Bis(iminophosphorane) in Heterocyclic Synthesis
12H), 1.08-1.26 (m, 32H), 3.00 (t, J ) 7.2 Hz, 8H), 7.26-7.42
(m, 10H). MS m/z 738 (M+, 100), 667 (20), 554 (12), 452 (38),
287 (13), 119 (49). Anal. Calcd for C44H62N6O2S: C, 71.51; H,
8.46; N, 11.37. Found: C, 71.62; H, 8.35; N, 11.39.
the synthesis of many biologically and pharmaceutically
active thienodipyrimidinone derivatives.
Experimental Section
2,7-Di(diisopropylamino)-3,6-diphenylthieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-dione (6f). White crystals (yield
72%); mp >300 °C. IR (KBr) 1717 (CdO), 1526, 1498, 1127,
Diethyl 2,5-Bis(triphenylphosphoranylideneamino)-
thiophen-3,4-dicarboxylate (3). 3 was prepared from diethyl
2,5-diaminothiophene-3,4-carboxylate3c according to a litera-
ture report.7 Deep yellow crystals (yield 70%); mp 200-202
°C (lit.7 mp 201-203 °C).
1
698 cm-1. H NMR (CDCl3, 400 MHz) δ 1.07 (d, J ) 6.8 Hz,
24H), 3.51-3.57 (m, 4H), 7.23-7.40 (m, 10H). 13C NMR
(CDCl3, 100 MHz) δ 21.2 (8), 49.8 (4), 112.3 (2), 127.2 (2), 128.1
(4), 129.3 (4), 138.8 (2), 154.8 (2), 157.2 (2), 160.4 (2). MS m/z
570 (M+, 56), 527 (41), 470 (18), 368 (27), 250 (12), 119 (58),
43 (100). Anal. Calcd for C32H38N6O2S: C, 67.34; H, 6.71; N,
14.72. Found: C, 67.25; H, 6.83; N, 14.75.
2,7-Diaminothieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-
diones (6). To a solution of bis(iminophosphorane) 3 (2.33 g,
3 mmol) in dry methylene dichloride (15 mL) was added
aromatic isocyanate (6 mmol) under nitrogen at room tem-
perature. After the reaction mixture was left to stand for 8-12
h at 0-5 °C, the solvent was removed reduced pressure and
ether/petroleum ether (1:2, 20 mL) was added to precipitate
triphenylphosphine oxide. After filtration the solvent was
removed to give bis(carbodiimide) 4, which was used directly
without further purification. To the solution of 4 prepared
above in methylene dichloride (15 mL) was added dialkylamine
(6 mmol). After the reaction mixture was allowed to stand for
0.5-6 h, the solvent was removed and anhydrous ethanol (10
mL) with several drops of EtONa in EtOH was added. The
mixture was stirred for 1-6 h at room temperature. The
solution was then concentrated under reduced pressure and
the residual was recrystallized from ethanol to give 2,7-
diaminothieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-diones 6.
2,7-Di(diethylamino)-3,6-diphenylthieno[2,3-d:5,4-d′]-
dipyrimidine-4,5(3H,6H)-dione (6a). White crystals (yield
85%); mp >300 °C. IR (KBr) 1715 (CdO), 1536, 1508, 1286,
2,7-Di(4-morpholinyl)-3,6-di(4-methylphenyl)thieno-
[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-dione (6g). White
crystals (yield 87%); mp >300 °C. IR (KBr) 1717 (CdO), 1535,
1
1505, 1113, 952 cm-1. H NMR (CDCl3, 400 MHz) δ 2.38 (s,
6H), 3.13 (t, J ) 4.4 Hz, 8H), 3.43 (t, J ) 4.4 Hz, 8H), 7.21 (s,
8H). MS m/z 570 (M+, 82), 539 (10), 484 (21), 368 (34), 203
(71), 91 (100). Anal. Calcd for C30H30N6O4S: C, 63.14; H, 5.30;
N, 14.73. Found: C, 63.21; H, 5.36; N, 14.86.
3,6-Di(4-chlorophenyl)-2,7-di(1-piperidinyl)thieno[2,3-
d:5,4-d′]dipyrimidine-4,5(3H,6H)-dione (6h). White crys-
tals (yield 81%); mp >300 °C. IR (KBr) 1712 (CdO), 1535,
1489, 1251, 944 cm-1 1H NMR (CDCl3 + TFA, 400 MHz) δ
.
1.40-1.56 (m, 12H), 3.31 (t, J ) 5.6 Hz, 8H), 7.32-7.57 (m,
8H). MS m/z 608/606 (M+, 60/100), 522 (7), 467 (11), 386 (17),
221 (13), 165 (8). Anal. Calcd for C30H28Cl2N6O2S: C, 59.31;
H, 4.65; N, 13.83. Found: C, 59.25; H, 4.46; N, 13.91.
2,7-Diaryloxythieno[2,3-d:5,4-d′]dipyrimidine-4,5-
(3H,6H)-diones (6). To the solution of 4 prepared above in
CH3CN (15 mL) was added substituted phenol (6 mmol) and
solid K2CO3 (0.14 g, 1.0 mmol). The mixture was stirred for
6-8 h at 40-50 °C and filtered, the filtrate was condensed,
and the residual was recrystallized from methylene dichloride/
petroleum ether to give 2,7-diaryloxythieno[2,3-d:5,4-d′]dipy-
rimidine-4,5(3H,6H)-diones 6.
1
700 cm-1. H NMR (CDCl3, 400 MHz) δ 0.84 (t, J ) 7.2 Hz,
12H), 3.11 (q, J ) 7.2 Hz, 8H), 7.26-7.40 (m, 10H). 13C NMR
(CDCl3, 100 MHz) δ 12.5 (4), 45.0 (4), 112.4 (2), 127.7 (2), 128.6
(4), 129.1 (4), 138.1 (2), 156.0 (2), 157.0 (2), 161.1 (2). MS m/z
514 (M+, 100), 486 (11), 396 (22), 340 (35), 175 (26), 119 (38).
Anal. Calcd for C28H30N6O2S: C, 65.35; H, 5.88; N, 16.33.
Found: C, 65.27; H, 5.94; N, 16.57.
2,7-Di(4-chlorophenoxy)-3,6-diphenylthieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-dione (6i). White crystals (yield
82%); mp >300 °C. IR (KBr) 1729 (CdO), 1561, 1484, 1211,
2,7-Di(di-n-propylamino)-3,6-diphenylthieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-dione (6b). White crystals (yield
76%); mp 288-289 °C. IR (KBr) 1718 (CdO), 1533, 1507, 1244,
1
941 cm-1. H NMR (CDCl3, 400 MHz) δ 7.04-7.44 (m, 18H).
1
738 cm-1. H NMR (CDCl3, 400 MHz) δ 0.73 (t, J ) 7.2 Hz,
MS m/z 626/624 (M+, 76/100), 497 (88), 378 (5), 119 (29), 77
(56). Anal. Calcd for C32H18Cl2N4O4S: C, 61.45; H, 2.90; N,
8.96. Found: C, 61.49; H, 2.78; N, 8.80.
12H), 1.24-1.30 (m, 8H), 2.98 (t, J ) 7.6 Hz, 8H), 7.26-7.42
(m, 10H). 13C NMR (CDCl3, 100 MHz) δ 11.2 (4), 20.6 (4), 52.5
(4), 112.1 (2), 127.6 (2), 128.4 (4), 128.9 (4), 137.9 (2), 155.9
(2), 156.8 (2), 160.9 (2). MS m/z 570 (M+, 72), 541 (16), 470
(25), 368 (50), 203 (46), 119 (100). Anal. Calcd for C32H38-
N6O2S: C, 67.34; H, 6.71; N, 14.72. Found: C, 67.56; H, 6.88;
N, 14.64.
2,7-Di(4-bromophenoxy)-3,6-diphenylthieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-dione (6j). White crystals (yield
73%); mp >300 °C. IR (KBr) 1730 (CdO), 1560, 1484, 1209,
1
939 cm-1. H NMR (CDCl3, 400 MHz) δ 7.00-7.45 (m, 18H).
MS m/z 716/714/712 (M+, 66/100/56), 543 (96), 514 (10), 119
(30), 77 (56). Anal. Calcd for C32H18Br2N4O4S: C, 53.80; H,
2.54; N, 7.84. Found: C, 53.93; H, 2.36; N, 7.54.
2,7-Di(di-n-butylamino)-3,6-diphenylthieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-dione (6c). White crystals (yield
82%); mp 224-226 °C. IR (KBr) 1719 (CdO), 1532, 1507, 1229,
1
737 cm-1. H NMR (CDCl3, 400 MHz) δ 0.83 (t, J ) 7.2 Hz,
2,7-Di(4-methylthiophenoxy)-3,6-diphenylthieno[2,3-
d:5,4-d′]dipyrimidine-4,5(3H,6H)-dione (6k). White crys-
tals (yield 84%); mp >300 °C. IR (KBr) 1731 (CdO), 1560,
12H), 1.10-1.24 (m, 16H), 3.01 (t, J ) 7.2 Hz, 8H), 7.26-7.41
(m, 10H). 13C NMR (CDCl3, 100 MHz) δ 13.6 (4), 19.9 (4), 29.4
(4), 50.5 (4), 112.1 (2), 127.5 (2), 128.3 (4), 128.9 (4), 137.9 (2),
155.9 (2), 156.8 (2), 160.9 (2). MS m/z 626 (M+, 74), 570 (8),
498 (11), 396 (41), 231 (27), 119 (79), 57 (100). Anal. Calcd for
C36H46N6O2S: C, 68.98; H, 7.40; N, 13.41. Found: C, 68.85;
H, 7.16; N, 13.63.
1
1484, 1209, 939 cm-1. H NMR (CDCl3, 400 MHz) δ 2.48 (s,
6H), 7.04-7.46 (m, 18H). 13C NMR (CDCl3, 100 MHz) δ 21.3
(2), 114.7 (2), 119.2 (2), 123.3 (4), 128.0 (4), 129.9 (4), 131.9
(2), 132.6 (4), 138.8 (2), 150.6 (2), 154.1 (2), 155.7 (2), 159.7
(2). MS m/z 648 (M+, 41), 529 (14), 509 (68), 139 (45), 77 (100).
Anal. Calcd for C34H24N4O4S3: C, 62.95; H, 3.73; N, 8.64.
Found: C, 62.72; H, 3.87; N, 8.84.
2,7-Di(di-n-pentylamino)-3,6-diphenylthieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-dione (6d). White crystals (yield
71%); mp 189-190 °C. IR (KBr) 1718 (CdO), 1532, 1508, 1458,
2,7-Di(4-bromophenoxy)-3,6-di(4-methylphenyl)thieno-
[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-dione (6l). White crys-
tals (yield 70%); mp >300 °C. IR (KBr) 1729 (CdO), 1562,
1
737 cm-1. H NMR (CDCl3, 400 MHz) δ 0.85 (t, J ) 7.2 Hz,
12H), 1.04-1.28 (m, 24H), 3.00 (t, J ) 7.6 Hz, 8H), 7.26-7.42
(m, 10H). MS m/z 682 (M+, 64), 625 (6), 424 (28), 354 (8), 259
(14), 119 (56), 43 (100). Anal. Calcd for C40H54N6O2S: C, 70.35;
H, 7.97; N, 12.30. Found: C, 70.18; H, 7.91; N, 12.47.
1481, 1212, 945 cm-1 1H NMR (CDCl3 + TFA, 400 MHz) δ
.
2.46 (s, 6H), 7.03-7.58 (m, 16H). MS m/z 744/742/740 (M+,
13/23/11), 571 (9), 133 (50), 39 (100). Anal. Calcd for C34H22-
Br2N4O4S: C, 55.00; H, 2.99; N, 7.55. Found: C, 55.14; H, 2.92;
N, 7.48.
2,7-Di(di-n-hexylamino)-3,6-diphenylthieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-dione (6e). White crystals (yield
67%); mp 169-170 °C. IR (KBr) 1718 (CdO), 1534, 1508, 1466,
2,7-Di(4-methylphenoxy)-3,6-di(3-methylphenyl)thieno-
[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-dione (6m). White
1
737 cm-1. H NMR (CDCl3, 400 MHz) δ 0.87 (t, J ) 7.2 Hz,
J. Org. Chem, Vol. 69, No. 24, 2004 8369