Novel Amination and Deamination
J . Org. Chem., Vol. 64, No. 21, 1999 7971
rido[4,3,2-de]quinoline (4). Yield 88%, mp 265-7 °C, HRMS:
4.06 (m, 2 H), 4.10 (s, 3 H), 3.97 (s, 3 H), 1.84 (m, 2 H), 1.26 (t,
3 H, J ) 7.2 Hz), 1.12 (t, 3 H, J ) 7.2 Hz).
1
4
15
+
calcd for C17
16 2 1 6
H N N O Cl 394.0698, found 394.0698 (M ,
1
15
15
1
)
9
3
C
00%); H NMR (CDCl
3
): δ 9.88 (d, 1 H, N-Ha, J N-Ha
The syntheses of compound 9-12 were carried out by the
similar manner of compound 7 and 8. These compounds were
isolated from the reaction solution as soon as possible and
1
5
15
92.5 Hz), 6.89 (s, 1 H), 6.34 (d, 1 H, N-Hb, J N-Hb )
2.5 Hz), 5.10 (s, 2 H), 4.26 (q, 2 H, J ) 7.2 Hz), 4.13 (s, 3 H),
1
.99 (s, 3 H), 1.28 (t, 3 H, J ) 7.2 Hz). Anal. Calcd for
identified by H NMR spectra and electrospray mass spectra.
1
4
15
17
H
16
N
2
N
1
O
6
Cl: C, 51.72; H, 4.09; N, 10.89; Cl, 8.99.
They are not stable in the solution especially in the basic
solution.
1H-2,3-Dik eto-4-a m in o-5-ch lor o-7,8-d im eth oxyp yr id o-
Found C, 51.48; H, 3.86; N, 10.96; Cl, 9.35.
H -2,3-D i k e t o -4-(1 5 N -p r o p y l)a m i n o -5-c h lo r o -7,8-
1
[
1
4,3,2-d e]qu in olin e (13). A solution of 29 mg (0.10 mmol) of
H-2,3-diketopyrido[4,3,2-de]quinoline (1) in 20 mL of THF
d im eth oxyp yr id o[4,3,2-d e]qu in olin e (5). A solution of 29
mg (0.10 mmol) of 1H-2,3-diketopyrido[4,3,2-de]quinoline (1)
1
5
was mixed with 50 mg of n-propylamine and 5 drops of
triethylamine. The mixture was stirred at room temperature
for 24 h. The resulting solution was then subjected to column
chromatography (5:1 of ethyl acetate to methanol) to give 26
mg of the red product, 1H-2,3-diketo-4-amino-5-chloro-7,8-
dimethoxypyrido[4,3,2-de]quinoline (13). Yield 85%, mp > 300
in 20 mL of THF was mixed with 100 mg of N labeled
1
5
+
-
3 2 2 3
n-propylamine hydrochloride (CH CH CH N H Cl ) and 10
drops of triethylamine. The mixture was stirred at room
temperature for 3 h. The purple intermediate formed during
the reaction was isolated immediately by flash chromatogra-
phy (4:1 of ethyl acetate to hexane and then ethyl acetate) to
1
5
°C. HRMS: calcd for C13
H
10
N
3
O
4
Cl 307.0360, found 307.0361
): δ 11.92 (s, 1 H), 9.57 (s, 1
H), 8.28 (s, 1 H), 7.20 (s, 1 H), 3.90 (s, 3 H), 3.88 (s, 3 H). Anal.
Calcd for C13 Cl: C, 50.75; H, 3.28; N, 13.66; Cl, 11.52.
give 20 mg of the purple 1H-2,3-diketo-4-( N-propyl)amino-
+
1
(M , 100%); H NMR (DMSO-d
6
5
-chloro-7,8-dimethoxypyrido[4,3,2-de]quinoline (5). Yield 57%.
1
4
15
+
ESMS: calcd for C16
H
16
N
2
N
1
O
4
Cl 350.1, found 351.1 (MH ,
1
10 3 4
H N O
1
00%); H NMR (DMSO-d
N-Ha, J N-Ha ) 92 Hz), 7.23 (s, 1 H), 3.90 (s, 3 H), 3.88
6
): δ 11.95 (s, 1 H), 10.85 (d, 1 H,
1
5
15
Found C, 51.03; H, 3.43; N, 13.78; Cl, 11.83.
1-(Eth oxycar bon ylm eth yl)-2,3-diketo-4-am in o-5-ch lor o-
1
5
(
)
s, 3 H), 3.84 (m, 2 H, NCH
7.2 Hz).
-(E t h oxyca r b on ylm et h yl)-2,3-d ik et o-4-(15N-p r op yl)-
2
), 1.72 (m, 2 H), 1.02 (t, 3 H, J
7
,8-d im eth oxyp yr id o[4,3,2-d e]qu in olin e (14). A solution of
3
8 mg (0.10 mmol) of 1-(ethoxycarbonylmethyl)-2,3-diketopy-
1
rido[4,3,2-de]quinoline (2) in 20 mL of THF was mixed with
0 mg of n-propylamine and 5 drops of triethylamine. The
a m in o-5-ch lor o-7,8-d im e t h oxyp yr id o[4,3,2-d e]q u in o-
lin e (6). A solution of 38 mg (0.10 mmol) of 1-(ethoxycarbon-
ylmethyl)-2,3-diketopyrido[4,3,2-de]quinoline (2) in 20 mL of
5
mixture was stirred at room temperature for 24 h. The
resulting solution was then subjected to column chromatog-
raphy (1:1 of ethyl acetate to hexane and then 4:1 of ethyl
acetate to hexane) to give 36 mg of the red product, 1-(ethoxy-
carbonylmethyl)-2,3-diketo-4-amino-5-chloro-7,8-dimethoxypy-
1
5
THF was mixed with 100 mg of N labeled n-propylamine
1
5
+
-
hydrochloride (CH
ethylamine. The mixture was stirred at room temperature for
.5 h. The purple intermediate formed during the reaction was
3 2 2 3
CH CH N H Cl ) and 10 drops of tri-
0
rido[4,3,2-de]quinoline (14). Yield 91%, mp 266-7 °C. HRMS:
isolated immediately by flash chromatography (1:1 of ethyl
acetate to hexane and then 4:1 of ethyl acetate to hexane) to
give 32 mg of the purple 1-(ethoxycarbonylmethyl)-2,3-diketo-
+
calcd for C17
H
16
N
3
3
O
6
Cl 393.0727, found 393.0726 (M , 100%);
1
H NMR (CDCl
.10 (s, 2 H), 4.27 (q, 2 H, J ) 7.2 Hz), 4.13 (s, 3 H), 3.99 (s, 3
Cl:
): δ 9.83 (s, 1 H), 6.90 (s, 1 H), 6.33 (s, 1 H),
5
1
5
4
-( N-propyl)amino-5-chloro-7,8-dimethoxypyrido[4,3,2-de]-
H), 1.28 (t, 3 H, J ) 7.2 Hz). Anal. Calcd for C17
16 3 6
H N O
1
4
15
quinoline (6). Yield 73%. ESMS: calcd for C20
H
22
N
2
N
1
O
6
Cl
): δ 11.62
d, 1 H, N-H, J N-H ) 92 Hz), 6.84 (s, 1 H), 5.10 (s, 2 H),
C, 51.85; H, 4.06; N, 10.67; Cl, 9.02. Found C, 52.18; H, 4.34;
N, 10.78; Cl, 9.20.
+
1
4
(
36.1, found 437.1 (MH , 100%); H NMR (CDCl
3
1
5
15
1
-(Eth oxycar bon ylm eth yl)-2,3-diketo-4-(N-ph en yl)am i-
1
5
4
3
3
4
6
1
1
.23 (q, 2 H, J ) 7.2 Hz), 4.08 (m, 2 H, NCH
2
), 4.13 (s, 3 H),
n o-5-ch lor o-7,8-d im eth oxyp yr id o[4,3,2-d e]qu in olin e (15)-
.97 (s, 3 H), 1.85 (m, 2 H), 1.27 (t, 3 H, J ) 7.2 Hz), 1.12 (t,
.
A solution of 175 mg (0.60 mol) of 1-(ethoxycarbonylmethyl)-
1
3
H, J ) 7.2 Hz). C NMR (CDCl ): δ 12.012, 14.894, 24.756,
15 13
3
2
,3-diketopyrido[4,3,2-de]quinoline (2) in 50 mL of chloroform
1
5
2 2 3
5.661, 49.696 ( NCH CH CH , J N, C ) 8.5 Hz), 58.490,
was placed in a three-neck reaction flask which was connected
with a volumeter system. The reaction system was filled with
air and sealed with water in a U-type tube. Under atmospheric
pressure (745 mmHg) at 23 °C, the solution was injected with
2.793, 63.579, 104.534, 109.045, 111.629, 126.585, 132.946,
41.167, 142.376, 146.149 (4-C, J 15N, C ) 15.8 Hz), 149.966,
58.071, 168.151, 175.159.
13
1
H-2,3-Diketo-4-(N-pr opyl)am in o-5-ch lor o-7,8-dim eth ox-
0
.5 mL of triethylamine followed by 0.5 mL of aniline. The
yp yr id o[4,3,2-d e]qu in olin e (7). A solution of 29 mg (0.10
mmol) of 1H-2,3-diketopyrido[4,3,2-de]quinoline (1) in 20 mL
of THF was mixed with 50 mg of n-propylamine and 5 drops
of triethylamine. The mixture was stirred at room temperature
for 3 h. The purple intermediate formed during the reaction
was isolated immediately by flash chromatography (4:1 of ethyl
acetate to hexane and then ethyl acetate) to give 22 mg of the
purple 1H-2,3-diketo-4-(N-propyl)amino-5-chloro-7,8-dimethox-
ypyrido[4,3,2-de]quinoline (7). Yield 63%. ESMS: calcd for
resulting mixture was stirred at 23 °C under atmospheric
pressure for 24 h, and the difference of the volume in the
reaction atmosphere was measured as 7.4 mL which is
2
equivalent to 0.299 mol of oxygen (O ). The reaction solution
was washed with 1 N of hydrochloric acid (50 mL × 2) and
then subjected to column chromatography (1:1 of ethyl acetate
to hexane and then 4:1 of ethyl acetate to hexane) to give 160
mg of the purple product, 1-(ethoxycarbonylmethyl)-2,3-diketo-
4
-(N-phenyl)amino-5-chloro-7,8-dimethoxypyrido[4,3,2-de]quin-
+
1
C
16
H
16
N
3
O
6
4
Cl 349.1, found 350.1 (MH , 100%); H NMR
): δ 11.95 (s, 1 H), 10.85 (s, 1 H), 7.23 (s, 1 H), 3.90
s, 3 H), 3.88 (s, 3 H), 3.84 (m, 2 H), 1.72 (m, 2 H), 1.02 (t, 3 H,
oline (15). Yield 57%, mp 205-7 °C. HRMS: calcd for
(DMSO-d
+
1
C
23
H
20
N
3
O
6
Cl 469.1041, found 469.1041 (M , 100%); H NMR
(
(
CDCl ): δ 12.15 (s, 1 H), 7.41 (t, 2 H, J ) 7.4 Hz), 7.30 (t, 1
3
J ) 7.2 Hz).
H, J ) 7.4 Hz), 7.18 (d, 2 H, J ) 7.4 Hz), 6.92 (s, 1 H), 5.15 (s,
1
-(Eth oxyca r bon ylm eth yl)-2,3-d ik eto-4-(N-p r op yl)a m i-
2 H), 4.32 (q, 2 H, J ) 7.2 Hz), 4.16 (s, 3 H), 4.02 (s, 3 H), 1.34
n o-5-ch lor o-7,8-d im eth oxyp yr id o[4,3,2-d e]qu in olin e (8)-
20 3 6
(t, 3 H, J ) 7.2 Hz). Anal. Calcd for C23H N O Cl: C, 58.79;
.
A solution of 38 mg (0.10 mmol) of 1-(ethoxycarbonylmethyl)-
H, 4.29; N, 8.94; Cl, 7.55. Found C, 58.68; H, 4.41; N, 9.21; Cl,
7.88.
2
,3-diketopyrido[4,3,2-de]quinoline (2) in 20 mL of THF was
mixed with 50 mg of n-propylamine and 5 drops of triethy-
lamine. The mixture was stirred at room temperature for 0.5
h. The purple intermediate formed during the reaction was
isolated immediately by flash chromatography (1:1 of ethyl
acetate to hexane and then 4:1 of ethyl acetate to hexane) to
give 35 mg of the purple compound, 1-(ethoxycarbonylmethyl)-
1-(E t h o x y c a r b o n y lm e t h y l)-2,3-d i k e t o -4-[N -(3,4-
d im eth oxy)p h en yl]a m in o-5-ch lor o-7,8-d im eth oxyp yr id o-
[4,3,2-d e]qu in olin e (16). A solution of 38 mg (0.10 mmol) of
1-(ethoxycarbonylmethyl)-2,3-diketopyrido[4,3,2-de]quino-
line (2) in 20 mL of chloroform was mixed with 100 mg of 3,4-
dimethoxyaniline and 10 drops of triethylamine. The mixture
was stirred at room temperature for 24 h. The resulting
solution was washed with 1 N of hydrochloric acid (50 mL ×
2) and then subjected to column chromatography (1:1 of ethyl
acetate to hexane and then 4:1 of ethyl acetate to hexane) to
2
,3-diketo-4-(N-propyl)amino-5-chloro-7,8-dimethoxypyrido-
[
4,3,2-de]quinoline (8). Yield 80%. ESMS: calcd for C20H N O -
22 3 6
+
1
Cl 435.1, found 436.1 (MH , 100%); H NMR (CDCl
(
3
): δ 11.58
s, 1 H), 6.82 (s, 1 H), 5.08 (s, 2 H), 4.234 (q, 2 H, J ) 7.2 Hz),