Category: 933-76-6

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.933-76-6,4,5-Dichloro-2-methylpyridazin-3(2H)-one,as a common compound, the synthetic route is as follows.,933-76-6

4,5-dichloro-2-methylpyridazin-3(2H)-one (200 mg, 1.1 17 mmol), 3-aminoazocan-2-one (155 mg, 1.09 mmol), N,N-diisopropylehtylamine (0.289 g, 2.23 mmol) and DMAc (1.3 mL) were charged in a sealable vial. The reaction was heated to 120 C for 2 hours. The reaction mixture was partitioned between EtOAc and NaHC03 (aq., sat.). The crude product was purified by flash chromatography (10% to 100% 1 :10:90 NH4OH:MeOH:DCM in DCM, 24g-silica gel column) to afford to sets of fractions containing regioisomers. The later eluting fractions (most polar isomer) was isolated after evaporation under reduced pressure to afford 3-((5-chloro-l -methyl-6- oxo-l ,6-dihydropyridazin-4-yl)amino)azocan-2-one (0.235 g, 0.84 mmol) in 77% yield. LCMS (ESI+): 285 / 287 (M+H, CI pattern).

The synthetic route of 933-76-6 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; GENENTECH, INC.; CONSTELLATION PHARMACEUTICALS, INC.; ALBRECHT, Brian, K.; BURDICK, Daniel, J.; COTE, Alexandre; DUPLESSIS, Martin; NASVESCHUK, Christopher, G.; TAYLOR, Alexander, M.; (117 pag.)WO2016/112298; (2016); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.933-76-6,4,5-Dichloro-2-methylpyridazin-3(2H)-one,as a common compound, the synthetic route is as follows.,933-76-6

b) Trifluoro-methanesulphonic acid 2-methyl-3-oxo-2,3-dihydro-pyridazin-4-yl ester (4b)[0242][0243]3.13 g (27.93 mmoles) of potassium tertbutylate is placed in 25 ml of tetrahydrofuran. At 0 C., a solution of 1.16 ml (27.93 mmoles) of methanol in 10 ml of tetrahydrofuran is added. The mixture is stirred at 0 C. for 10 min. This solution is added drop by drop to mixture cooled to 0 C. of 5 g (27.93 mmoles) of 4,5-dichloro-2-methyl-2H-pyridazin-3-one solubilised in 40 ml of tetrahydrofuran, the temperature of the medium remains below 3 C. during the addition. The mixture is stirred for 1 hour at 0 C., and for 3 hours at ambient temperature. The medium is taken up with dichloromethane and washed with water. After drying on Na2SO4, the organic phase is concentrated to dryness. The residue obtained is purified by flash chromatography (CH2Cl2-AcOEt: 95-5). 4.45 g of white solid is obtained (yield: 91%). TLC silica gel 60 F 254 Merck, CH2Cl2-AcOEt: 90-10, Rf=0.55. 3.37 g (19.3 mmoles) of this solid is placed in 150 ml of tetrahydrofuran in the presence of 2.7 ml (19.3 mmoles) of triethylamine and 0.67 g of 10% palladium on carbon. The medium is placed under hydrogen pressure (7 bar) and left under stirring for 48 hours. After filtering the reaction medium on celite, the filtrate is concentrated. The residue obtained is purified by flash chromatography (CH2Cl2-AcOEt gradient: 90-10 to 10-90). 2.35 g of white solid is obtained (yield: 86%). TLC silica gel 60 F 254 Merck, CH2Cl2-AcOEt: 50-50, Rf=0.17. 2.35 g (16.7 mmoles) of this solid is placed in 250 ml of water in the presence of 9.6 g (16.7 mmoles) of potassium hydroxide. The mixture is heated to 100 C. for 24 hours. The medium cooled to 0 C. is brought to pH 1-2 by adding an aqueous concentrated hydrochloric acid solution. After concentration to dryness, the residue is taken up with a dichloromethane/methanol mixture, the minerals are removed by filtration and the filtrate is concentrated to dryness. The residue obtained is purified by flash chromatography (CH2Cl2-MeOH: 95-5). 1.94 g of pink solid is obtained (yield: 92%). TLC silica gel 60 F 254 Merck, CH2Cl2-MeOH: 80-20, Rf=0.49. 1 g (7.92 mmoles) of this solid is placed in nitrogen in 15 ml of dichloromethane. At -9 C., 1.45 ml (10.3 mmoles) of triethylamine is added, followed by 1.8 ml (10.7 mmoles) of trifluoromethanesulphonic anhydride. After stirring for 20 min to -7 C., 5 ml of an aqueous 1N hydrochloric acid solution is added. The organic phase is washed with water, and with an aqueous 1% sodium bicarbonate solution, followed by a saturated NaCl solution. After drying on Na2SO4, the organic phases are concentrated to dryness. 1.9 g of intermediate 4b is obtained in pink solid form (yield: 93%).[0244]TLC silica gel 60 F 254 Merck, CH2Cl2-MeOH: 95-5, Rf=0.78.

933-76-6 4,5-Dichloro-2-methylpyridazin-3(2H)-one 120462, apyridazine compound, is more and more widely used in various fields.

Reference£º
Patent; PIERRE FABRE MEDICAMENT; Leroy, Isabelle; Dupont-Passelaigue, Elisabeth; Mialhe, Samuel; Junquero, Didier; Valeille, Karine; US2013/40928; (2013); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.933-76-6,4,5-Dichloro-2-methylpyridazin-3(2H)-one,as a common compound, the synthetic route is as follows.

Step A: Preparation of 5 -chloro-4-(2-methoxyethoxy)-2-methyl-3 (2H)-pyridazinone 4,5-Dichloro-2-methyl-3(2H)-pyridizinone (2.0 g, 11 mmol), 2-methoxyethanol (1.06 mL, 13.4 mmol) and sodium hydride (0.672 g, 16.8 mmol) were combined in 30 mL of dioxane and stirred at ambient temperature overnight. The reaction mixture was then poured over 100 mL of an ice/water mixture and extracted into ethyl acetate. The organic layer was washed with brine, dried (Mg504) and absorbed onto silica gel. Chromatography throughsilica gel eluting with a gradient of 0 to 100% ethyl acetate in hexanes provided 1.76 g of the title product as a white solid.1H NMR (500 MHz) oe 7.69 (s, 1H), 4.7 1-4.77 (m, 2H), 3.75 (s, 3H), 3.69-3.72 (m, 2H),3.39 (s, 3H)., 933-76-6

933-76-6 4,5-Dichloro-2-methylpyridazin-3(2H)-one 120462, apyridazine compound, is more and more widely used in various fields.

Reference£º
Patent; E. I. DU PONT DE NEMOURS AND COMPANY; STEVENSON, Thomas, Martin; WO2014/31971; (2014); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.933-76-6,4,5-Dichloro-2-methylpyridazin-3(2H)-one,as a common compound, the synthetic route is as follows.

933-76-6, Step 1: 4-bromo-5-chloro-2-methy]pyridazin-3(2H)-one 4,5-dichloro-2-methylpyridazin-3(2H)-one (180 mg, 1.01 mmol) was dissolved in 48% aqueous HBr (5 mL, 45 mmol). The reaction mixture was heated at 100 C for 16 hours. The reaction mixture was cooled down and basified up to pH = 8 with 1M aq. NaOH. The mixture was extracted with EtOAc. The organic layer was washed with brine, dried with Na2S04, filtered and evaporated under reduced pressure to afford a mixture of 4-bromo-5-chloro-2-methylpyridazin- 3(2H)-one and 5-bromo-4-chloro-2-methylpyridazin-3(2H)-one (280 mg, 1.253 mmol) in quantitative yield. LCMS (ESI+): 223 / 225 / 227 (M+H , Br, CI pattern). Step 2: 4-brorao-2-methyl-5-((l-methylazepan-3-yI)amiao)pyridaziii-3(2H)- The 4-bromo-5-chloro-2-methylpyridazin-3(2H)-one and 5-bromo-4-chloro-2-methylpyridazin- 3(2H)-one (280 mg, 1.253 mmol), l-methylazepan-3 -amine (0.209 g, 1.63 mmol), N-ethyl-N- isopropylpropan-2-amine (0.243 g, 1.88 mmol) and n-BuOH (1.5 mL) were charged in a microwave vial. The reaction was heated to 160 C for 60 min. The mixture of regioisomers was purified by flash chromatography (10% to 100% of 1 : 10:90 NH4OH:MeOH:DCM in DCM eluent gradient) to afford two sets of fractions. The later eluting fractions (most polar compound) were combined and evaporated under reduced pressure to afford 4-bromo-2-methyl- 5-((l -methylazepan-3-yl)amino)pyridazin-3(2H)-one (155 mg, 0.395 mmol) in 39% yield. lH NMR (400MHz, DMSO-d6) delta 7.77 (s, 1H), 6.20 (d, J= 8.8 Hz, 1H), 3.96 (br. s, 1 H), 3.57 (s, 3H), 2.55-2.75 (m, 3H), 2.34-2.45 (m, 1H), 2.37 (s, 3H), 1.31-1.74 (m, 6H). LCMS (ESI+): 315 / 317 (M+H, Br pattern).

The synthetic route of 933-76-6 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; GENENTECH, INC.; CONSTELLATION PHARMACEUTICALS, INC.; ALBRECHT, Brian, K.; BURDICK, Daniel, J.; COTE, Alexandre; DUPLESSIS, Martin; NASVESCHUK, Christopher, G.; TAYLOR, Alexander, M.; (117 pag.)WO2016/112298; (2016); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

933-76-6,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.933-76-6,4,5-Dichloro-2-methylpyridazin-3(2H)-one,as a common compound, the synthetic route is as follows.

Step C: Preparation of 4,5-dichloro-6-iodo-2-methyl-3(2H)-pyridazinone (0418) To 4,5-dichloro-2-methyl-3(2H)-pyridazinone (i.e. the product obtained in Example 1, Step B) (5.0 g, 27.9 mmol) dissolved in 80 mL tetrahydrofuran was added 2,2,6,6-bis(tetramethylpiperidine)zinc, magnesium chloride, lithium chloride complex 0.35M in toluene/tetrahydrofuran (i.e. Zn(TMP)2-LiCl-MgCl2 54 mL, 0.35 M in tetrahydrofuran/toluene) 18.75 mmol) over 3 to 5 min. The cloudy reaction mixture was stirred for 15 min and then iodine (8.5 g, 33.51 mmol) was added. The resulting mixture was stirred at ambient temperature for 15 min. The reaction mixture was quenched with aqueous sodium bisulfite solution (to remove excess iodine color), then water (200 mL) followed by 1 N aqueous hydrochloric acid (100 mL). The mixture was extracted with ethyl acetate (300 mL, then 200 mL). The resulting crude product which was purified by silica gel column chromatography eluting with 10% ethyl acetate in petroleum ether. A solid was triturated with diethyl ether and pentane, and the resulting pale yellow solid was dried (3 g). 1H NMR delta 3.83 (s, 3H).

933-76-6 4,5-Dichloro-2-methylpyridazin-3(2H)-one 120462, apyridazine compound, is more and more widely used in various fields.

Reference£º
Patent; E. I. DU PONT DE NEMOURS AND COMPANY; STEVENSON, Thomas Martin; SELBY, Thomas Paul; MARCUS, Kimberly Katherine; (118 pag.)WO2017/74992; (2017); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.933-76-6,4,5-Dichloro-2-methylpyridazin-3(2H)-one,as a common compound, the synthetic route is as follows.

General procedure: The respective 2-hydroxybenzenesulfonamide 5 (2 mmol) and 1,2-dihaloarene (1-halo-2-nitroarene) partner 9 (2 mmol) were combined in anhydrous DMF (7 mL) with freshly calcinated K2CO3 (829 mg, 6 mmol) and the mixture was kept, with stirring, at the temperature and for the time period indicated in Table 2. DMF was removed in vacuo and the residue was treated with water (10 mL), which caused a viscous oil to separate. It was extracted with CH2Cl2 (5 mL), the organic layer was separated, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel using an appropriate gradient of CH2Cl2 in hexanes as eluent., 933-76-6

As the paragraph descriping shows that 933-76-6 is playing an increasingly important role.

Reference£º
Article; Sapegin, Alexander; Panova, Valeria; Reutskaya, Elena; Smirnov, Alexey V.; Krasavin, Mikhail; Tetrahedron; vol. 72; 47; (2016); p. 7570 – 7578;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem