Y. Tian et al. / European Journal of Medicinal Chemistry 85 (2014) 1e15
13
1H), 8.03 (d, J ¼ 7.8 Hz, 2H), 7.78 (d, J ¼ 7.5 Hz, 2H), 7.62 (d,
J ¼ 8.1 Hz, 2H), 7.29 (d, J ¼ 8.1 Hz, 2H), 3.92 (m, 2H), 3.55 (s, 2H), 2.65
2H), 7.28 (d, J ¼ 7.5 Hz, 2H), 3.94 (m, 2H), 3.66 (s, 2H), 2.66 (m, 2H),
1.94 (m, 2H); 13C NMR (150 MHz, DMSO)
167.10, 160.27, 141.75,
141.28, 135.90, 135.64, 128.91, 128.71, 128.33, 128.28, 125.85, 125.37,
d
(m, 2H), 1.85 (m, 2H); 13C NMR (150 MHz, DMSO)
d
159.79, 141.14,
140.95, 135.17, 135.01, 128.96, 128.27, 127.50, 125.40, 125.18, 64.69,
60.90, 59.03, 32.79, 27.73; ESI-HRMS m/z calcd For C20H23ClN2O6P
[MþH]þ 453.0977, found 453.0975.
64.39, 60.99, 59.26, 33.23, 28.16; ESI-HRMS m/z calcd For
C
21H23N3O6P [MþH]þ 444.1319, found 444.1312.
4.2.16.11. 2-Amino-4-(4-(2-(furan-2-yl)oxazol-4-yl)phenyl)-2-
4.2.16.5. 2-Amino-2-(hydroxymethyl)-4-(4-(2-(4-(trifluoromethyl)
phenyl)oxazol-4-yl)phenyl) butyl dihydrogen phosphate (20e).
Yield: 83.3%; White solid; Mp: 247e249 ꢀC; 1H NMR (300 MHz,
(hydroxymethyl)butyl dihydrogen phosphate (20k). Yield: 71.4%;
White solid; Mp: 235e237 ꢀC; 1H NMR (300 MHz, CD3OD)
d8.24 (s,
1H), 7.72 (m, 3H), 7.30 (d, J ¼ 8.1 Hz, 2H), 7.13 (s, 1H), 6.62 (s, 1H),
DMSO)
7.81 (d, J ¼ 7.5 Hz, 2H), 7.31 (d, J ¼ 7.5 Hz, 2H), 3.94 (m, 2H), 3.56 (s,
2H), 2.64 (m, 2H), 1.86 (m, 2H); 13C NMR (150 MHz, DMSO)
159.51,
d
8.77 (s, 1H), 8.24 (d, J ¼ 7.2 Hz, 2H), 7.93 (d, J ¼ 7.8 Hz, 2H),
3.98 (m, 2H), 3.69 (s, 2H), 2.68 (m, 2H), 1.97 (m, 2H); 13C NMR
(151 MHz, CD3OD)
d 154.93, 145.08, 142.43, 141.39, 133.68, 128.49,
d
125.51, 111.89, 111.71, 110.00, 64.37, 61.08, 59.94, 33.26, 28.43; ESI-
141.47, 141.29, 136.08, 130.42, 130.21, 130.16, 130.01, 128.64, 128.17,
126.70, 126.15, 126.13, 125.37, 124.73, 122.93, 64.79, 60.90, 59.02,
32.95, 27.89; ESI-HRMS m/z calcd For C21H23F3N2O6P [MþH]þ
487.1240, found 487.1238.
HRMS m/z calcd For
409.1152.
C
18H22N2O7P [MþH]þ 409.1159, found
4.2.16.12. 2-Amino-2-(hydroxymethyl)-4-(4-(2-(thiophen-2-yl)oxa-
zol-4-yl)phenyl)butyl dihydrogen phosphate (20l). Yield: 58.5%;
4.2.16.6. 2-Amino-2-(hydroxymethyl)-4-(4-(2-(4-(trifluoromethoxy)
phenyl)oxazol-4-yl)phenyl) butyl dihydrogen phosphate (20f).
Yield: 63.2%; White solid; Mp: 244e246 ꢀC; 1H NMR (400 MHz,
White solid; Mp: 240e242 ꢀC; 1H NMR (300 MHz, CD3OD)
d 8.18 (s,
1H), 7.71e7.68 (m, 3H), 7.59 (d, J ¼ 4.5 Hz, 1H), 7.28 (d, J ¼ 8.1 Hz,
2H), 7.14 (m, 1H), 3.96 (m, 2H), 3.67 (m, 2H), 2.70e2.67 (m, 2H),
DMSO)
7.57 (d, J ¼ 7.8 Hz, 2H), 7.32 (d, J ¼ 7.8 Hz, 2H), 3.91 (m, 2H), 3.57 (s,
2H), 2.67 (m, 2H), 1.86 (m, 2H); 13C NMR (150 MHz, DMSO)
159.77,
d
8.72 (s, 1H), 8.17 (d, J ¼ 8.1 Hz, 2H), 7.81 (d, J ¼ 8.1 Hz, 2H),
1.97e1.95 (m, 2H); 13C NMR (150 MHz, CD3OD)
d 158.29, 141.61,
141.29, 133.87, 133.54, 128.79, 128.67, 128.45, 128.02, 127.81, 125.47,
d
64.40, 61.15, 59.93, 33.33, 28.44; ESI-HRMS m/z calcd For
149.77, 141.44, 141.14, 135.68, 128.69, 128.39, 128.23, 125.87, 125.42,
121.65, 120.83, 119.12, 64.89, 60.99, 59.12, 33.05, 27.98; ESI-HRMS
m/z calcd For C21H23F3N2O7P [MþH]þ 503.1190, found 503.1194.
C
18H22N2O6PS [MþH]þ 425.0931, found 425.0927.
4.2.16.13. 2-Amino-2-(hydroxymethyl)-4-(4-(2-(4-methylbenzyl)
oxazol-4-yl)phenyl)butyl dihydrogen phosphate (20m). Yield: 40.0%;
4.2.16.7. 2-Amino-4-(4-(2-(4-ethylphenyl)oxazol-4-yl)phenyl)-2-
White solid; Mp: 221e223 ꢀC; 1H NMR (300 MHz, CD3OD)
d 8.06 (s,
(hydroxylmethyl)butyl dihydrogen phosphate (20g). Yield: 68.2%;
1H), 7.60 (d, J ¼ 7.8 Hz, 2H), 7.24 (d, J ¼ 7.8 Hz, 2H), 7.13 (d, J ¼ 8.1 Hz,
2H), 7.08 (d, J ¼ 8.4 Hz, 2H), 4.06 (s, 2H), 3.94 (m, 2H), 3.66 (s, 2H),
2.67e2.64 (m, 2H), 2.25 (s, 3H), 1.95 (m, 2H); 13C NMR (150 MHz,
White solid; Mp: 235e238 ꢀC; 1H NMR (300 MHz, DMSO)
d 8.62 (s,
1H), 7.95 (d, J ¼ 8.4 Hz, 2H), 7.78 (d, J ¼ 8.1 Hz, 2H), 7.39 (d,
J ¼ 8.1 Hz, 2H), 7.30 (d, J ¼ 7.8 Hz, 2H), 3.86 (m, 2H), 3.55 (s, 2H),
2.71e2.66 (m, 4H), 1.86 (m, 2H), 1.21 (t, J ¼ 7.5 Hz, 3H); 13C NMR
CD3OD)
d 166.03, 142.72, 142.01, 138.22, 125.89, 133.99, 130.67,
130.52, 130.13, 129.92, 127.03, 66.08, 62.78, 61.70, 35.06, 34.97,
(150 MHz, DMSO)
d
161.182, 146.90, 141.41, 140.93, 134.98, 128.75,
30.10, 21.36; ESI-HRMS m/z calcd For
447.1680, found 447.1669.
C
22H28N2O6P [MþH]þ
128.67, 126.22, 125.47, 124.46, 64.83, 61.07, 59.33, 33.19, 29.04,
28.16, 15.33; ESI-HRMS m/z calcd For
447.1679, found 447.1681.
C
22H28N2O6P [MþH]þ
4.2.16.14. 2-Amino-2-(hydroxymethyl)-4-(4-(2-(4-methoxybenzyl)
oxazol-4-yl)phenyl)butyl dihydrogen phosphate (20n). Yield: 55.6%;
4.2.16.8. 2-Amino-2-(hydroxymethyl)-4-(4-(2-(4-isopropylphenyl)
White solid; Mp: 223e225 ꢀC; 1H NMR (300 MHz, CD3OD)
d 8.06 (s,
oxazol-4-yl)phenyl)butyl dihydrogen phosphate (20h). Yield: 38.5%;
1H), 7.60 (d, J ¼ 7.8 Hz, 2H), 7.25 (d, J ¼ 7.8 Hz, 2H), 7.18 (d, J ¼ 8.1 Hz,
2H), 6.83 (d, J ¼ 8.4 Hz, 2H), 4.04 (s, 2H), 3.95 (m, 2H), 3.71 (s, 3H),
3.66 (s, 2H), 2.64 (m, 2H), 1.95 (m, 2H); 13C NMR (150 MHz, CD3OD)
White solid; Mp: 236e239 ꢀC; 1H NMR (300 MHz, DMSO)
d 8.20 (s,
1H), 7.96 (d, J ¼ 8.1 Hz, 2H), 7.71 (d, J ¼ 7.5 Hz, 2H), 7.35 (d, J ¼ 7.8 Hz,
2H), 7.29 (d, J ¼ 8.1 Hz, 2H), 3.96 (m, 2H), 3.67 (s, 2H), 2.93 (m, 1H),
2.70e2.67 (m, 2H), 1.97 (m, 2H), 1.25e1.23 (m, 6H); 13C NMR
d
166.21, 160.64, 142.72, 142.00, 135.87, 131.09, 130.55, 130.13,
128.97, 127.03, 115.48, 66.09, 62.79, 61.71, 55.99, 34.97, 34.64, 30.11;
ESI-HRMS m/z calcd For C22H28N2O7P [MþH]þ 463.1629, found
463.1618.
(150 MHz, CD3OD)
d 153.64, 143.27, 142.82, 135.54, 130.14, 129.15,
128.42, 128.10, 127.93, 127.19, 126.46, 66.05, 62.79, 61.66, 35.72,
35.00, 30.15, 24.46; ESI-HRMS m/z calcd For C23H30N2O6P [MþH]þ
461.1836, found 461.1835.
4.2.16.15. 2-Amino-4-(4-(2-(4-fluorobenzyl)oxazol-4-yl)phenyl)-2-
(hydroxylmethyl)butyl dihydrogen phosphate (20o). Yield: 43.5%;
4.2.16.9. 2-Amino-2-(hydroxymethyl)-4-(4-(2-(4-propylphenyl)oxa-
White solid; Mp: 225e228 ꢀC; 1H NMR (400 MHz, CD3OD)
d 8.07 (s,
zol-4-yl)phenyl)butyl dihydrogen phosphate (20h). Yield: 62.5%;
1H), 7.59 (d, J ¼ 8.0 Hz, 2H), 7.31e7.7.23 (m, 4H), 7.12e7.04 (m, 2H),
White solid; Mp: 235e237 ꢀC; 1H NMR (300 MHz, CD3OD)
d 8.20 (s,
4.16 (s, 2H), 3.96e3.93 (m, 2H), 3.66 (s, 2H), 2.69e2.62 (m, 2H),
1H), 7.94 (d, J ¼ 7.5 Hz, 2H), 7.70 (d, J ¼ 7.5 Hz, 2H), 7.28 (d, J ¼ 7.2 Hz,
4H), 3.95 (m, 2H), 3.66 (s, 2H), 2.63e2.61 (m, 4H), 1.97 (m, 2H),
1.65e1.62 (m, 2H), 0.91 (t, J ¼ 6.9 Hz, 3H); 13C NMR (150 MHz,
1.96e1.93 (m, 2H); 13C NMR (150 MHz, CD3OD)
d 164.69, 163.57,
161.62, 142.74, 142.17, 135.96, 132.53, 130.72, 130.49, 130.11, 127.05,
125.89, 116.80, 116.63, 66.08, 62.78, 61.69, 34.96, 30.10, 28.82; ESI-
CD3OD)
d
162.32, 145.78, 141.57, 141.12, 133.84, 129.02, 128.76,
HRMS m/z calcd For
451.1412.
C
21H25N2O6FP [MþH]þ 451.1410, found
128.43, 126.09, 125.49, 124.65, 64.38, 61.09, 59.95, 37.50, 33.29,
28.43, 24.12, 16.95; ESI-HRMS m/z calcd For C23H30N2O6P [MþH]þ
461.1836, found 461.1823.
4.2.16.16. 2-Amino-4-(4-(2-(4-chlorobenzyl)oxazol-4-yl)phenyl)-2-
(hydroxylmethyl)butyl dihydrogen phosphate (20p). Yield: 43.7%;
4.2.16.10. 2-Amino-4-(4-(2-(4-cyanophenyl)oxazol-4-yl)phenyl)-2-
White solid; Mp: 220e222 ꢀC; 1H NMR (300 MHz, CD3OD)
d 8.09 (s,
(hydroxylmethyl)butyl dihydrogen phosphate (20j). Yield: 58.8%;
1H), 7.61 (d, J ¼ 7.8 Hz, 2H), 7.28e7.24 (m, 6H), 4.12 (s, 2H), 3.95 (m,
White solid; Mp: 260e263 ꢀC; 1H NMR (300 MHz, CD3OD)
d
8.28 (s,
2H), 3.66 (s, 2H), 2.68e2.65 (m, 2H), 1.96e1.94 (m, 2H); 13C NMR
1H), 8.12 (d, J ¼ 7.8 Hz, 2H), 7.95 (d, J ¼ 8.1 Hz, 2H), 7.73 (d, J ¼ 7.2 Hz,
(150 MHz, CD3OD)
d 165.25, 142.78, 142.15, 136.04, 135.91, 134.40,