RCHH HARM
A P
Arch. Pharm. Chem. Life Sci. 2017, 350, e1700076
Chromen-2-ones as Cholinesterase Inhibitors
Archiv der Pharmazie
N-(3-(Dimethylamino)propyl)-2-((3-hexyl-4-methyl-2-oxo-
2H-chromen-7-yl)oxy)acetamide (31) [28]
2-diamine (1.37 g, 15.24 mmol) gave the title compound 33 as
a
white solid (0.87 g, 75%) by following the general
The reaction of ethyl 2-((3-hexyl-4-methyl-2-oxo-2H-chromen-
7-yl)oxy)acetate (19) (1 g, 2.88 mmol) with N1,N1-dimethyl-
propane-1,3-diamine (1.17 g, 11.52 mmol) gave the title
compound 31 as a white solid (0.93 g, 80%) by following
the general procedure; m.p.: 136.0–137.1°C; Rf: 0.47 (MeOH/
CHCl3 1:49); UV (MeOH) lmax: 318 nm; IR (KBr) nmax: 3373.96
procedure; m.p.: 116.5–117.4°C; Rf: 0.41 (MeOH/CHCl3 1:49);
UV (MeOH) lmax:272nm;IR(KBr)nmax: 3483.31 (N-H str), 3266.03,
–
2831.81, 1711.00 (C O), 1652.01 (NHCO-), 1573.45, 1552.15,
–
1431.37, 1246.74, 1168.79, 1060.91, 930.85, 837.95, 607.85,
548.75 cmꢂ1 1H NMR (400 MHz, CDCl3): d 2.20 (s, 6H, H-10000),
;
2.39 (s, 3H, C-40 CH3), 2.43 (t, 2H, J¼ 5.95 Hz, H-200), 3.38–3.43 (m,
2H, H-100), 4.52 (s, 2H, H-2), 6.29 (s, 1H, H-30), 7.04 (d, 1H,
J¼ 2.75 Hz, H-50), 7.08 (brs, 1H, NH), 7.14 (dd, 1H, J ¼ 2.75 and
9.16 Hz, H-70), 7.27 (d, 1H, J¼ 9.16 Hz, H-80) ppm; 13C NMR
(100.5 MHz, CDCl3): d 18.64 (C-40 CH3), 36.45 (C-100), 45.15 (C-10000),
57.78 (C-200), 68.02 (C-2), 108.77 (C-50), 115.78 (C-30), 118.27 (C-70),
119.46 (C-80), 120.55 (C-100), 148.54, 151.69, and 153.61 (C-40, C-60,
and C-90), 160.63 and 167.62 (C-20 and C-1) ppm; HRMS:
m/z [MþNa]þ calculated for C16H20N2O4: 327.1321. Found:
327.1331.
–
(N-H str), 2923.56, 1709.94 (C O), 1662.74 (NHCO-), 1618.85,
–
1550.06, 1430.12, 1285.53, 1162.34, 1090.23, 871.91, 780.88,
1
601.50 cmꢂ1; H NMR (400 MHz, CDCl3): d 0.88 (t, 3H, J ¼ 6.96
Hz, H-6000), 1.29–1.31 (m, 4H, H-4000 and H-5000), 1.36–1.41 (m, 2H,
H-3000), 1.47–1.54 (m, 2H, H-2000), 1.66–1.70 (m, 2H, H-200), 2.18 (s,
6H, H-10000), 2.38 (s, 3H, C-40 CH3), 2.39 (t, 2H, J ¼ 5.86 Hz, H-300),
2.62 (t, 2H, J ¼ 8.05 Hz, H-1000), 3.42–3.47 (m, 2H, H-100), 4.51 (s,
2H, H-2), 6.80 (d, 1H, J ¼ 2.20 Hz, H-80), 6.83 (dd, 1H, J ¼ 2.20
and 8.79 Hz, H-60), 7.53 (d, 1H, J ¼ 8.79 Hz, H-50), 8.33 (brs, 1H,
13
NH) ppm; C NMR (100.5 MHz, CDCl3): d 14.02 (C-6000), 14.79
(C-40 CH3), 22.56 (C-5000), 25.43 (C-200), 27.53, 28.70, 29.31, and
31.64 (C-1000–C-4000), 39.43 (C-100), 45.34 (C-10000), 58.86 (C-300),
67.46 (C-2), 102.15 (C-80), 111.06 (C-60), 115.30 (C-100), 124.57
(C-30), 125.73 (C-50), 145.56 (C-40), 153.43 and 159.06 (C-70 and
C-90), 161.74 and 167.08 (C-20 and C-1) ppm; HRMS: m/z
[MþNa]þ calculated for C23H34N2O4: 425.2416. Found:
425.2402.
N-(2-(Diethylamino)ethyl)-2-((4-methyl-2-oxo-2H-
chromen-6-yl)oxy)acetamide (34)
The reaction of ethyl 2-((4-methyl-2-oxo-2H-chromen-6-yl)-
oxy)acetate (20) (1 g, 3.81 mmol) with N1,N1-diethylethane-
1,2-diamine (1.77 g, 15.24 mmol) gave the title compound 34
as a light brown solid (1.13 g, 60%) by following the general
procedure; m.p.: 118–119°C; Rf: 0.45 (MeOH/CHCl3 1:49); UV
(MeOH) lmax: 273 nm; IR (KBr) nmax: 3299 (N-H str), 2975, 1716,
(C O), 1650 (NHCO-) cmꢂ1; 1H NMR (400 MHz, CDCl3): d 0.95 (t,
–
N-(3-(Diethylamino)propyl)-2-((3-hexyl-4-methyl-2-oxo-
2H-chromen-7-yl)oxy)acetamide (32) [28]
–
6H, J ¼ 7.3 Hz, H-20000), 2.39 (d, 3H, J ¼ 0.9 Hz, C-40 CH3), 2.48 (q,
4H, J ¼ 7.1 Hz, H-10000), 2.54 (t, 2H, J ¼ 5.9 Hz, H-200), 3.33–3.37
(m, 2H, H-100), 4.52 (s, 2H, H-2), 6.29 (d, 1H, J ¼ 0.9 Hz, H-30), 7.02
(d, 1H, J ¼ 2.7 Hz, H-50), 7.11 (dd, 1H, J ¼ 2.7 and 9.1 Hz, H-70),
7.24 (brs, 1H, NH), 7.27 (d, 1H, J ¼ 9.1 Hz, H-80) ppm; 13C NMR
(100.5 MHz, CDCl3): d 11.91 (C-20000), 18.60 (C-40 CH3), 36.55 (C-
100), 46.73 (C-10000), 51.24 (C-200), 67.91 (C-2), 108.48 (C-50), 115.74
(C-30), 118.31 (C-70), 119.32 (C-80), 120.54 (C-100), 148.50,
151.64, and 153.64 (C-40, C-60, and C-90), 160.61 and 167.42 (C-
20 and C-1) ppm; HRMS: m/z [MþH]þ calculated for
The reaction of ethyl 2-((3-hexyl-4-methyl-2-oxo-2H-chromen-
7-yl)oxy)acetate (19) (1 g, 2.88 mmol) with N1,N1-diethylpro-
pane-1,3-diamine (1.50 g, 11.52 mmol) gave the title com-
pound 32 as a white solid (1 g, 81%) by following the general
procedure; m.p.: 115.6–117.2°C; Rf: 0.48 (MeOH/CHCl3 1:49);
UV (MeOH) lmax: 319 nm; IR (KBr) nmax: 3370.84 (N-H str),
–
2922.59, 1710.76 (C O), 1662.03 (NHCO-), 1618.44, 1549.66,
–
1426.54, 1286.31, 1160.00, 1088.95, 781.66, 599.06 cmꢂ1
;
1H NMR (400 MHz, CDCl3): d 0.86 (t, 3H, J ¼ 6.87 Hz, H-6000),
0.98 (t, 6H, J ¼ 7.33 Hz, H-20000), 1.27–1.31 (m, 4H, H-4000 and H-
5000), 1.33–1.40 (m, 2H, H-3000), 1.45–1.53 (m, 2H, H-2000), 1.63–
1.69 (m, 2H, H-200), 2.36 (s, 3H, C-40 CH3), 2.47 (q, 4H, J ¼ 7.33 Hz,
H-10000), 2.51 (t, 2H, J ¼ 5.95 Hz, H-300), 2.61 (t, 2H, J ¼ 7.33 Hz,
H-1000), 3.42–3.46 (m, 2H, H-100), 4.49 (s, 2H, H-2), 6.79 (d, 1H,
J ¼ 2.29 Hz, H-80), 6.68 (dd, 1H, J ¼ 2.29 and 8.70 Hz, H-60), 7.52
(d, 1H, J ¼ 8.70 Hz, H-50), 8.47 (brs, 1H, NH) ppm; 13C NMR
(100.5 MHz, CDCl3): d 11.52 (C-20000), 14.04 (C-6000), 14.80 (C-40
CH3), 22.57 (C-5000), 25.19 (C-200), 27.53, 28.71, 29.31, and 31.65
(C-1000 C-4000), 39.82 (C-100), 46.95 (C-10000), 52.32 (C-300), 67.55 (C-
2), 102.26 (C-80), 111.04 (C-60), 115.30 (C-100), 124.56 (C-30),
125.73 (C-50), 145.59 (C-40), 153.41 and 159.03 (C-70 and C-90),
161.79 and 166.96 (C-20 and C-1) ppm; HRMS: m/z [MþNa]þ
calculated for C25H38N2O4: 453.2729. Found: 453.2729.
C
18H24N2O4: 333.1809. Found: 333.1805.
N-(3-(Dimethylamino)propyl)-2-((4-methyl-2-oxo-2H-
chromen-6-yl)oxy)acetamide (35) [28]
The reaction of ethyl 2-((4-methyl-2-oxo-2H-chromen-6-yl)-
oxy)acetate (20) (1 g, 3.81 mmol) with N1,N1-dimethylpro-
pane-1,3-diamine (1.55 g, 15.24 mmol) gave the title com-
pound 35 as a white solid (0.89 g, 73%) by following the
general procedure; m.p.: 119.7–118.8°C; Rf: 0.46 (MeOH/CHCl3
1:49); UV (MeOH) lmax: 272 nm; IR (KBr) nmax: 3467.99 (N-H str),
–
2815.93, 1715.96 (C O), 1648.52 (NHCO-), 1574.59, 1432.04,
–
1245.18, 1173.60, 1058.26, 929.85, 838.82, 610.28 cmꢂ1
;
1H NMR (400 MHz, CDCl3): d 1.63–1.69 (m, 2H, H-200), 2.15 (s,
6H, H-10000), 2.23 (t, 2H, J ¼ 6.40 Hz, H-300), 2.39 (d, 3H,
J ¼ 0.92 Hz, C-40 CH3), 3.39–3.44 (m, 2H, H-100), 4.49 (s, 2H, H-
2), 6.29 (d, 1H, J ¼ 0.92 Hz, H-30), 7.00 (d, 1H, J ¼ 2.75 Hz, H-50),
7.08 (dd, 1H, J ¼ 2.75 and 9.16 Hz, H-70), 7.27 (d, 1H, J ¼ 9.16 Hz,
H-80), 8.15 (brs, 1H, NH) ppm; 13C NMR (100.5 MHz, CDCl3): d
18.63 (C-40 CH3), 25.66 (C-200), 39.13 (C-100), 45.33 (C-10000), 58.55
N-(2-(Dimethylamino)ethyl)-2-((4-methyl-2-oxo-2H-
chromen-6-yl)oxy)acetamide (33) [28]
The reaction of ethyl 2-((4-methyl-2-oxo-2H-chromen-6-yl)-oxy)-
acetate (20) (1 g, 3.81 mmol) with N1,N1-dimethylethane-1,
ß Deutsche Pharmazeutische Gesellschaft
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