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PAPER
(d, J = 8.1 Hz, 2 H), 7.91–7.97 (m, 4 H), 8.09 (s, 2 H), 8.71 (s, 1 H),
9.46 (s, 1 H, NH), 9.87 (s, 1 H, NH).
130.6, 131.7, 132.8, 133.1, 133.7, 135.4, 137.0, 140.7, 140.9, 141.1,
142.2, 147.7, 148.8, 149.2, 156.1, 158.7.
13C NMR (50 MHz, DMSO-d6): δ = 112.8, 117.3, 117.9, 120.6,
120.8, 121.7, 123.4, 128.3, 128.8, 129.0, 129.7, 130.4, 132.0, 132.2,
132.5, 132.7, 133.1, 133.2, 136.6, 138.1, 138.3, 141.1, 142.4, 148.8,
155.6, 158.6.
Anal. Calcd for C32H20Cl2N6O4: C, 61.65; H, 3.23; N, 13.48. Found:
C, 61.14; H, 3.35; N, 13.39.
N2,N4-Bis(3-chlorophenyl)-6,8-bis[3-(trifluoromethyl)phe-
nyl]quinazoline-2,4-diamine (6k)
Yield: 0.14 g (75%); yellow powder; mp 141 °C.
Anal. Calcd for C32H20Cl4N4: C, 63.81; H, 3.35; N, 9.30. Found: C,
63.35; H, 3.43; N, 9.09.
1H NMR (200 MHz, DMSO-d6): δ = 6.89 (d, J = 7.5 Hz, 1 H), 7.10
(d, J = 8.1 Hz, 1 H), 7.16–7.23 (m, 1 H), 7.43 (d, J = 8.1 Hz, 1 H),
7.51 (d, J = 9.0 Hz, 1 H), 7.81–7.88 (m, 4 H), 7.93–7.95 (m, 3 H),
8.10–8.15 (m, 5 H), 8.82 (s, 1 H), 9.50 (s, 1 H, NH), 9.90 (s, 1 H,
NH).
13C NMR (50 MHz, DMSO-d6): δ = 112.9, 117.4, 118.0, 120.9,
121.8, 123.6, 124.7 (q, J = 271.9 Hz), 124.8 (q, J = 270.5 Hz), 125.2
(q, J = 3.7 Hz,), 126.0 (q, J = 3.7 Hz), 127.8, 127.9 (q, J = 31.5 Hz),
128.0 (q, J = 32.0 Hz), 129.7, 130.5, 131.1, 132.4, 132.6, 133.2,
133.3, 136.5, 141.0, 142.3, 143.4 (q, J = 1.1 Hz), 143.6 (q, J = 1.1
Hz), 149.3, 156.0, 158.7.
N2,N4-Bis(3-chlorophenyl)-6,8-di(naphthalen-2-yl)quinazoline-
2,4-diamine (6g)
Yield: 0.15 g (85%); yellow powder; mp 137 °C.
1H NMR (200 MHz, DMSO-d6): δ = 6.80 (d, J = 7.0 Hz, 1 H), 6.98
(t, J = 7.7 Hz, 1 H), 7.22 (d, J = 7.4 Hz, 1 H), 7.44–7.57 (m, 5 H),
7.74 (d, J = 7.4 Hz, 1 H), 7.96–8.02 (m, 8 H), 8.11–8.15 (m, 3 H),
8.26 (s, 1 H), 8.33 (s, 1 H), 8.49 (s, 1 H), 8.93 (s, 1 H), 9.47 (s, 1 H,
NH), 9.99 (s, 1 H, NH).
13C NMR (50 MHz, DMSO-d6): δ = 113.0, 117.2, 117.9, 120.6,
120.7, 121.0, 121.9, 123.5, 125.5, 126.1, 126.2, 126.4, 126.7, 127.4,
127.7, 127.8, 128.4, 128.7, 128.8, 129.0, 129.7, 130.4, 132.4, 132.5,
133.0, 133.1, 133.3, 133.6, 134.1, 136.9, 137.4, 138.0, 141.2, 142.4,
149.2, 155.6, 158.8.
Anal. Calcd for C34H20Cl2F6N4: C, 61.00; H, 3.01; N, 8.37. Found:
C, 61.33; H, 3.03; N, 8.23.
One-Pot Chemoselective Bis-SNAr and Bis-Suzuki–Miyaura
Reactions; Synthesis of Compounds 6l–t; General Procedure
A solution of 6,8-dibromo-2,4-dichloroquinazoline (4; 0.1 g, 0.28
mmol) and the respective amine (1.12 mmol, 4 equiv) in a mixture
of DME–EtOH (9:1, 5 mL) was heated under microwave irradiation
(cf. temperature in Table 3). After cooling, 4-fluorophenylboronic
acid (86 mg, 0.62 mmol, 2.2 equiv), PdCl2(PPh3)2 (10 mg, 14 μmol,
0.05 equiv), K2CO3 (0.23 g, 1.68 mmol, 6 equiv), and H2O (0.5 mL)
were introduced under argon. The mixture was heated at 100 °C un-
der microwave irradiation for 1 h. After cooling, H2O (80 mL) was
added and the solution was extracted with CH2Cl2 (3 × 60 mL). The
combined organic layers were washed with H2O (3 × 100 mL), dried
(Na2SO4), and evaporated. The crude product was purified by col-
umn chromatography [silica gel, PE–EtOAc (9:1), (8:2 for 6r and
6s)] and recrystallized from MeCN.
HRMS (ESI): m/z [M + H]+ calcd for C40H26Cl2N4: 633.1607;
found: 633.1606.
N2,N4-Bis(3-chlorophenyl)-6,8-bis(5-methylthiophen-2-yl)quin-
azoline-2,4-diamine (6h)
Yield: 0.12 g (76%); yellow powder; mp 147 °C.
1H NMR (200 MHz, DMSO-d6): δ = 2.50 (s, 6 H, 2 × CH3), 6.87 (s,
2 H), 6.97 (d, J = 8.6 Hz, 1 H), 7.18–7.28 (m, 2 H), 7.40–7.48 (m, 2
H), 7.59–7.63 (m, 2 H), 7.92 (s, 1 H), 8.00 (d, J = 8.2 Hz, 1 H), 8.10
(s, 1 H), 8.24 (s, 1 H), 8.45 (s, 1 H), 9.38 (s, 1 H, NH), 9.82 (s, 1 H,
NH).
13C NMR (50 MHz, DMSO-d6): δ = 15.2 (CH3), 15.3 (CH3), 113.0,
117.7, 118.2, 119.2, 121.2, 121.3, 122.1, 123.6, 124.2, 125.4, 127.0,
128.3, 128.6, 129.9, 130.4, 133.1, 133.2, 136.7, 139.4, 140.5, 141.0,
141.4, 142.0, 147.3, 155.5, 158.7.
6,8-Bis(4-fluorophenyl)-N2,N4-diphenylquinazoline-2,4-di-
amine (6l)
Yield: 0.1 g (71%); brown powder; mp 114 °C.
Anal. Calcd for C30H22Cl2N4S2: C, 62.82; H, 3.87; N, 9.77. Found:
C, 62.70; H, 3.79; N, 9.86.
1H NMR (200 MHz, DMSO-d6): δ = 6.88 (t, J = 6.7 Hz, 1 H), 7.10–
7.16 (m, 3 H), 7.35–7.48 (m, 6 H), 7.82–7.97 (m, 9 H), 8.70 (s, 1 H),
9.15 (s, 1 H, NH), 9.77 (s, 1 H, NH).
N2,N4-Bis(3-chlorophenyl)-6,8-di(pyridin-3-yl)quinazoline-2,4-
diamine (6i)
Yield: 0.12 g (80%); yellow powder; mp 247 °C.
13C NMR (50 MHz, DMSO-d6): δ = 112.8, 114.6 (d, J = 20.9 Hz),
115.9 (d, J = 21.2 Hz), 119.0, 120.4, 121.0, 122.6, 123.7, 128.3,
128.7, 129.0 (d, J = 8.1 Hz), 132.0, 132.6 (d, J = 7.3 Hz), 135.8 (d,
J = 3.3 Hz), 136.2 (d, J = 3.3 Hz), 136.4, 139.7, 141.1, 148.9, 156.0,
158.8, 161.8 (d, J = 243.7 Hz), 162.0 (d, J = 244.8 Hz).
HRMS (ESI): m/z [M + H]+ calcd for C32H22F2N4: 501.1885; found:
501.1884.
1H NMR (200 MHz, DMSO-d6): δ = 6.90 (d, J = 7.8 Hz, 1 H), 7.11–
7.23 (m, 2 H), 7.42–7.58 (m, 3 H), 7.66 (d, J = 7.8 Hz, 1 H), 7.95
(d, J = 8.9 Hz, 2 H), 8.08–8.23 (m, 3 H), 8.34 (d, J = 7.2 Hz, 1 H),
8.63 (br s, 2 H), 8.84 (s, 1 H), 8.91 (s, 1 H), 9.19 (s, 1 H), 9.50 (s, 1
H, NH), 9.90 (s, 1 H, NH).
13C NMR (50 MHz, DMSO-d6): δ = 112.9, 117.5, 118.1, 120.9,
121.4, 121.8, 123.2, 123.6, 124.0, 129.9, 130.5, 131.0, 132.5, 133.2,
134.4, 134.7, 134.8, 134.9, 137.9, 141.0, 142.3, 148.1, 148.4, 148.7,
149.3, 150.4, 155.9, 158.7.
N2,N4,6,8-Tetrakis(4-fluorophenyl)quinazoline-2,4-diamine
(6m)
Yield: 0.14 g (93%); brown powder; mp 230 °C.
HRMS (ESI): m/z [M + H]+ calcd for C30H20Cl2N6: 535.1199;
found: 535.1202.
1H NMR (200 MHz, DMSO-d6): δ = 6.96 (t, J = 8.8 Hz, 2 H), 7.22–
7.39 (m, 6 H), 7.77–7.83 (m, 4 H), 7.93–7.96 (m, 5 H), 8.67 (s, 1 H),
9.18 (s, 1 H, NH), 9.80 (s, 1 H, NH).
13C NMR (50 MHz, DMSO-d6): δ = 112.7, 114.6 (d, J = 21.2 Hz),
115.3 (d, J = 22.0 Hz), 115.9 (d, J = 21.2 Hz), 120.3, 120.5 (d, J =
7.3 Hz), 124.7 (d, J = 7.7 Hz), 129.0 (d, J = 8.1 Hz), 132.1, 132.5,
132.6 (d, J = 7.7 Hz), 135.7 (d, J = 3.3 Hz), 135.9 (d, J = 1.8 Hz),
136.2 (d, J = 3.3 Hz), 136.4, 137.4 (d, J = 1.8 Hz), 148.8, 155.9,
157.1 (d, J = 245.5 Hz), 158.9, 161.8 (d, J = 243.7 Hz), 162.0 (d,
J = 244.4 Hz), 163.5 (d, J = 243.0 Hz).
N2,N4-Bis(3-chlorophenyl)-6,8-bis(3-nitrophenyl)quinazoline-
2,4-diamine (6j)
Yield: 0.12 g (71%); yellow powder; mp 245 °C.
1H NMR (200 MHz, DMSO-d6): δ = 6.86 (d, J = 7.2 Hz, 1 H), 7.10
(t, J = 7.6 Hz, 1 H), 7.22 (d, J = 7.2 Hz, 1 H), 7.43–7.54 (m, 2 H),
7.82 (t, J = 7.2 Hz, 2 H), 7.96 (s, 1 H), 8.05–8.11 (m, 2 H), 8.22–
8.42 (m, 5 H), 8.66 (s, 1 H), 8.74 (s, 1 H), 8.85 (s, 1 H), 9.54 (s, 1
H, NH), 9.96 (s, 1 H, NH).
13C NMR (50 MHz, DMSO-d6): δ = 113.0, 117.4, 117.8, 120.9,
121.1, 121.4, 122.0, 122.3, 122.4, 123.7, 125.4, 129.7, 129.9, 130.5,
HRMS (ESI): m/z [M + H]+ calcd for C32H20F4N4: 537.1697; found:
537.1698.
Synthesis 2014, 46, 1613–1620
© Georg Thieme Verlag Stuttgart · New York