Molecules 2020, 25, 1697
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plates (60F-254) using ultraviolet light as the visualizing agent. NMR spectra were recorded on a Varian
Inova 400 spectrometer (Varian, Palo Alto, CA, USA) and were calibrated using residual undeuterated
1
solvent as an internal reference (CDCl3: H NMR = 7.26, 13C NMR = 77.16). The following abbreviations
or combinations thereof have been used to explain the multiplicities observed: s = singlet, d = doublet,
t = triplet, q = quartet, m = multiplet, br = broad. Liquid chromatography (LC) and high-resolution
mass spectra (HRMS) were recorded on a ThermoFisher hybrid LTQ FT (ICR 7T) (ThermoFisher,
Waltham, MA, USA). The University of Southampton (Southampton, UK) small molecule X-ray facility
collected and analyzed all X-ray diffraction data. Compounds 10 and 11 were prepared as previously
4-(dimethylamino)-N-methyl-3-nitrobenzene-1-sulfonamide (12) was obtained as a yellow solid (465 mg,
1.793 mmol, 84%). MP 132–134 ◦C; 1H NMR (400 MHz, DMSO-d6)
δ 8.09 (d, J = 2.3 Hz, 1H), 7.75 (dd, J
= 9.1, 2.3 Hz, 1H), 7.32 (d, J = 9.1 Hz, 1H), 2.93 (s, 6H), 2.40 (s, 3H). HRMS m/z [M + H]+ calculated
for C9H14N3O4S: 260.0705, found 260.0696, LC tR = 4.00 min, >98% purity, consistent with previously
3-amino-4-(dimethylamino)-N-methylbenzene-1-sulfonamide (13) was obtained as a purple solid (442 mg,
1.928 mmol, 100%). MP 66–68 ◦C; 1H NMR (400 MHz, DMSO-d6)
δ 7.15–7.04 (m, 2H), 7.00 (d, J =
8.2 Hz, 1H), 6.93 (dd, J = 8.2, 2.2 Hz, 1H), 5.14 (s, 2H), 2.61 (s, 6H), 2.38 (d, J = 5.0 Hz, 3H). HRMS
m/z [M + H]+ calculated for C9H16N3O2S: 230.0963, found 230.0956, LC tR = 2.77 min, >98% purity
consistent with previously reported results [8].
3-((6,7-dimethoxyquinazolin-4-yl)amino)-4-(dimethylamino)-N-methylbenzenesulfonamide (7) was obtained
as a yellow solid (98.5 mg, 0.236 mmol, 53%). MP 244–246 ◦C; 1H NMR (400 MHz, DMSO-d6) δ 11.46
(s, 1H), 8.75 (s, 1H), 8.34 (s, 1H), 7.70–7.55 (m, 2H), 7.40 (s, 1H), 7.32 (q, J = 5.0 Hz, 1H), 7.22–7.15 (m,
1H), 3.98 (s, 6H), 2.79 (s, 6H), 2.40 (d, J = 5.0 Hz, 3H). 13C NMR (100 MHz, DMSO-d6)
δ 159.0, 156.4,
151.9, 150.3, 148.8, 135.4, 129.2, 128.6, 126.8, 125.9, 117.7, 107.2, 103.9, 99.7, 56.9, 56.5, 42.2 (2C, s), 28.7.
HRMS m/z [M + H]+ calculated for C19H24N5O4S: 418.1549, found 418.1540, LC tR = 3.04 min, >98%
purity consistent with previously reported results [10].
3-((6,7-dimethoxy-2-methylquinazolin-4-yl)amino)-4-(dimethylamino)-N-methylbenzenesulfonamide (15) was
obtained as a yellow solid (101 mg, 0.235 mmol, 56%). MP 252-254 ◦C; 1H NMR (400 MHz, DMSO-d6)
δ
11.23 (s, 1H), 8.28 (s, 1H), 7.67 (d, J = 2.3 Hz, 1H), 7.63 (dd, J = 8.7, 2.3 Hz, 1H), 7.39 (s, 1H), 7.32 (q, J =
5.0 Hz, 1H), 7.21 (d, J = 8.8 Hz, 1H), 3.98 (s, 6H), 2.80 (s, 6H), 2.52 (s, 3H), 2.44 (d, J = 5.0 Hz, 3H). 13
C
NMR (100 MHz, DMSO-d6)
δ 159.0, 158.4, 156.2, 151.6, 149.7, 136.0, 129.0, 128.5, 126.5, 125.9, 117.8,
105.7, 103.8, 99.1, 56.8, 56.4, 42.0 (2C, s), 28.7, 21.9. HRMS m/z [M + H]+ calculated for C20H26N5O4S:
432.1706, found 432.1700, LC tR = 3.25 min, >98% purity.
4-(dimethylamino)-3-((6-methoxyquinazolin-4-yl)amino)-N-methylbenzenesulfonamide (16) was obtained as a
yellow solid (127 mg, 0.387 mmol, 64%). MP 224–226 ◦C; 1H NMR (400 MHz, DMSO-d6)
δ 11.60 (s,
1H), 8.81 (s, 1H), 8.35 (d, J = 2.6 Hz, 1H), 7.94 (d, J = 9.2 Hz, 1H), 7.76 (dd, J = 9.2, 2.6 Hz, 1H), 7.68 (d, J
= 2.2 Hz, 1H), 7.65 (dd, J = 8.6, 2.3 Hz, 1H), 7.33 (q, J = 5.0 Hz, 1H), 7.22 (d, J = 8.7 Hz, 1H), 3.98 (s, 3H),
2.82 (s, 6H), 2.43 (d, J = 4.9 Hz, 3H). 13C NMR (100 MHz, DMSO-d6)
δ 159.9, 159.1, 151.8, 149.1, 133.6,
129.3, 128.5, 127.0, 126.9, 125.7, 121.7, 117.8, 114.6, 104.3, 56.6, 42.2 (2C, s), 28.7. HRMS m/z [M + H]+
calculated for C18H22N5O3S: 388.1443, found 388.1434, LC tR = 3.08 min, >98% purity consistent with
previously reported results [10].
4-(dimethylamino)-3-((7-methoxyquinazolin-4-yl)amino)-N-methylbenzenesulfonamide (17) was obtained as a
mustard solid (133 mg, 0.344 mmol, 67%). MP 216–219 ◦C; 1H NMR (400 MHz, DMSO-d6)
δ 11.69 (s,
1H), 8.86 (d, J = 9.2 Hz, 1H), 8.82 (s, 1H), 7.73–7.57 (m, 2H), 7.49 (dd, J = 9.3, 2.5 Hz, 1H), 7.42 (d, J =
2.5 Hz, 1H), 7.36 (q, J = 5.1 Hz, 1H), 7.23–7.18 (m, 1H), 3.98 (s, 3H), 2.80 (s, 6H), 2.42 (d, J = 4.5 Hz,
3H).13C NMR (100 MHz, DMSO-d6)
δ 164.9, 159.9, 151.8, 150.9, 140.8, 129.3, 128.5, 127.0, 126.9, 125.8,
119.2, 117.9, 107.2, 100.2, 56.4, 42.2 (2C, s), 28.7. HRMS m/z [M + H]+ calculated for C18H22N5O3S:
388.1443, found 388.1436, LC tR = 3.07 min, >98% purity.