G. Koza, M. Balci / Tetrahedron 67 (2011) 8679e8684
8683
J¼1.9 Hz, 1H), 6.65 (d, J¼2.0 Hz, 1H), 4.88 (d, J¼6.0 Hz, 2H), 4.76 (s,
H), 3.89 (s, 3H); (100.6 MHz, CDCl ) 168.2, 165.0, 163.7, 157.4,
53.2, 149.3, 141.7, 120.6, 114.9, 110.9, 106.0, 51.7, 45.0, 36.2.
solvent was evaporated. The crude product was purified by column
chromatography eluting with ethyl acetate/dichloromethane/hex-
2
1
d
C
3
ane (1:1:1) to give acyl azide 23a as a white solid (210 mg, 52%), mp
ꢀ
1
46e147 C; [Found: C, 45.31; H, 2.76; N, 19.85. C13
H
9
N
5
O
3
S
2
re-
(50% EtOAc/hexane) 0.60;
max (ATR) 3303, 3116, 2960, 2930, 2144, 1712, 1671, 1520, 1470,
4
.1.16. 2-({[(4-Oxo-4,6-dihydro-5H-thieno[2,3-c]pyrrol-5-yl)car-
quires C, 44.95; H, 2.61; N, 20.16%]; R
f
bonyl]amino}methyl)-3-thienoic acid (22a). H O (1 mL) was added
2
n
ꢂ1
H 3
; d (400 MHz, CDCl ) 9.12
to a stirred solution of the acyl chloride 20a (250 mg, 0.73 mmol) in
1446, 1273, 1248, 1168, 1141, 1070 cm
ꢀ
THF (25 mL) and stirred at 60 C for 2 h. The solvent and excess H
2
O
(br t, J¼6.1 Hz, 1H), 7.35 (d, J¼5.0 Hz, 1H), 7.32 (d, J¼5.4 Hz, 1H), 7.20
were evaporated. The crude product was purified by column
chromatography eluting with ethyl acetate to give carboxylic acid
(d, J¼5.0 Hz, 1H), 7.06 (d, J¼5.4 Hz, 1H), 4.95 (d, J¼6.3 Hz, 2H), 4.84
C 3
(s, 2H); d (100.6 MHz, CDCl ) 168.1, 165.1, 152.8, 152.4, 138.7, 131.1,
ꢀ
2
4
8
2
2a as a white solid (170 mg, 72%), mp 250e251 C; [Found: C,
129.2, 124.8, 124.1, 123.3, 120.5, 47.4, 37.9.
8.49; H, 3.30; N, 8.31. C13
H
10
N
2
O
4
S
2
requires C, 48.44; H, 3.13; N,
max (ATR) 3290, 3094, 3078,
979, 2579, 1696, 1631, 1526, 1465, 1441, 1419, 1395, 1359, 1263,
.69%]; R (5% MeOH/EtOAc) 0.73;
f
n
4.1.21. 2-({[(4-Oxo-4,6-dihydro-5H-furo[2,3-c]pyrrol-5-yl)carbonyl]
amino}methyl)-3-furoyl azide (23b). A solution of NaN
3
(0.68 g,
ꢂ1
1236, 1183, 1137, 1092, 1027 cm
;
d
H
(400 MHz, DMSO-d
6
) 12.95
10.5 mmol) in H O (5 mL) was added to a stirred solution of the acyl
2
ꢀ
(
br s, 1H), 9.04 (t, J¼6.2 Hz, 1H), 7.74 (d, J¼5.0 Hz, 1H), 7.40 (d,
J¼5.3 Hz, 1H), 7.35 (d, J¼5.3 Hz, 1H), 7.29 (d, J¼5.0 Hz, 1H), 4.89 (s,
H), 4.88 (d, J¼6.2 Hz, 2H); (100.6 MHz, DMSO-d ) 164.9, 164.3,
54.0, 152.3, 151.3, 137.8, 132.8, 129.5, 129.2, 123.6, 119.9, 48.0, 38.0.
chloride 20b (1.8 g, 5.83 mmol) in acetone (70 mL) at 2 C. Pre-
cipitation of inorganic salt was immediately observed. The resulting
2
1
d
C
6
mixture was stirred for 1 h and H
mixture was extracted with ethyl acetate (3ꢁ150 mL), the com-
bined organic layers were dried over MgSO and the solvent was
2
O (100 mL) was added. The
4
4
.1.17. 2-({[(4-Oxo-4,6-dihydro-5H-furo[2,3-c]pyrrol-5-yl)carbonyl]
evaporated. The crude product was purified by column chroma-
amino}methyl)-3-furoic acid (22b). The same procedure was used
as described above using acyl chloride 20b (400 mg, 1.30 mmol)
and crystallized from ethanol to give carboxylic acid 22b as a white
tography eluting with ethyl acetate/dichloromethane/hexane
(1:1:1) to give acyl azide 23b as a white solid (1.72 g, 92%), mp
ꢀ
121e122 C; [Found: C, 49.68; H, 2.98; N, 21.83. C13
H
9
N
5
O
5
requires
ꢀ
solid (260 mg, 70%), mp 206e207 C; [Found: C, 53.80; H, 3.51; N
C, 49.53; H, 2.88; N, 22.22%]; R
f
(50% EtOAc/hexane) 0.48;
n
max
9
.51. C13
H
10
N
2
O
6
requires C, 53.80; H, 3.47; N, 9.65%]; R
f
(5% MeOH/
(ATR) 3305, 3126, 2178, 2141, 1717, 1684, 1580, 1535, 1460, 1415,
ꢂ1
EtOAc) 0.60;
n
max (ATR) 3332, 3157, 3132, 1698, 1660, 1538, 1512,
1308, 1257, 1199, 1133, 1072 cm
H 3
; d (400 MHz, CDCl ) 8.87 (br t,
ꢂ1
1461, 1320, 1267, 1255, 1156, 1076 cm
;
d
H
(400 MHz, DMSO-d
6
)
J¼5.5 Hz, 1H), 7.57 (d, J¼2.0 Hz, 1H), 7.34 (d, J¼2.0 Hz, 1H), 6.67 (d,
1
2.87 (br s, 1H), 8.74 (t, J¼5.9 Hz, 1H), 8.01 (d, J¼1.8 Hz, 1H), 7.67 (d,
J¼1.9 Hz, 1H), 6.86 (d, J¼1.9 Hz, 1H), 6.69 (d, J¼1.8 Hz, 1H), 4.81 (s,
H), 4.76 (d, J¼5.9 Hz, 2H); (100.6 MHz, DMSO-d ) 169.5, 165.2,
64.7, 157.8, 152.8, 150.9, 142.7, 119.9, 115.3, 111.4, 106.1, 45.4, 36.3.
J¼2.0 Hz, 1H), 6.65 (d, J¼2.0 Hz, 1H), 4.90 (d, J¼6.0 Hz, 2H), 4.76 (s,
C 3
2H); d (100.6 MHz, CDCl ) 165.9, 165.7, 162.7, 156.4, 150.8, 150.0,
2
1
d
C
6
139.7, 118.2, 113.9, 108.3, 103.6, 42.7, 34.0.
4
.1.22. Methyl 2-({[(4-oxo-4,6-dihydro-5H-thieno[2,3-c]pyrrol-5-yl)
0
4
(
.1.18. 5,5 -Carbonyl-bis(5,6-dihydro-4H-thieno[2,3-c]pyrrol-4-one)
carbonyl]amino}-methyl)-3-thienylcarbamate (25a). The acyl azide
23a (200 mg, 0.58 mmol) was dissolved in dry benzene (30 mL) and
heated at reflux for 7 h. To this solution, dry MeOH (2 mL) was added
6a). The acyl chloride 20a (400 mg, 1.17 mmol) was dissolved in
toluene (25 mL) and heated at reflux for 48 h. After evaporation of
solvent the crude product was purified by column chromatography
ꢀ
and stirred at 50 C for 2 h. The solvent and excess MeOH were
(
silica gel, 40 g) eluting with dichloro-methane/ethyl acetate (3:2)
evaporated. The crude product was purified by column chromatog-
raphy (silica gel, 30 g) eluting with ethyl acetate/dichloromethane/
ꢀ
to give 6a as a white solid (175 mg, 49%), mp 260e262 C; [Found:
C, 51.43; H, 2.62; N, 8.93. C13
H
8
N
2
O
3
S
2
n
requires C, 51.30; H, 2.65; N,
max (ATR) 3120, 3092, 3072,
hexane (1:1:2) to give urethane 25a as a white solid (150 mg, 74%),
ꢀ
9
2
.20%]; R
f
(50% EtOAc/hexane) 0.53;
mp 211e213 C; [Found: C, 47.72; H, 3.60; N, 11.67. C14
H N O S
13 3 4 2
980, 1711, 1678, 1525, 1455, 1362, 1315, 1254, 1152, 1123,
requires C, 47.85; H, 3.73; N, 11.96%]; R
f
(50% EtOAc/hexane) 0.60;
ꢂ1
1088 cm
;
d
H
(400 MHz, CDCl
3
) 7.34 (d, J¼5.0 Hz, 2H), 7.20 (d,
n
max (ATR) 3294, 3105, 3091, 2958, 1743, 1692, 1674, 1581, 1537, 1493,
ꢂ1
J¼5.0 Hz, 2H), 5.01 (s, 4H);
d
C
(100.6 MHz, CDCl
3
) 161.9, 152.4, 149.2,
1437, 1274, 1232, 1148, 1041 cm
;
d
H
3
(400 MHz, CDCl ) 9.02 (br s,
þ
1
38.6, 130.9, 121.1, 47.9; HRMS found (MþNa) : 326.9846,
1H), 8.92 (br t, J¼5.4 Hz, 1H), 7.42 (br s, 1H), 7.35 (d, J¼5.0 Hz, 1H),
C
H
13 8
O
S
3 2
N
2
Na requires: 326.9869.
7.19 (d, J¼5.0 Hz,1H), 7.09 (d, J¼5.4 Hz), 4.84 (s, 2H), 4.45 (d, J¼6.4 Hz,
C 3
2H), 3.73 (s, 3H); d (100.6 MHz, CDCl ) 165.1, 154.7, 154.2, 152.5,
0
4
.1.19. 5,5 -Carbonyl-bis(5,6-dihydro-4H-furo[2,3-c]pyrrol-4-one)
138.5, 135.1, 131.2, 123.4, 123.3, 121.9, 120.5, 52.4, 47.5, 35.1.
(6b). The same procedure was used as described above using acyl
chloride 20b (100 mg, 0.32 mmol) to give the product 6b as a white
solid (45 mg, 51%), mp 200e202 C; [Found: C, 57.02; H, 2.85; N,
4.1.23. Methyl 2-({[(4-oxo-4,6-dihydro-5H-furo[2,3-c]pyrrol-5-yl)
ꢀ
carbonyl]amino}-methyl)-3-furylcarbamate (25b). The acyl azide
23b (500 g, 1.59 mmol) was dissolved in dry benzene (50 mL) and
reacted with MeOH as described above. Urethane 25b was isolated as
10.15. C13
8
H N
2
O
5
requires C, 57.36; H, 2.96; N, 10.29%]; R
f
(50%
EtOH/hexane) 0.47;
n
max (ATR) 3154, 3125, 1738, 1662, 1441, 1405,
ꢂ1
ꢀ
1308, 1267, 1131 cm
;
d
H
(400 MHz, CDCl
3
) 7.50 (d, J¼2.0 Hz, 2H),
awhite solid (410 g, 81%), mp 210e212 C;[Found: C, 52.37;H, 4.13; N,
6
.60 (d, J¼2.0 Hz, 2H), 4.83 (s, 4H); (100.6 MHz, CDCl
d
C
3
) 168.1,
13 3 6 f
12.85. C14H N O requires C, 52.67; H, 4.10; N,13.16%]; R (50% EtOAc/
þ
161.4, 149.4, 149.3, 120.5, 106.4, 45.5; HRMS found (MþNa) :
hexane) 0.45;
1503,1459,1317,1243,1141,1070cm
n
max (ATR) 3303, 3158, 3141,1741,1713,1664,1651,1530,
ꢂ1
2
95.0310, C13
8
H O
5
N
2
Na requires: 295.0331.
;
d
H
3
(400MHz,CDCl )8.80(brs,
1
H), 8.26 (br s, 1H,), 7.49 (d, J¼2.0 Hz, 1H), 7.16 (d, J¼2.0 Hz, 1H), 6.77
(br s, 1H), 6.58 (d, J¼2.0 Hz, 1H,), 4.67 (s, 2H), 4.30 (d, J¼6.0 Hz, 2H),
3.71 (s, 3H); (100.6 MHz, CDCl ) 168.2, 164.9, 154.7, 154.5, 149.4,
4
.1.20. 2-({[(4-Oxo-4,6-dihydro-5H-thieno[2,3-c]pyrrol-5-yl)car-
bonyl]amino}methyl)-3-thienyl azide (23a). A solution of NaN
0.162 g, 2.5 mmol) in H O (2 mL) was added to a stirred solution of
3
d
C
3
(
2
141.0, 138.9, 123.1, 120.5, 107.4, 106.0, 52.3, 45.0, 34.5.
the acyl chloride 20a (400 mg, 1.17 mmol) in acetone (30 mL) at
ꢀ
2
C. Precipitation of inorganic salt was immediately observed. The
O (100 mL) was
added. The mixture was extracted with ethyl acetate (3ꢁ50 mL),
the combined organic layers were dried over MgSO and the
4.1.24. Carbonyl-bis{[3-(amino)-2-furyl]methyl}-4-oxo-4,6-dihydro-
5H-furo[2,3-c]pyrrole-5-carboxamide (26b). The acyl azide 23b
(500 mg, 1.59 mmol) was dissolved in dry benzene (50 mL) and
heated at reflux for 7 h. Water (2 mL) was added to this solution and
resulting mixture was stirred for 1 h and then H
2
4