Full Papers
13
1
H, OH); C NMR ([D ]DMSO): δ=50.7 (br, C-2“), 61.7 (C-8b), 66.2
(m, 1H, H-3”), 4.12 (br s, 2H, 2’-NH ), 5.28 (s, 1H, H-8b), 6.66 (t,
6
2
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
(
1
C-3”),115.6 (C-3’), 115.9 (C-1), 120.0 (C-5’), 121.4 (C-7), 123.0 (C-3),
24.5 (C-1’), 127.4 (C-8a), 128.8 (C-6’), 129.2 (C-3’), 129.4 (C-8), 130.0
(C-4), 143.3 (C-4a), 146.7 (C-6), 154.7 (C-2’), 155.2 (C-2); elemental
analysis calcd (%) for C20 (336.39): C 71.41, H 5.99, N 8.33;
found: C 71.48, H 5.96, N 8.37.
7.5 Hz, 1H, H-5’), 6.71 (d, 7.9 Hz, 1H, H-3’), 7.03 (t, 7.6 Hz, 1H, H-4’),
7.10 (d, 8.9 Hz, 1H, H-3), 7.23 (t, 7.5 Hz, 1H, H-6), 7.33 (d, 7.7 Hz, 1H,
H-6’), 7.36 (ddd, 8.5, 7.0, 1.4 Hz, 1H, H-7), 7.68 (d, 9.0 Hz, 1H, H-4),
7.71 (,d, 8.2 Hz, 1H, H-5), 7.76 (d, 8.6 Hz, 1H, H-8), 13.37 (br s, 1H, 2-
H N O
20 2 3
1
3
OH); C NMR (CD Cl ): δ= 53.9 (br, C-2“), 67.0 (C-3”),114.7 (br, C-1),
2
2
1
1
17.1 (C-3’), 119.7 (br, C-5’), 120.0 (C-3), 121.8 (C-8), 122.9 (C-6),
23.0 (br, C-1’), 126.8 (C-7), 129.0 (C-5), 129.0 (C-4a), 129.3 (C-4’),
7
aR*,15S*-15-(2-Hydroxyphenyl)-Isoquinolino[1’,2’:2,3][1,3]-
129.8 (C-4), 130.6 (br, C-6’), 133.0 (C-8a), 145.0 (C-2’), 155.7 (C-2), C-
Oxazin-o[5,6-f]Quinolin (22a)
8b could not be detected (very broad line); elemental analysis calcd
(%) for C21
H N O (334.17): C 75.42, H 6.63, N 8.38; found: C 75.45,
22 2 2
Aminoquinolinol 19 (40 mg, 0.12 mmol), dihydroisoquinoline 12
H 6.60, N 8.37.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
(23 mg, 0.18 mmol) and 1,4-dioxane (5 mL) were placed in a 10 mL
reaction vial and heated in a CEM microwave reactor under the
conditions given in Table 1. The solvent was removed in vacuo, and
the residue was isolated by crystallisation from MeOH (5 mL) and
recrystallized from iPr O (10 mL). R =0.38 (n-hexane/ EtOAc, 2:1);
Benz[a]acridine (26)
The synthetic protocol applied to achieve 25 was repeated, and the
reaction was driven till the formation of 26 (5 hours). After removal
of the catalyst, the filtrate was concentrated under reduced
pressure and the crude reaction mixture was purified by column
chromatography (n-hexane:EtOAc, 2:1) resulting in 26 (0.32 g,
2
f
1
3
4 mg (90%). Light brown crystals; m.p. 208–209°C; H NMR ([D ]
6
DMSO): δ=2.84 (br d, J=16.0 Hz, 1H, H-12), 3.05 (ddd, J=16.7, 8.6,
8
.6 Hz, 1H, H-12), 3.16 (m, 2H, H-13), 5.78 (s, 2H, H-7a, H-15), 6.61 (t,
J=7.0 Hz, 1H, H-4’), 6.66 (m, 1H, H-5’), 6.93 (d, J=7.7 Hz, 1H, H-2’),
7.09 (t, J=8.0 Hz, 1H, H-3’), 7.24 and 7.33 (2 x m, 2H and 1H, H-9, H-
[24]
(69%); Beige crystals; m.p. 129–130°C (Lit.: mp 130–131°C).
1
2
(
1
8
0, H-11), 7.34 (d, J=9.2 Hz, 1H, H-6), 7.36 (dd, J=8.5, 4.1 Hz, 1H, H-
), 7.41 (br d, J=7.6 Hz, 1H, H-8), 7.63 (br d, J=7.9 Hz, 1H, H-1), 7.89
d, J=9.2 Hz, 1H, H-5), 8.68 (dd, J=4.2-1.6 Hz, 1H, H-3), 9.84 (br s,
General Procedure for the Synthesis of Quinazolines (28b,
30b and 32b)
13
H, H-1’); C NMR ([D ]DMSO): δ= 28.5(C-12), 44.5(C-13), 55.9(C-15),
6
2.0(C-7a), 111.3(C-15a), 115.6(C-2’), 118.4(C-4’), 121.5(C-2 or C-6),
A mixture of diaminonaphtol 25 (67 mg 0.2 mmol) and 3,4-dihydro-
β-carboline 6 (50 mg, 0.3 mmol), or 3,4-dihydroisoquinoline 12
121.9(C-6 or C-2), 125.9(C-9), 126.5(C-15b), 128.5(C-10 or C-11),
128.7(C-3’), 128.8(C-5a’), 128.9(C-8), 128.9(C-11 or C-10), 129.5(C-5’),
1
(
(
39.4 mg, 0.3 mmol) or 6,7-dihydrothieno[3,2-c]pyridine 15
41.2 mg, 0.3 mmol), in 1,4-dioxane (5 mL) was placed in a 10 mL
29.8(C-5), 130.4(C-1), 132.2(C-7b), 134.9 (C-11a), 143.9(C-4a),
47.3(C-3), 151.8(C-6a), 155.1(C-1’); elemental analysis calcd (%) for
1
pressurized reaction vial and heated in a CEM SP microwave reactor
under the conditions given in Table 2. The solvent was removed
under reduced pressure and the residue was isolated by crystal-
lization from MeOH and recrystallized.
C H N O (380.45): C 78.93, H 5.30, N 7.36; found: C 78.89, H 5.36,
N 7.71.
2
5
20
2
2
1
(
-[(2-Nitrophenyl)-Morpholin-4-yl-Methyl]-Naphthalen-2-ol
24)
5S*,13bS*-7-(2-Hydroxynaphth-1-yl)-[2,3-a]-β-Carbolino-
[2,1-b]Quinazoline (28b)
50 ml round-bottom flask was charged with 2-naphthol (0.72 g,
5 mmol), morpholine (0.48 g, 5.5 mmol) and 2-nitrobenzaldehyde
Recrystallized from iPr O (6 mL); R =0.38 (n-hexane/EtOAc 2:1);
2
f
(0.79 g, 5.25 mmol). The mixture was stirred and heated under
1
7
6 mg (91%). Beige crystals; m.p 182–183°C; H NMR ([D ]DMSO):
6
solvent-free conditions at 70°C for 6 hours. The mixture was
δ= 2.71 (m, 1H, H-8), 2.79 (m, 1H, H-8), 2.80 (m, 1H, H-7), 3.09 (m,
1H, H-7), 5.27 (br s, 1H, H-13b), 6.10 (s, 1H, H-5), 6.41 (d, J=8.0 Hz
purified by column chromatography (n-hexane: EtOAc, 2:1); 1.31 g
1
(
(
72%). Yellow crystals; m.p. 148–149°C; H NMR (CD Cl ): δ=2.63
2
2
1
H, H-4), 6.48 (m, 1H, H-14), 6.49 (m, 1H, H-3), 6.80 (d, J =7.5 Hz, 1H,
H-1), 7.01 (m, 2H, H-11, H-3’), 7.02 (m, 1H, H-2’), 7.14 (d, J=8.4 Hz,
H, H-9), 7.38 (t, J=7.4 Hz, 1H, H-6’), 7.45 (m, 2H, H-10, H-12), 7.59
t, J=7.6 Hz, 1H, H-7’), 7.79 (d, J=8.8 Hz, 1H, H-4’), 7.89 (d, J=
.8 Hz, 1H, H-5’), 8.29 (d, J=8.6 Hz, 1H, H-8’), 11.09 (s, 1H, H-13),
dt, 11.8, 3.0 Hz, 1H, H-2“), 3.09 (d, 11.7 Hz, 1H, H-2”), 3.74 (dt, 11.7,
1.7 Hz, 1H, H-3“), 3.85 (t, 12.5 Hz, 1H, H-3”), 6.11 (s, 1H, H-8b), 7.13
1
(
(
d, 8.9 Hz, 1H, H-3), 7.24 (ddd, 8.0, 6.9, 1.1 Hz, 1H, H-6), 7.36 (ddd,
8
1
7
1
.6, 7.1, 1.5 Hz, 1H, H-7), 7.40 (dt, 7.8, 1.4 Hz, 1H, H-4’), 7.49 (dt, 7.7,
.3 Hz, 1H, H-5’), 7.68 (d, 8.6 Hz, 1H, H-8), 7.71 (d, 8.1 Hz, 1H, H-5),
.72 (d, 8.9 Hz, 1H, H-4), 7.85 (dd, 8.2, 1.3 Hz, 1H, H-3’), 7.88 (dd, 8.1,
7
1
3
11.82 (br s, 1H, H-2’); C ([D
]DMSO): δ= 21.0(C-8), 47.7(C-7), 61.0(C-
6
13
5
1
1
7
1
), 68.2(C-13b), 108.2(C-8b), 111.5(C-12), 116.5(C-1), 117.8(C-1’),
.5 Hz, 1H, H-6’), 13.46 (br s, 1H, 2-OH); C NMR (CD Cl ): δ=54.0
2
2
18.2(C-10), 119.0(C-3 or C3’), 119.4(C-3’ or C-3), 119.4(C-11),
21.5(C-9), 121.8(C-8’), 122.6(C-6’), 123.8(C-4a), 125.8(C-8a), 127.1(C-
’ or C-2), 127.2(C-2 or C-7), 127.3(C-4), 128.0(C-4a’), 128.7(C-5’),
29.3(C-4’), 131.5(C-13a), 134.1(C-8a’), 136.3(C-12a), 143.0(C-14a),
(C-2“), 64.1 (C-8b), 66.9 (C-3”), 114.5 (C-1), 120.3 (C-3), 120.8 (C-8),
123.1 (C-6), 124.7 (C-3’), 127.3 (C-7), 129.0 (C-4a), 129.1 (C-5), 129.6
(
C-4’), 130.6 (C-4), 131.5 (C-6’), 132.8 (C-8a), 133.0 (C-1’), 134.1 (C-5’),
50.6 (C-2’), 156.5 (C-2); elemental analysis calcd (%) for C H N O
4
1
2
1
20
2
155.5(C-2’), elemental analysis calcd (%) for C H N O (417.51): C
2
6
22
3
(364.40): C 69.22, H 5.53, N 7.69; found: C 69.30, H 5.50, N 7.72.
80.55, H 5.55, N 10.06; Found: C 80.48, H 5.57, N 10.04.
1-[(2-Aminophenyl)-Morpholin-4-yl-Methyl]-Naphthalen-2-ol
25)
5
S*,12bS*-7-(2-Hydroxynaphth-1-yl)-[2,3-a]Isoquinolino-
(
[
2,1-b]-Quinazoline (30b)
(0.73 g, 2 mmol) of 24 was dissolved in 50 ml of EtOH and 0.2 g of
Recrystallized from iPr O (7 mL); R =0.38 (n-hexane/EtOAc 2:1);
2
f
5% Pd/C catalyst was added. The mixture was hydrogenated at
atmospheric pressure for 1 hour. After filtration of the catalyst, the
solvent was removed and the residue was crystallized from Et O
1
6
2
2
7 mg (89%). White crystals; m.p. 191–192°C; H NMR (CD Cl ): δ=
2
2
.61 (ψt, J=13.8 Hz, 1H, H-7), 2.71 (d, J=14.7 Hz, 1H, H-8), 3.19 (m,
H, H-7, H-8), 4.36 (d, J=5.6 Hz, 1H, H-13), 5.14 (d, J=5.9 Hz, 1H, H-
2
(
30 mL) and recrystallized from iPr O (18 mL); 0.5 g (77%). Beige
2
1
12b), 5.83 (s, 1H, H-5), 6.54 (m, 1H, H-4), 6.57 (m, 1H, H-3), 6.87 (d,
J=7.9 Hz, 1H, H-1), 7.06 (m, 2H, H-2, H-3’), 7.19 (d, J=7.2 Hz, 1H, H-
crystals; m.p. 133–134°C; H NMR (CD Cl ): δ=2.51 (ddd, 12.1, 9.3,
2
2
3
.1 Hz, 1H, H-2“), 2.97 (m, 1H, H-2”), 3.76 (t, 9.2 Hz, 1H, H-3“), 3.82
ChemistryOpen 2019, 8, 961–971
970
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA