The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 699-89-8, name is 4,7-Dichlorothieno[2,3-d]pyridazine, A new synthetic method of this compound is introduced below., Computed Properties of C6H2Cl2N2S
A 250 mL, round-bottomed flask was equipped with a stir bar and reflux condenser. To the flask was added the product of step 4 (7.65 g, 37.3 mmol), 4-chloroaniline (4.76, 37.3 mmol) in EtOH (75 mL). The mixture was refluxed for 3 h. An orange solid precipitated from the reaction after 3 h. The reaction was cooled to rt and the solid was collected by filtration and washed with hexane. The desired 7-chloro-4-(4-chlorophenylamino)thieno[2,3-d]pyridazine was obtained (6.5 g, 21.9 mmol; 60% yield); mp= 139-142 C; ES MS (M+H)+= 297; TLC (Hexane- EtOAc, 60:40); Rf = 0.48.; To the dichloride from Example 8, step 4 (1.00 g, 4.90 mmol) was added p-chloroaniline (622 mg, 4.90 mmol) and absolute ethyl alcohol (10.0 mL). The mixture was refluxed at 95 C for 2 hrs and then cooled to room temperature. The yellow precipitate (2) that formed was filtered and washed with isopropyl alcohol, 4.0 N KOH, H2O, and then hexane. The filtrate (2) was then mixed 6-aminobenzothiazole (883 mg, 5.88 mmol) in 10 mL of n-butanol, and heated at 150 C overnight. The reaction was allowed to cool to room temperature before the solvent was removed by rotary evaporation. The residue was treated sequentially with aqueous 4.0 N KOH solution and extracted with dichloromethane (50 mL), dried (MgSO4), and the solvent evaporated. The crude product was purified by flash chromatography on silica gel using 95% dichloromethane/methanol as the eluent. The structure of the pure title compound was confirmed by LC/MS and NMR: TLC (30% EtOAc/Hexanes) Rf (3) = 0.20; 1H NMR (DMSO) delta 7.2 (dd, 3H), 7.38 (dd, 3H), 7.65 (d, 1H), 8.0 (d, 1H), 8.45 (d, 1H), 8.8 (s, 1H); LC/MS m/z 410 rt = 4.21 min.; Equal equivalents of dichloride (1) and M-NH2 are refluxed in the appropriate amount of absolute ethanol at 95 C for 2 hrs. The reaction mixture is allowed to cool to room temperature and the precipitate (2) that forms is filtered and washed sequentially with isopropyl alcohol, 4.0 N KOH, H2O, and hexane, and then dried. The filtrate (2) is then reacted with 1.2 equivalent of Q-NH2 in an appropriate amount of n-butyl alcohol at 150 C for 10 hrs. The reaction is cooled to room temperature before the solvent is evaporated under reduced pressure. The residue is treated with aqueous 4.0 N KOH solution and extracted with dichloromethane. The organic layer is dried (MgSO4) and evaporated. The crude product (3) is purified by preparative thin layer chromatography (TLC) or flash chromatography on silica gel using dichloromethane/methanol (95:5) as the eluent. Final product is confirmed by LC/MS and/or NMR. The invention compounds of Examples 23 – 25, 48, and 76-80 as shown in the below table were prepared by method A-1.
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; BAYER CORPORATION; EP1228063; (2009); B1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics