Q. Ji et al. / European Journal of Medicinal Chemistry 108 (2016) 166e176
173
H), 7.29 (t, J ¼ 7.9 Hz, 2H, coumarin-6-H, benzene-H), 7.15 (t,
J ¼ 8.9 Hz, 3H, benzene-H), 7.10 (t, J ¼ 7.7 Hz, 1H, benzene-H), 5.70
(s, 1H, coumarin-3-H), 4.41 (m, J ¼ 12.2, 6.2 Hz, 2H, CH2), 3.87 (dd,
J ¼ 11.8, 6.1 Hz, 1H, NHCH2), 3.75 (dd, J ¼ 10.6, 6.2 Hz, 1H, NHCH2),
3.72 (s, 3H, OCH3), 3.66 (dd, J ¼ 13.2, 5.5 Hz, 2H, CH2), 2.99 (s, 3H,
NCH3), 2.45 (s, 3H, CH3), 2.07 (s, 1H, NH). 13C NMR (150 MHz, CDCl3)
CDCl3)
461.1472, found, 461.1473.
d
2.42e2.62. HRMS: calcd for C22H25N2O7P [MþH]þ,
4.6.7. Methyl 2-((2-(methyl(8-methyl-2-oxo-2H-chromen-4-yl)
amino)ethoxy) (phenoxy)phosphorylamino) propanoate (7g)
Yellow oil; yield, 45%.1H NMR (600 MHz, CDCl3)
d 7.56e7.51 (t,
d
170.80, 162.77, 161.25, 152.36, 150.45, 142.26, 129.71, 127.35,
1H, coumarin-6-H), 7.34 (d, J ¼ 7.3 Hz, 1H, coumarin-5-H), 7.29 (d,
J ¼ 7.8, 2.4 Hz, 2H, coumarin-7-H, benzene-2-H), 7.16 (d, J ¼ 8.6 Hz,
1H, benzene-6-H), 7.13 (t, J ¼ 7.0 Hz, 2H, benzene-3,5-H), 7.10 (t,
J ¼ 7.8, 2.3 Hz, 1H, benzene-4-H), 5.68 (d, J ¼ 10.0 Hz, 1H, coumarin-
3-H), 4.42e4.30 (m, 2H, CH2), 4.04e3.93 (m, 1H, CH), 3.68 (s, 3H,
OCH3), 3.63 (dd, J ¼ 12.3, 7.0 Hz, 2H, CH2), 3.57 (s, 1H, NH), 2.98 (d,
J ¼ 11.8 Hz, 3H, NCH3), 2.45 (s, 3H, CH3), 1.34 (dd, J ¼ 18.2, 7.1 Hz, 3H,
125.89, 124.43, 121.66, 120.06, 115.69, 96.21, 63.57, 54.11, 52.38,
42.77, 39.69, 21.29. 31P NMR (243 MHz, CDCl3)
d 2.44e2.68. HRMS:
calcd for C22H25N2O7P [MþH]þ, 461.1472, found, 461.1471.
4.6.3. Methyl 2-((2-(methyl(7-methyl-2-oxo-2H-chromen-4-yl)
amino)ethoxy) (phenoxy) phosphorylamino)- acetate (7c)
Yellow oil; yield, 48%.1H NMR (600 MHz, CDCl3)
d 7.58 (d,
CHCH3). 13C NMR (150 MHz, CDCl3)
d 173.74, 162.54, 160.80, 152.79,
J ¼ 8.3 Hz,1H, coumarin-5-H), 7.28 (dd, J ¼ 9.4, 6.4 Hz, 2H, benzene-
H), 7.18e7.10 (m, 4H, benzene-H, coumarin-8-H), 7.00 (d, J ¼ 8.2 Hz,
1H, coumarin-6-H), 5.60 (s, 1H, coumarin-3-H), 4.40 (m, 2H, CH2),
3.78e3.73 (m, 2H, NHCH2), 3.71 (s, 3H, OCH3), 3.68e3.62 (m, 2H,
CH2), 2.99 (s, 3H, NCH3), 2.41 (s, 3H, CH3), 2.05 (s, 1H, NH). 13C NMR
150.56, 131.98, 129.67, 127.44, 125.36, 121.77, 120.01, 118.45, 115.88,
96.31, 63.39, 54.05, 52.41, 50.17, 39.68, 20.85, 16.77. 31P NMR
(243 MHz, CDCl3)d 2.47e2.65. HRMS: calcd for C23H27N2O7P
[MþH]þ, 475.1629, found, 475.1633.
(150 MHz, CDCl3)d 170.81, 162.65, 161.35, 152.53, 150.47, 132.66,
4.6.8. Methyl 2-((2-(methyl(7-methyl-2-oxo-2H-chromen-4-yl)
129.70, 127.16, 125.10, 122.92, 122.83, 120.04, 115.95, 96.25, 63.55,
amino)ethoxy) (phenoxy)phosphorylamino) propanoate (7h)
54.15, 52.38, 42.76, 39.74, 15.95. 31P NMR (243 MHz, CDCl3)
Yellow oil; yield, 37%.1H NMR (600 MHz, CDCl3)
d 7.57 (dd,
d
2.45e2.69. HRMS: calcd for C22H25N2O7P [MþH]þ, 461.1472,
J ¼ 11.4, 8.3 Hz, 1H, coumarin-5-H), 7.31e7.24 (m, 2H, coumarin-6-
H, benzene-H), 7.19e7.09 (m, 4H, benzene-H), 7.00 (d, J ¼ 8.2 Hz,
1H, coumarin-8-H), 5.61 (d, J ¼ 11.2 Hz, 1H, coumarin-3-H),
4.42e4.31 (m, 2H, CH2), 3.98 (dd, J ¼ 19.2, 8.4 Hz, 1H, CH), 3.85 (d,
J ¼ 10.5 Hz, 1H, NH), 3.68 (s, 3H, OCH3), 3.63 (t, J ¼ 5.4 Hz, 2H, CH2),
2.99 (d, J ¼ 12.8 Hz, 3H, NCH3), 2.42 (s, 3H, CH3), 1.35 (dd, J ¼ 15.3,
found, 461.1474.
4.6.4. Methyl 2-((2-(methyl(6-methyl-2-oxo-2H-chromen-4-yl)
amino)ethoxy) (phenoxy) phosphorylamino) acetate (7d)
Yellow oil; yield, 42%.1H NMR (600 MHz, CDCl3)
d 7.49 (s, 1H,
coumarin-5-H), 7.30e7.23 (m, 3H, coumarin-7-H, benzene-H), 7.19
(d, J ¼ 8.4 Hz, 1H, coumarin-8-H), 7.16e7.08 (m, 3H, benzene-H),
5.64 (s, 1H, coumarin-3-H), 4.40 (d, J ¼ 5.0 Hz, 2H, CH2), 3.94 (d,
J ¼ 5.3 Hz, 1H, NHCH2), 3.74 (d, J ¼ 6.1 Hz, 2H, NHCH2), 3.68 (s, 3H,
OCH3), 3.66 (d, J ¼ 4.9 Hz, 2H, CH2), 2.98 (s, 3H, NCH3), 2.37 (s, 3H,
CH3), 2.03 (d, J ¼ 2.9 Hz, 1H, NH). 13C NMR (150 MHz, CDCl3)
6.8 Hz, 3H, CHCH3). 13C NMR (150 MHz, CDCl3)
d 173.77, 162.48,
160.69, 152.56, 150.59, 142.25, 129.62, 125.41, 124.40, 121.59, 120.04,
117.46, 115.67, 96.48, 63.29, 54.10, 52.36, 50.17, 39.62, 21.55, 20.21.
31P NMR (243 MHz, CDCl3)
C
d 2.47e2.68. HRMS: calcd for
23H27N2O7P [MþH]þ, 475.1629, found, 475.1630.
d
170.80, 162.78, 161.46, 152.29, 150.45, 135.59, 132.15, 129.70,
4.6.9. Methyl 2-((2-(methyl(6-methyl-2-oxo-2H-chromen-4-yl)
127.09, 121.79, 120.05, 117.16, 115.56, 96.18, 63.58, 54.26, 52.38,
42.79, 39.68, 21.68. 31P NMR (243 MHz, CDCl3)
d 2.45e2.69. HRMS:
amino)ethoxy) (phenoxy)phosphorylamino) propanoate (7i)
Yellow oil; yield, 46%.1H NMR (600 MHz, CDCl3)
d 7.49 (d,
calcd for C22H25N2O7P [MþH]þ, 461.1472, found, 461.1474.
J ¼ 9.1 Hz, 1H, coumarin-8-H), 7.29e7.25 (m, 3H, coumarin-5-H,
benzene-H), 7.21 (d, J ¼ 8.4 Hz, 1H, coumarin-7-H), 7.18e7.09 (m,
3H, benzene-H), 5.66 (d, J ¼ 9.6 Hz, 1H, coumarin-3-H), 4.41e4.30
(m, 2H, CH2), 4.04e3.93 (m, 1H, CH), 3.86e3.76 (t, J ¼ 10.3 Hz, 1H,
NH), 3.67 (s, 3H, OCH3), 3.64 (t, J ¼ 5.4 Hz, 1H, CH2), 2.99 (d,
J ¼ 11.4 Hz, 3H, NCH3), 2.38 (s, 3H, CH3), 1.33 (dd, J ¼ 17.6, 7.1 Hz, 3H,
4.6.5. Methyl 2-((2-(methyl(6-tert-buty-2-oxo-2H-chromen-4-yl)
amino)ethoxy) (phenoxy) phosphorylamino) acetate (7e)
Yellow oil; yield, 47%.1H NMR (600 MHz, CDCl3)
d 7.67 (s, 1H,
coumarin-5-H), 7.54 (d, J ¼ 8.7 Hz, 1H, coumarin-7-H), 7.27 (dd,
J ¼ 8.2, 5.5 Hz, 3H, coumarin-8-H, benzene-H), 7.17e7.11 (m, 3H,
benzene-H), 5.68 (s, 1H, coumarin-3-H), 4.43 (dd, J ¼ 12.2, 5.8 Hz,
2H, CH2), 3.76e3.73 (m, 2H, NHCH2), 3.71 (s, 3H, OCH3), 3.70 (d,
J ¼ 5.0 Hz, 2H, CH2), 3.03 (s, 3H, NCH3), 2.05 (s, 1H, NH), 1.35 (s, 9H,
CHCH3). 13C NMR (150 MHz, CDCl3)
d 173.76, 162.66, 160.84, 152.33,
150.55, 132.91, 132.40, 129.66, 125.04, 121.69, 120.02, 117.56, 115.90,
96.37, 63.41, 54.03, 52.44, 50.18, 39.70, 20.77, 21.02. 31P NMR
C(CH3)3).13C NMR (150 MHz, CDCl3)
d 170.79, 162.84, 161.14, 152.19,
(243 MHz, CDCl3)
d 2.46e2.69. HRMS: calcd for C23H27N2O7P
[MþH]þ, 475.1629, found, 475.1633.
150.42, 146.31, 129.70, 129.04, 125.10, 121.47, 120.01, 117.39, 115.43,
96.16, 63.59, 54.03, 52.38, 42.78, 39.66, 34.62, 31.37. 31P NMR
(243 MHz, CDCl3)
d
2.44e2.62. HRMS: calcd for C25H31N2O7P
4.6.10. Methyl 2-((2-(methyl(6-tert-buty-2-oxo-2H-chromen-4-yl)
[MþH]þ, 503.1942, found, 503.1944.
amino)ethoxy) (phenoxy) phosphorylamino) propanoate (7j)
Yellow oil; yield, 39%.1H NMR (600 MHz, CDCl3)
d 7.65 (dd,
4.6.6. Methyl 2-((2-(methyl(2-oxo-2H-chromen-4-yl)amino)
J ¼ 7.3, 2.2 Hz, 1H, coumarin-5-H), 7.53 (dd, J ¼ 8.7, 1.1 Hz, 1H,
coumarin-7-H), 7.33e7.23 (m, 3H, coumarin-8-H, benzene-H),
7.19e7.09 (m, 3H, benzene-H), 5.66 (d, J ¼ 9.9 Hz, 1H, coumarin-
3-H), 4.45e4.31 (m, 2H, CH2), 4.02e3.93 (m, 1H, CH), 3.76 (t,
J ¼ 10.2 Hz, 1H, NH), 3.69 (d, J ¼ 5.0 Hz, 1H, CH2), 3.67 (s, 3H, OCH3),
3.65 (d, J ¼ 6.5 Hz, 1H, CH2), 3.01 (d, J ¼ 11.3 Hz, 3H, NCH3), 1.35 (s,
10H, C(CH3)3, CHCH3), 1.32 (d, J ¼ 7.1 Hz, 2H, CHCH3). 13C NMR
ethoxy) (phenoxy)phosphorylamino)propanoate (7f)
Yellow oil; yield, 70%.1H NMR (600 MHz, CDCl3)
d 7.69 (dd,
J ¼ 12.0, 8.2 Hz,1H, coumarin-5-H), 7.47 (t, J ¼ 7.7 Hz,1H, coumarin-
7-H), 7.31 (d, J ¼ 8.3 Hz, 1H, coumarin-6-H), 7.28 (t, J ¼ 4.6 Hz, 1H,
coumarin-8-H), 7.22e7.07 (m, 5H, benzene-H), 5.65 (d, J ¼ 11.2 Hz,
1H, coumarin-3-H), 4.42e4.30 (m, 2H, CH2), 4.04e3.91 (m, 1H, CH),
3.92e3.72 (m, 1H, NH)3.67 (s, 3H, OCH3), 3.66e3.60 (m, 2H, CH2),
2.98 (d, J ¼ 13.1 Hz, 3H, NCH3), 1.33 (dd, J ¼ 13.3, 7.0 Hz, 3H,
(150 MHz, CDCl3)
d 173.71, 162.69, 160.74, 152.56, 150.49, 145.26,
129.68, 125.16, 123.40, 121.21, 120.04, 116.98, 115.58, 96.43, 63.52,
CHCH3).13C NMR (150 MHz, CDCl3)
d 173.79, 162.35, 160.71, 154.24,
54.09, 52.52, 50.21, 39.59, 31.25, 21.85. 31P NMR (243 MHz, CDCl3)
150.60, 131.37, 129.66, 125.29, 124.99, 123.26, 120.06, 117.81, 116.24,
d
2.47e2.70. HRMS: calcd for C26H33N2O7P [MþH]þ, 517.2098,
96.25, 63.36, 54.01, 52.42, 50.19, 39.64, 20.80. 31P NMR (243 MHz,
found, 517.2104.