Chemistry of Heterocyclic Compounds 2015, 51(7), 658–663
2
-{6-[(1,2-Oxazinan-2-yl)sulfonyl]hexyl}-1H-pyrrolo-
3,4-c]pyridine-1,3(2H)-dione (1a) and N,N'-bis{6-[(1,2-
oxazinan-2-yl)sulfonyl]hexyl}pyridine-3,4-dicarboxamide
7a) were prepared from compound 6 (200 mg, 1.0 mmol)
and 6-[(1,2-oxazinan-2-yl)sulfonyl]hexan-1-amine (5a)
250 mg, 1.0 mmol).
Compound 1a. Yield 289 mg (76%). H NMR spectrum,
δ, ppm (J, Hz): 1.33–1.43 (2H, m, CH ); 1.50 (2H, quin,
J = 7.6, CH ); 1.60–1.75 (4H, m, 2CH ); 1.81–1.92 (4H, m,
); 3.11–3.17 (2H, m, SO CH ); 3.39 (2H, t, J = 5.4,
); 3.71 (2H, t, J = 7.2, NCH ); 4.11 (2H, t, J = 5.3,
); 7.75 (1H, dd, J = 4.8, J = 1.0, H-7), 9.06 (1H, d,
Compound 1c. Yield 100 mg (77%). The analytical
data were identical with those of compound 1c obtained by
the reaction of pyridine-3,4-dicarboxylic acid (4) and
n-octylamine (5c).
[
(
1
Compound 7c. Yield 18 mg (9%). H NMR spectrum,
(
δ, ppm (J, Hz): 0.82–0.95 (6H, m, 2CH ); 1.24–1.41
3
1
(20H, m, 2NCH
2
CH
3
2
(CH
2
)
5
CH ); 1.53–1.63 (4H, m,
3
2
2NCH CH (CH CH
2
2
2
)
5
); 3.34–3.42 (4H, m, 2NCH ); 7.05
2
2
2
(1H, t, J = 5.7, NH); 7.41 (1H, t, J = 5.4, NH); 7.45 (1H, d,
J = 5.0, H-5 Py), 8.64 (1H, d, J = 5.0, H-6 Py); 8.73 (1H, s,
2
CH
NCH
OCH
2
2
2
13
2
2
2
H-2 Py). C NMR spectrum, δ, ppm: 14.1; 22.6; 26.9; 29.2
(2C); 29.3 (2C); 31.8; 40.4 (2C); 122.3; 129.0; 141.4;
13
+
J = 4.8, H-6), 9.14 (1H, s, H-4). C NMR spectrum, δ, ppm:
149.3; 151.5; 166.6; 167.0. Found, m/z: 390.3124 [M+H] .
2
2.5; 22.8; 24.1; 26.2; 27.9; 28.1; 38.1; 46.4; 47.4; 72.3; 116.7;
C
23
H
40
N
3
O . Calculated, m/z: 390.3115.
2
1
[
25.9; 139.4; 144.7; 155.6; 166.8; 167.2. Found, m/z: 382.1441
2-Octyl-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one
+
M+H] . C17
Compound 7a. Yield 15 mg (2%). H NMR spectrum,
δ, ppm (J, Hz): 1.36–1.78 (16H, m, 8CH ); 1.79–1.96 (8H,
m, 4CH ); 3.07–3.25 (4H, m, 2SO CH ); 3.31–3.48 (8H,
m, 4NCH ); 4.11 (4H, t, J = 5.3, 2OCH ); 6.85–7.00 (1H,
m, NH); 7.24–7.39 (1H, m, NH); 7.51 (1H, d, J = 5.1, H-5 Py);
H
24
N
3
O
5
S. Calculated, m/z: 382.1431.
(2c). Zinc powder (261 mg, 4.0 mmol) was added to a
solution of compound 1c (260 mg, 1.0 mmol) in glacial
AcOH (6.0 ml), and the mixture was refluxed for 4 h, then
cooled to room temperature, and evaporated. The residue
1
2
2
2
2
2
2
was dissolved in CH
NaHCO solution, water, and brine. The extract was dried
over Na SO , concentrated in vacuo, and the residue was
2
Cl (100 ml), washed with saturated
2
3
8
.72 (1H, dd, J = 5.1, J = 0.9, H-6 Py); 8.81 (1H, s, H-2 Py).
Found, m/z: 632.2797 [M+H] . C27
m/z: 632.2783.
2
4
+
H
46
N
5
O
8
S
2
. Calculated,
purified by flash chromatography (eluent EtOH in CHCl ,
3
0–5%) to provide 110 mg (45%) of the product as a light-
1
6
-(1,3-Dioxo-1H-pyrrolo[3,4-c]pyridin-2(3H)-yl)-N-iso-
yellow oil. H NMR spectrum, δ, ppm (J, Hz): 0.87 (3H, t,
propyl-N-[2-(morpholin-4-yl)ethoxy]hexane-1-sulfon-
amide (1b) and N,N'-bis(6-{N-isopropyl-N-[2-(morpholin-
J = 6.7, CH
m, NCH CH
CH ); 7.42 (1H, d, J = 5.0, H-7); 8.74 (1H, d, J = 5.0, H-6);
+
3
); 1.17–1.40 (10H, m, (CH
2
2
)
5
); 1.55–1.75 (2H,
2
2
); 3.61 (2H, t, J = 7.3, NCH
); 4.42 (2H, s,
4
(
-yl)ethoxy]sulfamoyl}hexyl)pyridine-3,4-dicarboxamide
2
7b) were prepared from compound 6 (200 mg, 2.0 mmol)
and 6-amino-N-isopropyl-N-[2-(morpholin-4-yl)ethoxy]hexane-
-sulfonamide (5b) (352 mg, 2.0 mmol).
9.08 (1H, s, H-4). Mass spectrum, m/z: 247 [M+H]
Preparation of 1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-
3-ones 2a–c, 8a–c (General method). A mixture of a
1,3-dioxopyrrolo[3,4-c]pyridine derivative 1a–c (1 equiv)
and Sn powder (3 equiv) in concentrated HCl and glacial
AcOH (1:1, 3 ml/mmol of compound 1a–c) was stirred for
24 h at room temperature. The reaction mixture was filtered,
evaporated, and the residue was dissolved in EtOAc. The
1
1
Compound 1b. Yield 360 mg (74%). H NMR spectrum,
δ, ppm (J, Hz): 1.26 (6H, d, J = 6.6, CH(CH ); 1.39 (2H,
); 1.51 (2H, quin, J = 7.6, CH ); 1.70
2H, quin, J = 7.4, CH ); 1.89 (2H, quin, J = 7.8, CH
.46–2.51 (4H, m, N(CH ); 2.60 (2H, t, J = 5.7, NCH
.08 (2H, br. s, SO CH ); 3.66–3.71 (4H, m, O(CH
.71 (2H, t, J = 7.4, NCH
.14 (2H, br. s, OCH ); 7.74 (1H, dd, J = 4.8, J = 1.0, H-7);
)
3 2
quin, J = 7.5, CH
2
2
(
2
2
2
2
);
);
);
2
3
3
4
9
2 2
)
2
2
2
)
obtained solution was washed with saturated NaHCO
concentrated in vacuo, and the residue was purified by flash
chromatography (eluent EtOH in CHCl , gradient 0–15%) to
3
, water,
2
); 3.99 (1H, sept, J = 6.6, CH);
2
3
.06 (1H, d, J = 4.8, H-6); 9.14 (1H, d, J = 1.0, H-4).
C NMR spectrum, δ, ppm: 22.7; 26.3; 28.1; 28.2; 38.1;
8.9; 53.4; 53.9; 56.8; 67.0; 76.1; 77.0; 116.8; 125.9;
provide the products 2a–c and 8a–c as light-yellow oils.
2-{6-[(1,2-Oxazinan-2-yl)sulfonyl]hexyl}-1,2-dihydro-
3H-pyrrolo[3,4-c]pyridin-3-one (2a) and 2-{6-[(1,2-
oxazinan-2-yl)sulfonyl]hexyl}-1-hydroxy-1,2-dihydro-3H-
pyrrolo[3,4-c]pyridin-3-one (8a) were prepared from
compound 1a (145 mg, 0.38 mmol).
1
3
4
1
[
39.4; 144.7; 155.6; 166.8; 167.2. Found, m/z: 483.2286
+
M+H] . C22
H
35
N
4
O S. Calculated, m/z: 483.2272.
6
1
Compound 7b. Yield 96 mg (12%). H NMR spectrum,
δ, ppm (J, Hz): 1.26 (12H, d, J = 6.6, 2CH(CH ); 1.38–
1
3
)
2
Compound 2a. Yield 54 mg (37%). H NMR spectrum,
1
.74 (12H, m, 6CH
2
); 1.81–2.01 (4H, m, 2CH
); 2.61 (4H, t, J = 5.7, NCH
); 3.34–3.50 (4H, m, 2NCH
2
); 2.43–2.54
δ, ppm (J, Hz): 1.40 (2H, quin, J = 7.5, CH
2
); 1.52 (2H,
); 1.81–1.92
); 3.38 (2H, t,
); 4.10 (2H, t,
); 7.43 (1H, d, J = 5.1,
(
8H, m, 2N(CH
2
)
2
2
); 3.10 (4H,
); 3.63–3.74
quin, J = 7.5, CH
(4H, m, 2CH ); 3.11–3.17 (2H, m, SO
J = 5.5, ONCH
J = 5.3, OCH
2
); 1.64–1.74 (4H, m, 2CH
2
br. s, 2SO
2
CH
2
2
2
2
CH
2
(
8H, m, 2O(CH
2
)
2
); 3.97 (1H, sept, J = 6.6, CH); 3.97 (1H,
2
); 3.62 (2H, t, J = 7.3, NCH
2
sept, J = 6.6, CH); 4.08–4.20 (4H, m, 2OCH
1H, m, NH); 7.24–7.36 (1H, m, NH); 7.52 (1H, dd,
J = 5.3, J = 0.7, H-5 Py); 8.74 (1H, d, J = 5.3, H-6 Py);
2
); 6.88–6.99
2
); 4.41 (2H, s, CH
2
(
H-7); 8.75 (1H, d, J = 5.1, H-6); 9.08 (1H, s, H-4). Mass
+ +
spectrum, m/z: 390 [M+Na] , 368 [M+H] .
+
1
8
C
.78 (1H, d, J = 0.7, H-2 Py). Found, m/z: 834.4472 [M+H] .
Compound 8a. Yield 32 mg (23%). H NMR spectrum,
37
2
H
68
N
7
O
10
S
2
. Calculated, m/z: 834.4464.
δ, ppm (J, Hz): 1.38 (2H, quin, J = 7.5, CH
2
); 1.50 (2H,
, OH); 1.78–
); 3.06–3.16 (2H, m, SO CH ); 3.35
(2H, t, J = 5.5, ONCH ); 3.44 (1H, ddd, J = 13.9, J = 8.1,
J = 6.0) and 3.61 (1H, dt, J = 13.9, J = 7.3, NCH ); 4.09
-Octyl-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione (1c)
quin, J = 7.5, CH
2
); 1.60–1.76 (5H, m, 2CH
2
and N,N'-dioctylpyridine-3,4-dicarboxamide (7c) were
prepared from compound 6 (100 mg, 0.50 mmol) and
n-octylamine (5c) (0.083 ml, 0.50 mmol).
1.92 (4H, m, 2CH
2
2
2
2
2
6
61