Preparations of 2-(Substituted amino)pyridines
J . Org. Chem., Vol. 62, No. 18, 1997 6213
Ta ble 3. P r ep a r a tion of 3,4,6-Su bstitu ted P yr id -2-on es 15
elemental analysis found (required)
pyridone 15
R
R1
R2 yield, % mp, °C (solvt) molecular formula
C
H
N
a
C6H5
C6H5
H
92
216-217
C17H13NO
a
(
205-206)
(EtOAc)
b
c
d
e
f
4-MeC6H4
C6H5
H
85
54
57
53
75
31
53
238-239
MeOH)
258-260
EtOAc)
281-282
acetone)
237-238
acetone)
308-309
acetone)
218-220
EtOAc)
248-249
CHCl3)
C18H15NO
82.44
(82.73)
78.04
5.67
(5.79)
5.96
5.31
(5.36)
4.61
(
4-MeOC6H4 4-MeC6H4
H
C19H17NO2
C17H12N2O3
C17H12ClNO
C17H11Cl2NO
C21H14N2O3
C18H15NO
(
(78.33)
(5.88)
(4.81)
b
C6H5
4-O2NC6H4
4-ClC6H4
4-ClC6H4
3-O2NC6H4
C6H5
H
9.56
(
(69.86)
72.35
(72.47)
64.66
(4.14)
4.23
(4.29)
3.50
(9.58)
4.96
(4.97)
4.38
(4.43)
c
(7.86)
5.35
C6H5
H
(
4-ClC6H4
1-naphthyl
C6H5
H
(
(64.58)
(3.51)
g
h
H
(
(73.68)
82.48
(82.73)
(4.12)
5.94
(5.79)
Me
(
(8.18)
a
Lit.16 mp. MS: found 292.0838 [M ], calcd 292.0848 [M ]. MS: found 343.1076 [M + 1], calcd 343.1083 [M + 1].
b
+
+
c
3
7
H), 5.67 (q, J )7.1 Hz, 1H), 7.36-7.48 (m, 2H), 7.53 (t, J )
.1 Hz, 1H), 7.75-7.85 (m, 2H), 8.04 (d, J ) 8.3 Hz, 1H); 13
2-(P iper idin -1-yl)-4-ph en yl-6-(4-tolyl)pyr idin e (14g): 1
H
C
NMR δ 1.67 (m, 6H), 2.38 (s, 3H), 3.67-3.68 (m, 4H), 6.75 (s,
1H), 7.20-7.25 (m, 3H), 7.38-7.47 (m, 3H), 7.63 (d, J ) 6.7
Hz, 2H), 7.97 (d, J ) 8.2 Hz, 2H); 13C NMR δ 21.2, 24.9, 25.6,
46.4, 103.4, 107.8, 126.8, 127.1, 128.3, 128.8, 129.1, 137.5,
138.3, 140.4, 150.8, 155.7, 159.9.
NMR δ 16.8, 57.4, 111.2, 119.1, 123.9, 127.1, 132.7, 145.5,
70.3.
Gen er a l P r oced u r e for th e P r ep a r a tion of 2-(Disu b-
stitu ted a m in o)p yr id in es 14a -k . To a stirred solution of
-(cyanomethyl)benzotriazole (7a ) (0.395 g, 2.5 mmol) and the
1
1
2-(Mor p h olin -1-yl)-4-p h en yl-6-(4-tolyl)p yr id in e (14h ):
1
corresponding 1-substituted 3-phenylprop-2-en-1-one 8 (2.5
mmol) in ethanol (8 mL) was added a corresponding sec-amine
H NMR δ 2.42 (s, 3H), 3.69-3.70 (m, 4H), 3.90-3.91 (m, 4H),
6.75 (s, 1H), 7.29 (d, J ) 6.8 Hz, 2H), 7.36 (s, 1H), 7.47-7.50
1
3
(
2 mL), and the resulting solution was stirred under reflux
for 48 h. The solvent was removed under reduced pressure,
and the residue was dissolved in CH Cl (10 mL), washed with
0% NaOH (2 × 5 mL) and brine, and dried over anhyd
Na SO , and the solvent was removed in vacuo. Column
(m, 3H), 7.66 (d, J ) 6.9 Hz, 2H), 7.99 (d, J ) 7.0 Hz, 2H); C
NMR δ 21.3, 45.8, 66.9, 103.2, 109.1, 126.8,127.1, 128.6, 128.8,
2
2
129.2, 137.0, 138.6, 140.0, 151.1, 155.8, 159.7.
1
-(Dieth yla m in o)-4-p h en yl-6-m eth ylp yr id in e (14i): 1
2
H
2
4
NMR δ 1.19 (t, J ) 7.1 Hz, 6H), 2.43 (s, 3H), 3.56 (q, J ) 7.1
chromatography of the crude product (silica gel, eluent hexane:
ethyl acetate 5:1) gave the corresponding pyridine 14a -k . The
properties of the prepared pyridines are shown in Table 2.
Hz, 4H), 6.43 (s, 1H), 6.58 (s, 1H), 7.32-7.43 (m, 3H), 7.56-
13
7
1
.58 (m, 2H); C NMR δ 13.0, 24.8, 42.3, 100.3, 109.1, 127.0,
28.1, 128.6, 140.5, 150.0, 157.2, 157.8.
1
2
-(Dieth yla m in o)-4,6-d ip h en ylp yr id in e (14a ): H NMR
-(P ip er id in -1-yl)-4-p h en yl-6-m eth ylp yr id in e (14j): 1
2
H
δ 1.26 (t, J ) 7.1 Hz, 6H), 3.65 (q, J ) 7.1 Hz, 4H), 6.58 (s,
NMR δ 1.64-1.67 (m, 6H), 2.45 (s, 3H), 3.56-3.57 (m, 4H),
1
8
1
1
H), 7.20 (s, 1H), 7.34-7.49 (m, 6H), 7.64 (d, J ) 6.7 Hz, 2H),
.10 (d, J ) 7.0 Hz, 2H); 13C NMR δ 13.2, 42.7, 102.2, 106.7,
26.8, 127.1, 128.3, 128.4, 128.8, 140.4, 140.6, 150.6, 155.7,
57.8.
6
2
1
.62 (s, 1H), 6.66 (s, 1H), 7.34-7.45 (m, 3H), 7.55-7.59 (m,
13
H); C NMR δ 24.7, 24.8, 25.6, 46.5, 102.0, 110.7, 127.0,
28.2, 128.7, 140.2, 150.3, 157.1, 160.1.
-(Mor ph olin -1-yl)-4-ph en yl-6-m eth ylpyr idin e (14k): 1
2
H
2
-(P yr r olidin -1-yl)-4,6-diph en ylpyr idin e (14b): 1H NMR
δ 1.99-2.03 (m, 4H), 3.57-3.62 (m, 4H), 6.47 (d, J ) 1.1 Hz,
NMR δ 2.47 (s, 3H), 3.56 (t, J ) 4.9 Hz, 4H), 3.85 (t, J ) 4.8
Hz, 4H), 6.61 (s, 1H), 6.77 (s, 1H), 7.35-7.49 (m, 3H), 7.58 (d,
1
6
1
1
H), 7.23 (d, J ) 1.1 Hz, 1H), 7.33-7.48 (m, 6H), 7.66 (d, J )
.6 Hz, 2H), 8.10 (d, J ) 7.3 Hz, 2H); 13C NMR δ 25.6, 47.8,
03.0, 106.9, 126.9, 127.1, 128.3, 128.4, 128.8, 140.3, 150.3,
55.9, 157.7.
13
J ) 9.0 Hz, 2H); C NMR δ 24.7, 46.0, 66.9, 101.9, 112.2,
1
27.1, 128.5, 128.8, 139.9, 150.7, 157.3, 160.0.
Rea ction of 2-(Ben zotr ia zol-1-yl)a ceton itr ile (7a ) w ith
,3-Dip h en ylp r op -2-en -1-on e (8a ) in t h e P r esen ce of
Na OH. Compounds 7a (0.26 g, 1.8 mmol) and 8a (0.37 g, 1.8
mmol) were added at rt to a stirred solution of NaOH (0.36 g,
.0 mmol) in ethanol (5 mL). After 18 h, the reaction mixture
1
2
-(P ip er id in -1-yl)-4,6-d ip h en ylp yr id in e (14c): 1H NMR
δ 1.62-1.80 (m, 6H), 3.67-3.69 (m, 4H), 6.77 (d, J ) 1.0 Hz,
1
6
4
1
H), 7.26 (d, J ) 1.0 Hz, 1H), 7.34-7.48 (m, 6H), 7.64 (d, J )
.6 Hz, 2H), 8.07 (d, J ) 7.0 Hz, 2H); 13C NMR δ 24.9, 25.6,
6.4, 103.7, 108.1, 126.9, 127.1, 128.4, 128.5, 128.8, 140.2,
40.3, 150.9, 155.7, 159.9.
9
was diluted with water (20 mL), and the formed precipitate A
was filtered, washed with water, and air dried. To the filtrate
was added a solution of HCl (4 N, 20 mL), the resulting
mixture was stirred for 2 h, and the precipitate B was filtered,
washed with water, and air dried. Both crude products were
subjected to column chromatography: product A on silica gel
using hexanes:CH Cl 1:1 as eluting system afforded 0.073 g
2
-(Mor ph olin -1-yl)-4,6-diph en ylpyr idin e (14d): 1H NMR
δ 3.63-3.67 (m, 4H), 3.84-3.87 (m, 4H), 6.74 (s, 1H), 7.35 (s,
1
7
1
H), 7.37-7.48 (m, 6H), 7.63 (d, J ) 6.6 Hz, 2H), 8.06 (d, J )
13
.0 Hz, 2H); C NMR δ 45.7, 66.8, 103.5, 109.4, 126.8, 127.1,
2
2
28.4, 128.6, 128.7, 128.8, 139.8, 139.9, 151.1, 155.8, 159.7.
(15%) of the 2-ethoxy-4,6-diphenylpyridine (13a ); product B
on silica gel using MeOH:CHCl 1:20 as eluting system
2
-(Dieth ylam in o)-4-ph en yl-6-(4-tolyl)pyr idin e (14e): 1
H
3
NMR δ 1.58 (t, J ) 7.1 Hz, 6H), 2.71 (s, 3H), 4.00 (q, J ) 7.1
afforded 0.210 g (47%) of the 4,6-diphenylpyrid-2-one (15a ),
mp 216-218 °C (ethyl acetate). Spectral characteristics and
mp of 15a are consistent with those determined for another
sample of this product obtained by the procedure described
below.
Hz, 4H), 6.88 (s, 1H), 7.50 (s, 1H), 7.56 (d, J ) 8.3 Hz, 2H),
7
.71-7.81 (m, 3H), 7.96 (d, J ) 7.1 Hz, 2H), 8.26 (d, J ) 8.0
13
Hz, 2H); C NMR δ 13.2, 21.2, 42.7, 101.9, 106.3, 126.7, 127.1,
1
28.2, 128.7, 129.1, 137.7, 138.2, 140.7, 150.6, 155.7, 157.7.
-(P yr r olid in -1-yl)-4-p h en yl-6-(4-tolyl)p yr id in e (14f):
H NMR δ 1.99-2.04 (m, 4H), 2.39 (s, 3H), 3.57-3.62 (m, 4H),
.46 (s, 1H), 7.20 (s, 1H), 7.24 (d, J ) 8.0 Hz, 2H), 7.36-7.48
m, 3H), 7.66 (d, J ) 6.8 Hz, 2H), 8.00 (d, J ) 8.0 Hz, 2H); 13
NMR δ 21.3, 25.6, 46.8, 102.7, 106.6, 126.8, 127.1, 128.3, 128.7,
29.1, 137.6, 138.2, 140.4, 150.3, 155.9, 157.7.
2
2-Eth oxy-4,6-d ip h en ylp yr id in e (13a ): prisms; mp 56-
1
1
57 °C; H NMR δ 1.45 (t, J ) 7.1 Hz, 3H), 4.53 (q, J ) 7.1 Hz,
6
2H), 6.86 (d, J ) 1.2 Hz, 1H), 7.37-7.48 (m, 6H), 7.53 (d, J )
1.2 Hz, 1H), 7.63 (d, J ) 6.6 Hz, 2H), 8.07 (d, J ) 6.9 Hz, 2H);
(
C
1
3
C NMR δ 14.8, 61.7, 107.1, 111.6, 126.8, 127.0, 128.6, 128.8,
1
128.9, 138.8, 139.3, 151.9, 155.1, 164.2. Anal. Calcd for