8
I.-M. Moise et al. / Bioorg. Med. Chem. xxx (2016) xxx–xxx
6
6
7
.86 (td, J = 7.4, 1.3 Hz, 2H, ArH), 6.89 (dd, J = 8.8, 2.6 Hz, 1H, ArH),
6.1.3.6.
(10).
10-(3-Hydroxy-4-methoxybenzyl)-10H-phenoxazine
The general procedure was followed with 4-methoxy-
.97 (td, J = 7.4, 1.5 Hz, 2H, ArH), 7.07 (dd, J = 7.6, 1.6 Hz, 2H, ArH),
19
.27 (d, J = 2.9 Hz, 1H, ArH), 7.29 (d, J = 8.4 Hz, 1H, ArH). F NMR
3-hydroxybenzyl bromide 16 (0.64 g, 2.9 mmol), phenoxazine 20
(0.59 g, 3.2 mmol) and sodium hydride (0.078 g, 3.2 mmol) in
7 mL of DMF. White powder; mp (EtOAc) = 151–152 °C; 0.23 g
13
(
CDCl
3
, 376 MHz) d (ppm): ꢀ61.2 (s, 3F, CF
3
). C NMR (CDCl
3
,
1
00 MHz) d (ppm): 48.1 (q, J = 3.9 Hz, CH ), 54.5 (CH
2
3
), 111.8 (d,
ꢀ1
J = 6.2 Hz, CH), 114.2 (2CH), 115.7 (CH), 121.6 (2CH), 122.0 (2C),
(0.72 mmol, 23% yield). IR
m (cm ): 3439, 1590, 1486, 1374,
1
1
23.2 (q, J = 271.8 Hz, C), 125.1 (C), 125.8 (2CH), 126.3 (2CH),
27.2 (q, J = 31.6 Hz, C), 128.9 (CH), 143.0 (2C), 157.4 (C). Elemental
1265, 1243, 1195, 1123, 1027, 942, 916, 870, 829, 794, 741, 610,
1
579, 522, 450. H NMR (CDCl
OCH ), 4.67 (s, 2H, CH ), 5.61 (s, 1H, ArOH), 6.33 (d, J = 7.1 Hz,
2H, ArH), 6.61–6.71 (m, 6H, ArH), 6.75–6.80 (m, J = 8.6, 2.0 Hz,
3
, 400 MHz) d (ppm): 3.86 (s, 3H,
Anal. Calcd for C21
H
16
F
3
NOS: C, 65.10; H, 4.16; N, 3.36. Found: C,
3
2
6
5.37; H, 3.94; N, 3.48.
1
3
2
H, ArH), 6.87 (d, J = 2.0 Hz, 1H, ArH). C NMR (CDCl
3
, 100 MHz)
6
.1.3.3. 10-(3-Hydroxy-4-methoxybenzyl)-10H-phenothiazine
The general procedure was followed with 4-methoxy-3-
hydroxybenzyl bromide 16 (0.94 g, 4.3 mmol), phenothiazine 19
0.95 g, 4.8 mmol) and sodium hydride (0.116 g, 4.8 mmol) in
mL of DMF. White powder; mp (EtOAc) = 135–137 °C; 0.38 g
d (ppm): 48.7 (CH ), 56.0 (CH ), 111.0 (2CH), 112.2 (2CH), 112.3
(2CH), 115.2 (CH), 117.4 (CH), 121.1 (CH), 123.6 (2CH), 129.4 (C),
133.8 (C), 145.1 (2C), 145.7 (2C), 146.0 (C). Elemental Anal. Calcd
for C20H17NO : C, 75.22; H, 5.37; N, 4.39. Found: C, 75.37; H,
3
5.45; N, 4.62.
2
3
(
7).
(
7
ꢀ1
(
1.13 mmol, 26% yield). IR
m
(cm ): 3506, 3339, 1593, 1505,
1
7
OCH
2
(
459, 1436, 1361, 1303, 1253, 1215, 1123, 1019, 937, 874, 802,
6.1.3.7.
(11).
10-(3-Fluoro-4-methoxybenzyl)-10H-phenoxazine
The general procedure was followed with 4-methoxy-
1
41, 493, 432. H NMR (CDCl
), 4.98 (s, 2H, CH ), 5.60 (s, 1H, ArOH), 6.65 (d, J = 8.7 Hz,
H, ArH), 6.77 (s, 1H, ArH), 6.85 (td, J = 7.3, 1.4 Hz, 2H, ArH), 6.89
s, 1H, ArH), 6.94–7.05 (m, 3H, ArH) 7.06 (dd, J = 7.3, 1.4 Hz, 2H,
3
, 400 MHz) d (ppm): 3.86 (s, 3H,
3
2
3-fluorobenzyl bromide 15 (0.25 g, 1.1 mmol), phenoxazine 20
(0.23 g, 1.3 mmol) and sodium hydride (0.031 g, 1.3 mmol) in
5 mL of DMF. Grey solid; mp (EtOAc) = 131–132 °C; 0.15 g
(0.47 mmol, 41% yield). IR
1
3
ꢀ1
ArH). C NMR (CDCl
1
1
3
, 100 MHz) d (ppm): 52.2 (CH
10.8 (CH), 112.8 (CH), 115.5 (2CH), 118.1 (CH), 122.4 (2CH),
23.1 (2C), 126.8 (2CH), 127.2 (2CH), 129.7 (C), 144.5 (2C), 145.5
S: C, 71.62; H,
2
), 55.9 (CH
3
),
m
(cm ): 1628, 1592, 1488, 1433,
1380, 1304, 1267, 1222, 1115, 1022, 935, 863, 832, 731, 662,
1
609, 582, 522, 449. H NMR (CDCl
(s, 3H, OCH ), 4.69 (s, 2H, CH ), 6.30 (d, J = 7.6 Hz, 2H, ArH), 6.66–
6.73 (m, 6H, ArH), 6.90 (t, J = 8.4 Hz, 1H, ArH), 7.02 (t, J = 8.8 Hz,
3
, 400 MHz) d (ppm): 3.87
(
C), 145.8 (C). Elemental Anal. Calcd for C20
H17NO
2
3
2
5
.11; N, 4.18. Found: C, 71.39; H, 5.40; N, 4.32.
1
9
2
H, ArH).
J = 10.3 Hz, 1F, ArF). C NMR (CDCl
(CH ), 56.3 (CH ), 112.1 (2CH), 113.9 (d, J = 5.5 Hz, CH), 114.1 (d,
F
NMR (CDCl
3
,
376 MHz)
d
(ppm): ꢀ134.0 (t,
1
3
6
.1.3.4.
10-(3-Fluoro-4-methoxybenzyl)-10H-phenothiazine
3
, 100 MHz) d (ppm): 48.5
(
8).
The general procedure was followed with 4-methoxy-3-
2
3
fluorobenzyl bromide 15 (0.25 g, 1.1 mmol), phenothiazine 19
0.25 g, 1.3 mmol) and sodium hydride (0.031 g, 1.3 mmol) in
mL of DMF. Violet powder; mp (EtOAc) = 148–151 °C; 0.22 g
J = 16.1 Hz, CH), 115.3 (2CH), 121.4 (2CH), 121.5 (d, J = 31.0 Hz,
CH), 123.7 (2CH), 129.3 (d, J = 6.2 Hz, C), 133.6 (2C), 145.1 (2C),
146.4 (d, J = 10.8 Hz, C), 152.8 (d, J = 244.5 Hz, C). Elemental Anal.
(
5
ꢀ1
(
1
7
0.65 mmol, 57% yield). IR
m
(cm ): 3018, 2926, 1567, 1514,
457, 1361, 1291, 1254, 1211, 1121, 1025, 933, 878, 848, 813,
43, 643, 531, 503, 432. 1H NMR (CDCl
, 400 MHz) d (ppm): 3.86
), 5.00 (s, 2H, CH ), 6.64 (dd, J = 8.4, 1.4 Hz, 2H, ArH),
.87 (td, J = 7.6, 1.4 Hz, 2H, ArH), 6.91 (d, J = 8.4 Hz, 1H, ArH),
Calcd for C20
2
H16FNO : C, 74.75; H, 5.02; N, 4.36. Found: C, 74.59;
H, 5.24; N, 4.63.
3
(
s, 3H, OCH
3
2
6.1.3.8.
dibenzo[b,f]azepine (12).
5-(3-Fluoro-4-methoxybenzyl)-10,11-dihydro-5H-
The general procedure was fol-
6
6
1
9
.97–7.08 (m, 4H, ArH), 7.10 (dd, J = 7.8, 1.8 Hz, 2H, ArH).
, 376 MHz) d (ppm): ꢀ134.3 (dd, J = 12.3, 8.4 Hz, 1F,
ArF). C NMR (CDCl , 100 MHz) d (ppm): 51.7 (CH ), 56.3 (CH ),
13.6 (d, J = 2.3 Hz, CH), 114.5 (d, J = 21.7 Hz, CH), 115.4 (2CH),
F
lowed with 4-methoxy-3-fluorobenzyl bromide 15 (0.30 g,
1.4 mmol), 10,11-dihydro-5H-dibenzo[b,f]azepine 21 (0.29 g,
1.5 mmol) and sodium hydride (0.036 g, 1.5 mmol) in 5 mL of
NMR (CDCl
3
1
3
3
2
3
ꢀ1
1
1
1
DMF. Colorless oil; 0.30 g (0.90 mmol, 65% yield). IR m (cm ):
22.3 (d, J = 4.4 Hz, CH), 122.6 (2CH), 123.5 (2C), 126.9 (2CH),
27.2 (2CH), 129.6 (d, J = 5.7 Hz, C), 144.3 (2C), 146.5 (d,
3016, 2913, 2838, 1586, 1515, 1485, 1440, 1369, 1324, 1269,
1215, 1111, 1026, 937, 913, 869, 809, 744, 639, 593. 1H NMR
J = 10.8 Hz, C), 152.6 (d, J = 247.1 Hz, C). Elemental Anal. Calcd for
16FNOS: C, 71.19; H, 4.78; N, 4.15. Found: C, 71.10; H, 5.13;
N, 4.21.
(CDCl
4.86 (s, 2H, CH
ArH), 7.05–7.12 (m, 8H, ArH).
ppm): ꢀ135.4 (sym m, J = 9.4 Hz, 1F, ArF). C NMR (CDCl
100 MHz) d (ppm): 32.4 (2CH ), 54.6 (d, J = 1.5 Hz, CH ), 56.1
(CH ), 113.0 (d, J = 2.3 Hz, CH), 115.6 (d, J = 19.4 Hz, CH), 120.0
(2CH), 122.6 (2CH), 123.6 (d, J = 3.3 Hz, CH), 126.3 (2CH), 129.8
(2CH), 131.6 (d, J = 5.6 Hz, C), 134.0 (2C), 147.9 (2C), 146.3 (d,
J = 12.7 Hz, C), 152.3 (d, J = 245.8 Hz, C). Elemental Anal. Calcd for
3
, 400 MHz) d (ppm): 3.22 (s, 4H, 2CH
2 3
), 3.80 (s, 3H, OCH ),
C
20
H
2
), 6.81 (t, J = 8.4 Hz, 1H, ArH), 6.86–6.90 (m, 2H,
1
9
3
F NMR (CDCl , 376 MHz) d
1
3
(
3
,
6
.1.3.5.
10-[4-Methoxy-2-(trifluoromethyl)benzyl]-10H-phe-
The general procedure was followed with
-methoxy-2-(trifluoromethyl)benzyl bromide 18 (0.5 g,
.9 mmol), phenoxazine 20 (0.38 g, 2.1 mmol) and sodium hydride
2
2
noxazine (9).
4
1
3
(
0.05 g, 2.1 mmol) in 7 mL of DMF. White powder; mp (EtOAc)
ꢀ1
=
1
1
4
143–145 °C; 0.60 g (1.62 mmol, 87% yield). IR
m
(cm ): 1622,
22
C H20FNO: C, 79.26; H, 6.05; N, 4.20. Found: C, 79.51; H, 6.39;
N, 4.52.
578, 1489, 1428, 1380, 1311, 1272, 1229, 1200, 1150, 1118,
1
034, 911, 880, 839, 731, 672, 572, 534, 487, 449. H NMR (CDCl
3
,
00 MHz) d (ppm): 3.81 (s, 3H, OCH ), 4.86 (s, 2H, CH ), 6.22 (dd,
3
2
6.1.3.9.
(13).
10-(3-Fluoro-4-methoxybenzyl)acridin-9(10H)-one
The general procedure was followed with 4-methoxy-
J = 8.3, 2.3 Hz, 2H, ArH), 6.60–6.74 (m, 6H, ArH), 6.93 (d,
J = 7.8 Hz, 1H, ArH), 7.27 (d, J = 2.5 Hz, 1H, ArH), 7.32 (d,
3-fluorobenzyl bromide 15 (0.30 g, 1.4 mmol), acridin-9(10H)-one
22 (0.29 g, 1.5 mmol) and sodium hydride (0.036 g, 1.5 mmol) in
5 mL of DMF. White powder; mp (EtOAc) = 170–172 °C; 0.29 g
1
9
J = 8.5 Hz, 1H, ArH). F NMR (CDCl
3
, 376 MHz) d (ppm): ꢀ61.4 (s,
, 100 MHz) d (ppm): 41.6 (q, J = 3.9 Hz,
), 112.0 (2CH), 113.1 (q, J = 6.1 Hz, CH), 115.3
2CH), 116.8 (CH), 121.4 (2CH), 123.7 (2CH), 124.2 (q,
J = 273.8 Hz, C), 125.6 (C), 128.6 (CH), 128.7 (q, J = 31.1 Hz, C),
33.4 (2C), 145.0 (2C), 158.6 (C). Elemental Anal. Calcd for C21
NO : C, 67.92; H, 4.34; N, 3.77. Found: C, 67.69; H, 4.61; N, 3.83.
1
3
3
F, CF
3 3
). C NMR (CDCl
ꢀ1
CH ), 55.5 (CH
2
3
(0.87 mmol, 64% yield). IR
m (cm ): 1596, 1514, 1488, 1460,
(
1380, 1354, 1280, 1221, 1177, 1121, 1051, 1024, 955, 934, 875,
1
811, 756, 673, 643, 538, 503. H NMR (CDCl
3.84 (s, 3H, OCH ), 5.48 (s, 2H, CH ), 6.80–6.90 (m, 3H, ArH),
7.24–7.32 (m, 4H, ArH), 7.61 (t, J = 8.8 Hz, 2H, ArH), 8.56
3
, 400 MHz) d (ppm):
1
H
16
-
3
2
F
3
2