7.30 (d, 2H, Ar-H, J ¼ 8 Hz), 7.90 (d, 2H,
2
2
9.65; H, 7.86. Found: C, 80.05; H, 8.06.
Ar-H, J ¼ 8 Hz), 5.70 (s,1H, 4-H of pyran), 5.10–5.00 (m, 1H, CH),