Pharmaceuticals 2021, 14, 412
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and NaH (60% dispersion in mineral oil) (80 mg (2.00 mmol)) in dry DMF (16 mL) gave the
raw carboxamide which was purified by recrystallization in CH2Cl2 to yield compound
◦
1
as white crystals (63 mg (17%)). m.P. 162 C. IR = 3198, 2981, 1665, 1591, 1531, 1500,
1394, 1377, 1325, 1277, 1260, 1218, 1142, 1042, 940, 862, 810; 1H NMR (DMSO-d6, 400 MHz)
δ
= 1.20 (t, J = 6.9 Hz, 3H, CH3), 1.32 (t, J = 6.9 Hz, 3H, CH3), 2.40 (s, 3H, ArCH3), 3.90
(q, J = 6.9 Hz, 2H, OCH2), 4.05 (q, J = 6.9 Hz, 2H, OCH2), 7.07 (d, J = 8.4 hz, 1H, 5”-H),
7.32-7.37 (m, 2H, 2”-H, 6”-H), 7.45 (t, J = 7.6, 1H, 5-H), 7.49 (d, J = 7.6 Hz, 1H, 4-H), 7.79
(br, d, J = 7.4 hz, 1H, 6-H), 7.82 (br, s, 1H, 2-H), 11.17 (br, 1H, NH); 13C NMR (DMSO-d6,
100 MHz) δ = 14.47 (CH3), 14.56 (CH3), 20.86 (ArCH3), 63.79 (2 OCH2), 111.68 (C-2”), 113.21
(C-5”), 116.92 (C-1”), 120.44 (C-6”), 125.17 (C-6), 128.52 (C-2), 128.61 (C-5), 132.22 (C-1),
133.41 (C-4), 138.13 (C-3), 148.10 (C-3”), 150.06 (C-3’), 150.33 (C-4”), 151.23 (C-4’), 166.78
(C=O); HRMS (EI+) calcd for C20H21N3O4: 367.1532; found: 367.1526.
N-(4-(3,4-Diethoxyphenyl)-1,2,5-oxadiazol-3-yl)benzamide (10): Method A: The reaction
of compound
9 (249 mg (1.00 mmol)), benzoyl chloride (183 mg (1.30 mmol)) and NaH
(60% dispersion in mineral oil) (80 mg (2.00 mmol)) in dry DMF (16 mL) gave the raw
carboxamide which was purified by recrystallization in CH2Cl2 to yield compound 10 as
◦
white crystals (81 mg (23%)). m.P. 199 C. IR = 3212, 2980, 1660, 1591, 1530, 1501, 1468,
1395, 1378, 1324, 1275, 1258, 1216, 1141, 1040, 916, 852, 811; 1H NMR (DMSO-d6, 400 MHz)
δ
= 1.19 (t, J = 6.9 Hz, 3H, CH3), 1.31 (t, J = 6.9 Hz, 3H, CH3), 3.88 (q, J = 7.0 Hz, 2H, OCH2),
4.05 (q, J = 6.9 Hz, 2H, OCH2), 7.07 (d, J = 8.4 hz, 1H, 5”-H), 7.31 (d, J = 1.7 Hz, 1H, 2”-H),
7.33 (dd, J = 8.4, 1.7 Hz, 1H, 6”-H), 7.58 (t, J = 7.4 hz, 2H, 3-H, 5-H), 7.68 (t, J = 7.4 hz, 1H,
4-H), 8.00 (d, J = 7.2 Hz, 2H, 2-H, 6-H), 11.24 (br s, 1H, NH); 13C NMR (DMSO-d6, 100 MHz)
δ
= 14.45 (CH3), 14.57 (CH3), 63.78 (2 OCH2), 111.65 (C-2”), 113.19 (C-5”), 116.87 (C-1”),
120.43 (C-6”), 128.05 (C-2, C-6), 128.74 (C-3, C-5), 132.10 (C-1), 132.91 (C-4), 148.11 (C-3”),
149.95 (C-3’), 150.36 (C-4”), 151.24 (C-4’), 166.66 (C=O); HRMS (EI+) calcd for C19H19N3O4:
353.1375; found: 353.1373.
N-(4-(3,4-Diethoxyphenyl)-1,2,5-oxadiazol-3-yl)-2-methylbenzamide (11): Method A:
The reaction of compound
9 (249 mg (1.00 mmol)), 2-methylbenzoyl chloride (201 mg
(1.30 mmol)) and NaH (60% dispersion in mineral oil) (80 mg (2.00 mmol)) in dry DMF
(16 mL) gave the raw carboxamide which was purified by recrystallization in CH2Cl2
◦
to yield compound 11 as white crystals (103 mg (28%)). m.P. 170 C. IR = 3214, 2983,
1663, 1591, 1503, 1395, 1377, 1324, 1259, 1216, 1142, 1042, 918, 854, 803, 741, 687, 657,
618; 1H NMR (DMSO-d6, 400 MHz)
δ = 1.28 (t, J = 7.0 Hz, 3H, CH3), 1.34 (t, J = 7.0 Hz,
3H, CH3), 2.34 (s, 3H, ArCH3), 3.99 (q, J = 7.0 Hz, 2H, OCH2), 4.08 (q, J = 7.0 Hz, 2H,
OCH2), 7.11 (d, J = 8.4 hz, 1H, 5”-H), 7.33–7.37 (m, 4H, 2”-H, 3-H, 5-H, 6”-H), 7.45 (t,
J = 7.3 Hz, 1H, 4-H), 7.65 (d, J = 7.3 Hz, 1H, 6H), 11.12 (br, 1H, NH); 13C NMR (DMSO-d6,
100 MHz)
113.13 (C-5”), 116.96 (C-1”), 120.67 (C-6”), 125.79 (C-5), 127.89 (C-6), 130.92 (C-4), 131.10
(C-3), 133.97 (C-1), 136.63 (C-2), 148.21 (C-3”), 149.83 (C-3 ), 150.34 (C-4”), 151.22 (C-4 ),
168.70 (C=O); HRMS (EI+) calcd for C19H21N3O4: 367.1532; found: 367.1526.
N-(4-(3,4-Diethoxyphenyl)-1,2,5-oxadiazol-3-yl)-2-(trifluoromethyl)benzamide (12): Method
A: The reaction of compound (249 mg (1.00 mmol)), 2-(trifluoromethyl)benzoyl chloride
δ = 14.61 (2 CH3), 19.56 (ArCH3), 63.84 (OCH2), 63.97 (OCH2), 112.06 (C-2”),
´
´
9
(271 mg (1.30 mmol)) and NaH (60% dispersion in mineral oil) (80 mg (2.00 mmol)) in
dry DMF (16 mL) gave the raw carboxamide which was purified by recry◦stallization in
methanol to yield compound 12 as white crystals (38 mg (9%)). m.P. 171 C. IR = 3209,
2983, 1676, 1604, 1531, 1494, 1397, 1377, 1316, 1277, 1217, 1177, 1129, 1043, 921, 854, 811,
1
772, 651, 617; H NMR (DMSO-d6, 400 MHz)
δ = 1.32 (t, J = 7.0 Hz, 3H, CH3), 1.34 (t,
J = 7.0 Hz, 3H, CH3), 4.05 (q, J = 7.0 Hz, 2H, OCH2), 4.09 (q, J = 7.0 Hz, 2H, OCH2), 7.13
(d, J = 8.2 Hz, 1H, 5”-H), 7.34 (d, J = 1.8 Hz, 1H, 2”-H), 7.36 (dd, J = 8.2, 1.8 Hz, 1H, 6”-H),
7.76-7.84 (m, 3H, 4-H, 5-H, 6-H), 7.89 (d, J = 8.2 Hz, 1H, 3-H), 11.46 (br, 1H, NH); 13C NMR
(DMSO-d6, 100 MHz)
δ = 14.61 (CH3), 14.64 (CH3), 63.84 (OCH2), 63.96 (OCH2), 112.37
(C-2”), 113.09 (C-5”), 116.52 (C-1”), 120.94 (C-6”), 123.52 (q, J = 274 hz, CF3), 126.25 (q,
J = 31.7 Hz, C-2), 126.71 (q, J = 4.9 Hz, C-3), 128.69 (C-6), 131.05 (C-4), 132.69 (C-5), 134.03