Thienopyridazines and Related Compounds
1125
Ethyl 3-amino-7,8-diphenylfuro[20,30:4,5]thieno[2,3-c]pyridazine-2-caboxylate (9; C23H17N3O3S)
A) A suspension of 4.15 g 7 (0.01 mol) in sodium ethoxide solution (1.0 g sodium in 100 cm3 abs.
ethanol) was heated under re¯ux for 10 min. The solid product separating on cooling was collected
and recrystallized from ethanol to give 9.
Yield: 3.5 g (84%); m.p.: 252±254ꢀC; IR: ꢀmax 3450, 3330 (NH2), 1660 (C=O) cmꢁ1; 1H NMR
(DMSO-d6): ꢁ 7.1±7.6 (m, 10H, ArH), 5.9 (s, 2H, NH2), 4.1±4.4 (q, 2H, OCH2), 1.2±1.5 (t, 3H,
CH3) ppm; MS: m/z (%) 417 (M 2, 13), 416 (M 1, 37), 415 (M , 88), 414 (M -H, 84), 413
(M -2H, 100), 385 (M -H-C2H5, 17).
B) To a mixture of 3.3 g 4f (0.01 mol) and 1.23 g ethyl chloroacetate (0.01 mol) in 20 cm3 DMF,
2.76 g anhydrous K2CO3 (0.02 mol) was added. The reaction mixture was heated on a water bath for
10 h, cooled, and diluted with 15 cm3 H2O. The solid precipitated was collected and crystallized
from ethanol to give 9 in 70% yield (2.9 g). The products obtained by the two synthetic routes are
identical in all aspects.
3,4-Dihydro-6,7-diphenyl-4-oxopyrimido[400,500:40,50]furo[20,30:4,5]thieno[2,3-c]pyridazine
(10; C22H12N4O2S)
A solution of 0.41 g 9 (0.001 mol) in 15 cm3 formamide was heated under re¯ux for 4 h. The
precipitate separating after cooling was collected and recrystallized from DMF to give 10.
Yield: 0.3 g (70%); m.p.: >300ꢀC; IR: ꢀmax 3200±2400 (br, NH), 1660 (C=O) cmꢁ1; MS: m/z
(%) 396 (M , 35), 394 (M -2H, 80), 481 (M -NH, 40), 380 (M -O, 100), 370 (M -CN, 85).
3-Amino-7,8-diphenylfuro[20,30:4,5]thieno[2,3-c]pyridazine-2-carbohydrazide (11; C21H15N5O2S)
A suspension of 4.15 g 9 (0.01 mol) in 10 cm3 hydrazine hydrate 99% (0.2 mol) was heated under
re¯ux for 3 h. The reaction mixture was titurated with 25 cm3 ethanol and left to cool. The solid
which formed was collected and recrystallized from dioxane to give 11.
Yield: 3.5 g (87%); m.p.: 295±297ꢀC; IR: ꢀmax 3420, 3300, 3200, 3150 (2NH2, NH), 1620
(C=O) cmꢁ1
.
3-Amino-7,8-diphenylfuro[20,30:4,5]thieno[2,3-c]pyridazine-2-carbonylazide (12; C21H12N6O2S)
3.5 cm3 chilled sodium nitrite solution (10%, 0.005 mol) was added dropwise to a solution of 2.0 g 11
(0.005 mol) in 10 cm3 glacial acetic acid at 5±10ꢀC during 5 min. with stirring. The reaction mixture
was allowed to stand at room temperature for 1 h and then diluted with 25 cm3 H2O. The precipitate
which formed was collected, dried in air, and used in the next step without puri®cation.
Yield: 1.6 g (77%); m.p.: 230ꢀC (dec.); IR: ꢀmax 3450, 3300 (NH2), 2130 (N3), 1660
(C=O) cmꢁ1
.
5,6-Diphenyl-1H-imidazolo[400,500:40,50]furo[20,30:4,5]thieno[2,3-c]pyridazine-2(3H)-one
(14; C21H12N4O2S)
A solution of 0.41 g 12 (0.001 mol) in 15 cm3 dry toluene was heated under re¯ux for 3 h. The
precipitate separating upon cooling was collected and recrystallized from DMF to give 14.
Yield: 0.2 g (52%); m.p.: 293±295ꢀC; IR: ꢀmax 3300±3100 (2NH), 1680 (C=O) cmꢁ1
.
4,5-Diphenyl-3-hydroxythieno[2,3-c]pyridazine (16; C18H12N2OS)
A solution of 3.8 g 4g (0.01 mol) in 40 cm3 ethanolic sodium hydroxide solution (7%) was
heated under re¯ux for 5 h and left to cool. The reaction mixture was diluted with 40 cm3 H2O