A. Venkanna et al. / European Journal of Medicinal Chemistry 163 (2019) 453e480
475
(
4
2 C), 123.67, 122.35, 121.87, 117.23, 116.65, 94.38, 56.16, 52.83,
9.52, 49.46, 32.86 ppm; ESI-MS: m/z ¼ 533 [MþH] .
5.1 Hz, 1H), 4.21 (dd, J ¼ 12.1, 6.9 Hz, 1H), 3.74 (dd, J ¼ 13.5, 8.0 Hz,
þ
13
1H), 3.26 (dd, J ¼ 13.5, 5.9 Hz, 1H), 3.23e3.13 (m, 1H); C NMR
3
(150 MHz, CDCl ) d 183.78, 169.20, 149.09, 143.51, 143.22, 138.41,
5.3.57. 3-Hydroxy-N-(4-(methoxymethoxy) phenyl)-2-(2-nitro-4-
136.00, 134.36, 130.79, 130.57, 130.07, 130.05, 129.90, 129.61, 129.58,
(
trifluoromethyl) benzyl)eN-phenylpropanamide (11p)
129.20, 129.17, 122.46, 122.44, 83.53, 64.10, 43.41, 32.16 ppm;
þ
HRMS-ESI (m/z): Calculated for C23
H
18
N
2
O
F
5 3
(MþH) : 459.1168,
Found: 459.1165.
5.3.60. Methyl 2-(2-fluoro-6-(trifluoromethyl) benzyl)-3-((4-
(methoxymethyl) phenyl) (phenyl) amino)-3-oxopropanoate (10q)
1H NMR (600 MHz, CDCl
)
d
8.22 (d, J ¼ 3.1 Hz, 1H), 7.84 (dd,
3
J ¼ 8.0, 1.3 Hz, 1H), 7.69 (t, J ¼ 7.4 Hz, 1H), 7.34e7.26 (m, 2H), 7.19 (t,
J ¼ 7.4 Hz, 1H), 7.12 (d, J ¼ 7.8 Hz, 1H), 7.00 (d, J ¼ 19.5 Hz, 2H), 6.85
(
(
1
1
m, 3H), 5.14 (d, J ¼ 15.4 Hz, 2H), 3.87 (d, J ¼ 10.9 Hz, 1H), 3.79e3.72
m, 1H), 3.45 (d, J ¼ 22.4 Hz, 4H), 3.36e3.28 (m, 1H), 3.27e3.21 (m,
13
1H NMR (600 MHz, CDCl
H), 2.88 (t, J ¼ 8.5 Hz, 1H); C NMR (150 MHz, CDCl
3
)
d
174.47,
3
)
d
7.42 (t, J ¼ 7.7 Hz, 1H), 7.32 (dd,
56.89, 155.74, 149.11, 141.83, 138.42, 134.65 (2 C), 129.86, 129.37,
J ¼ 34.3, 6.7 Hz, 2H), 7.20 (m, 5H), 6.97 (d, J ¼ 8.6 Hz, 1H), 6.92e6.73
128.22, 128.03, 127.49, 126.68, 126.15, 123.70, 122.40, 121.90, 117.28,
(m, 3H), 5.13 (s, 2H), 3.91 (t, J ¼ 7.2 Hz, 1H), 3.41 (d, J ¼ 6.2 Hz, 1H)
1
16.70, 94.41, 63.64, 56.13, 44.19, 32.85 ppm; ESI-MS: m/z ¼ 505
3.67 (s, 3H), 3.61e3.54 (m, 1H), 3.44 (d, J ¼ 7.7 Hz, 4H), 3.41 (d,
þ
13
[MþH] .
J ¼ 6.2 Hz, 1H); C NMR (150 MHz, CDCl
3
) d 169.58, 168.44, 162.85,
1
42.40, 142.08, 135.59, 129.79, 129.66, 128.84 (2 C), 128.52 (2 C),
5
.3.58. 3-Hydroxy-N-(4-hydroxyphenyl)-2-(2-nitro-4-
128.46, 127.36, 126.17, 125.93 (2 C), 122.17, 119.15, 119.00, 117.07,
94.32, 60.43, 52.59, 49.94, 25.34 ppm; ESI-MS: m/z ¼ 506 [MþH] .
þ
(
trifluoromethyl) benzyl)eN-phenylpropanamide (2p)
5.3.61. 2-(2-Fluoro-6-(trifluoromethyl) benzyl)-3-hydroxy-N-(4-
(methoxymethyl) phenyl)eN-phenylpropanamide (11q)
ꢀ
Yellow solid; 78% yield; M.P.:180.0e180.9 C; IR (neat): bs 3515,
2
7
8
960, 2927, 2854, 1678, 1637, 1538, 1392, 1355, 1325, 1136,
ꢁ1
1
33 cm
;
H NMR (600 MHz, MeOD)
d
8.31 (d, J ¼ 7.1 Hz, 1H),
1H NMR (600 MHz, CDCl
)
d
7.40 (t, J ¼ 8.1 Hz, 1H), 7.33 (m, 3H),
.05e8.01 (m, 1H), 7.66 (t, J ¼ 7.6 Hz, 1H), 7.30 (t, J ¼ 7.9 Hz, 1H), 7.24
3
(
m, 2H), 7.18 (t, J ¼ 7.4 Hz, 1H), 7.10 (d, J ¼ 7.5 Hz, 1H), 6.91 (d,
7.26e7.06 (m, 5H), 6.98 (d, J ¼ 8.7 Hz, 1H), 6.79 (d, J ¼ 44.8 Hz, 2H),
5.13 (q, J ¼ 6.9 Hz, 2H), 3.89 (m, 1H), 3.77 (d, J ¼ 10.8 Hz, 1H), 3.45 (d,
J ¼ 8.8 Hz, 1H), 6.76e6.53 (m, 3H), 3.89 (dd, J ¼ 10.6, 8.2 Hz, 1H),
3
3
1
1
.66 (dd, J ¼ 10.6, 5.6 Hz, 1H), 3.37e3.31 (m, 1H), 3.30e3.24 (m, 1H),
J ¼ 11.9 Hz, 3H), 3.43e3.35 (m,1H), 3.22 (bs,1H), 2.90 (d, J ¼ 14.3 Hz,
13
13
.08 (dd, J ¼ 12.7, 10.4 Hz, 1H); C NMR (150 MHz, MeOD)
58.61, 150.82, 144.26, 140.07, 135.77, 134.84, 130.67, 130.04, 129.11,
29.03, 127.74 (2 C), 125.46, 123.66, 123.42, 117.11, 116.66, 65.11,
d
175.71,
2H); C NMR (150 MHz, CDCl
3
)
d
174.60, 162.47, 142.17, 141.91,
135.50, 129.38, 129.22 (2 C), 128.62 (2 C), 128.16, 127.99, 172.241,
127.93, 125.87, 121.92, 118.89, 118.74, 116.67, 116.31, 94.03, 64.25,
55.70, 43.81, 25.55 ppm; ESI-MS: m/z ¼ 478 [MþH] .
þ
4
C
8.76, 48.61, 47.50, 33.83 ppm; HRMS-ESI (m/z): Calculated for
þ
H
23 19
N
2
O
5
F
3
(MþH) : 461.1324, Found: 461.1318.
5
.3.62. 2-(2-Fluoro-6-(trifluoromethyl) benzyl)-3-hydroxy-N-(4-
5.3.59. 3-(2-Nitro-4-(trifluoromethyl) benzyl)-5-phenyl-1-oxa-5-
hydroxyphenyl)eN-phenylpropanamide (2q)
azaspiro [5.5] undeca-7, 10-diene-4, 9-dione (1p)
ꢀ
White solid; 78% yield; M.P.:143.3e143.9 C; IR (neat): bs 3495,
ꢁ1
2
962, 2928, 2850, 1640, 1592, 1512, 1316, 1168, 1114, 833, 965 cm
;
1
Yellow liquid; purity 96.5%; 64% yield; IR (neat): 3331, 2946,
H NMR (600 MHz, MeOD) d 7.89 (s, 1H), 7.53e7.47 (m, 2H),
ꢁ
1
1
2
(
1
3
834, 1647, 1450, 1327, 1020, 916, 762, 696 cm
;
H NMR
7.43e7.39 (m, 1H), 7.31 (t, J ¼ 7.9 Hz, 2H), 7.24e7.14 (m, 4H), 7.03 (d,
J ¼ 8.8 Hz,1H), 6.73 (d, J ¼ 8.8 Hz,1H), 6.59 (s,1H), 3.93 (m, 1H), 3.54
(m, 1H), 3.27e3.21 (m, 1H), 3.20e3.13 (m, 1H), 2.83 (t, J ¼ 10.9 Hz,
600 MHz, CDCl
3
)
d
8.30 (d, J ¼ 0.9 Hz, 1H), 7.82 (dd, J ¼ 8.1, 1.5 Hz,
H), 7.77 (d, J ¼ 8.1 Hz, 1H), 7.37e7.31 (m, 3H), 7.09 (dd, J ¼ 10.3,
.2 Hz, 1H), 7.06e70.2 (m, 2H), 6.94 (d, J ¼ 3.2 Hz, 1H), 6.15 (dd,
1
3
1H); C NMR (150 MHz, MeOD)
d 175.88, 163.88, 158.01, 157.04,
J ¼ 10.3, 2.0 Hz, 1H), 6.09 (dd, J ¼ 10.2, 2.0 Hz, 1H), 4.43 (dd, J ¼ 12.1,
144.17, 134.77, 130.13, 129.71, 129.58 (2 C), 128.76, 128.35, 127.38