Category: 1837-55-4

1837-55-4, 3,5-Dichloropyridazine is a pyridazine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

In analogy to the preparation of the intermediate 8-1 (step 1) from tert-butyl N- [(lR,5S,8S)-3-azabicyclo[3.2.1]octan-8-yl]carbamate (2.00 g, 8.84 mmol) and 3,5- dichloropyridazine (2.0 g, 13.4 mmol) in a sealed tube at 90 C using EtOH as solvent in the presence of Et3N (3.63 g, 5.0 mL, 35.9 mmol), tert-butyl N-[(lR,5S,8S)-3-(6-chloropyridazin-4- yl)-3-azabicyclo[3.2.1]octan-8-yl]carbamate (1.71 g, 54%) was obtained as a white solid. MS (ES+) m/z: 339.2 [(M+H)+]., 1837-55-4

As the paragraph descriping shows that 1837-55-4 is playing an increasingly important role.

Reference£º
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; BARTELS, Bjoern; JAKOB-ROETNE, Roland; LIMBERG, Anja; NEIDHART, Werner; RATNI, Hasane; REUTLINGER, Michael; SARIE, Jerome Charles; VASTAKAITE, Greta; (61 pag.)WO2018/83050; (2018); 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.1837-55-4,3,5-Dichloropyridazine,as a common compound, the synthetic route is as follows.

INTERMEDIATE 53 5-(3-Bromo-4-fluoro-lH-pyrazol-l-yl)-3-chloropyridazine To a solution of 3-bromo-4-fluoro-lH-pyrazole (100 mg, 0.606 mmol) in anhydrous DMF (1 mL) added potassium fert-butoxide (68 mg, 0.606 mmol) slowly at room temperature. The mixture was stirred at room temperature for 10 min, followed by the addition of 3,5-dichloropyridazine (90 mg, 0.606 mmol) in DMF (1 mL). The resulting mixture was stirred at 100 C for 1 h. The mixture was cooled to room temperature, quenched with water (10 mL) and extracted with EtOAc (40 mL x 3). The organic layer was collected and dried over Na2S04. The solvent was removed in vacuo to give the crude product. This was purified by flash chromatography (ISCO Combiflash, 10 g, Biotage Si column, -30 mL/min, 100% hexanes 5 min, gradient to 100% EtOAc in hexanes 15 min) to afford 5-(3-bromo-4-fluoro-lH-pyrazol-l-yl)-3- chloropyridazine. LCMS calc. = 278.93; found = 278.82 (M+H)+., 1837-55-4

1837-55-4 3,5-Dichloropyridazine 19959687, apyridazine compound, is more and more widely used in various fields.

Reference£º
Patent; MERCK SHARP & DOHME CORP.; MOCHIDA PHARMACEUTICAL CO., LTD.; SMITH, Cameron, James; TAN, John, Qiang; ZHANG, Ting; BALKOVEC, James; GREENLEE, William, John; GUO, Liangqin; XU, Jiayi; CHEN, Yi-heng; CHEN, Yili; CHACKALAMANNIL, Samuel; HIRABAYASHI, Tomokazu; NAGASUE, Hiroshi; OGAWA, Kouki; WO2014/120346; (2014); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

1837-55-4, 3,5-Dichloropyridazine is a pyridazine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

[01040] Sodium methoxide (5.84 g, 0.108 mol) was added to a stirred solution of 3,5-dichloropyridazine (8 g, 0.054 mol) in 350 mL of THF at 0C. After the addition, the mixture was stirred at room temperature for 16 h. The mixture was quenched with water (100 mL), extracted with EA (300 mL X 2). The combined organic solvents were dried over anhydrous Na2S04, concentrated and purified by silica gel chromatography (0-40% EtO Ac/petroleum ether) which gave 1.5 g of 5-chloro-3-methoxypyridazine as yellow solid (17% yield). LCMS: m/z 145.1 [M+H]+; = 1.42 min., 1837-55-4

As the paragraph descriping shows that 1837-55-4 is playing an increasingly important role.

Reference£º
Patent; SKYHAWK THERAPEUTICS, INC.; LUZZIO, Michael; MCCARTHY, Kathleen; HANEY, William; (470 pag.)WO2019/28440; (2019); 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.1837-55-4,3,5-Dichloropyridazine,as a common compound, the synthetic route is as follows.

A solution of 3,5-dichloropyridazine (2.00 g, 13.4mmol), phenylboronic acid (1.64 g, 13.4 mmol), Pd(OAc)2 (0.301 g, 1.34 mmol), 1,2,3,4,5-pentaphenyl-1?-(di-tert-butylphosphino)ferrocene (1.906 g, 2.685 mmol), KF (1.947 g, 33.56mmol), dioxane (50 mL), and water (12 mL) was stirred at reflux for 15 h under N2. The mixturewas diluted with EtOAc, washed with brine, dried over anhydrous Na2SO4, and concentrated to dryness. The residue was purified by flash column chromatography to give the title Compound (1.53 g, 59.8% yield) as white solid. MS (ESI): mass calcd. for C10H7C1N2, 190.63; m/z found, 190.0 [M+Hj., 1837-55-4

The synthetic route of 1837-55-4 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; JANSSEN PHARMACEUTICA NV; ARORA, Nidhi; BACANI, Genesis M.; BARBAY, Joseph Kent; BEMBENEK, Scott D.; CAI, Min; CHEN, Wei; DECKHUT, Charlotte Pooley; EDWARDS, James P.; GHOSH, Brahmananda; KREUTTER, Kevin; LI, Gang; TICHENOR, Mark S.; VENABLE, Jennifer D.; WEI, Jianmei; WIENER, John J. M.; WU, Yao; XIAO, Kun; ZHANG, Feihuang; ZHU, Yaoping; (528 pag.)WO2017/100662; (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.1837-55-4,3,5-Dichloropyridazine,as a common compound, the synthetic route is as follows.

To a 0.5 – 2.0 mL microwave vial charged with (S)-5,5-dimethyl-4- phenyl-3-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)oxazolidin-2-one (Intermediate J) (0.240 g, 0.610 mmol) and 3,5-dichloropyridazine (commercially available from ACES Pharma, Princeton, NJ) (0.100 g, 0.671 mmol) were added dioxane (1.220 mL), and 2 M Na2C03 (1.220 mL). Nitrogen was bubbled through the resulting suspension and then Pd(PPh3)4 (0.071 g, 0.061 mmol) was added. The resulting mixture was irradiated at 100C for 30 minutes. LC-MS indicated the formation of product as a major species (two close peaks with product mass, likely isomers) along with other impurities with consumption of starting material. The dark suspension was diluted with water, transferred to a separatory funnel, and extracted with EtOAc (2x). The combined organic layers were dried with Na2S04, filtered, and dried under reduced pressure. The residual material was purified with a 40 g HP 15 muiotaeta spherical silica column (Interchim) ramping EtOAc in heptane from 0 – 100% leading to isolation of product (primarily one isomer) as the major species with 10- 15% impurity. (S)-3-(4-(5-Chloropyridazin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin- 2-one (0.058 g, 0.153 mmol, 25.02 % yield) was obtained as a white solid. Note: the regiochemistry of the product was not confirmed, but it was assumed that the major product would result from the more reactive chloride), m/z (ESI) 380.1 (M+H)+., 1837-55-4

As the paragraph descriping shows that 1837-55-4 is playing an increasingly important role.

Reference£º
Patent; AMGEN INC.; BREGMAN, Howard; BUCHANAN, John, L.; CHAKKA, Nagasree; DIMAURO, Erin; GUNAYDIN, Hakan; GUZMAN PEREZ, Angel; HUA, Zihao; HUANG, Hongbing; HUANG, Xin; MARTIN, Matthew, W.; PATEL, Vinod; WO2013/134079; (2013); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

1837-55-4, 3,5-Dichloropyridazine is a pyridazine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 95: 5-[(3R)-3-(Methylamino)pyrrolidin-1-yl]-N-(2- methylpropyl)pyridazin-3-arnine. [1 -(delta-Chloro-pyridazin-^yO-pyrrolidin-S-yO-methyl-carbamic acid tert-butyl ester. A solution of 3,5-dichloropyridazine (149 mg, 1.0 mmol) in THF (3 ml_) at 23 0C was treated with (RJ-methyl-pyrrolidin-S-yl-carbamic acid tert-butyl ester (440 mg, 2.2 mmol) and the reaction stirred at 23 0C for 18 h. The reaction diluted with EtOAc (30 ml) and solution washed with water (2 x 5 ml) and combined organic solution dried and concentrated and crude material purified on 16 g SiO2 (O to 30% EtOAc : Hex) to yield 283 mg (91 % yield) of the desired regioisomer and 17 mg (5% yield) of the undesired regioisomer. MS (ESI): mass calcd. for Ci4H2iCIN4O2, 312.5 m/z found, 313.5 [M+H]+. [1 -(delta-lsobutylamino-pyhdazin^-yO-pyrrolidin-S-yO-methyl-carbamic acid tert- butyl ester. A solution of [1-(6-chloro-pyhdazin-4-yl)-pyrrolidin-3-yl]-methyl- carbamic acid tert-butyl ester (32 mg, 0.1 mmol) in isobutylamine (1.0 ml) in a sealed tube was heated to 120 0C for 72 h. The resulting solution was purified directly on 12 g SiO2 (0 to 5% NH3/Me0H:CH2CI2) to yield 20 mg (55% yield). lsobutyl-[5-(3-methylamino-pyrrolidin-1 -yl)-pyhdazin-3-yl]-amine dihydrochlohde. To a stirring solution of [1-(6-isobutylamino-pyhdazin-4-yl)- pyrrolidin-3-yl]-methyl-carbamic acid tert-butyl ester (19 mg, 0.06 mmol) in 96% formic acid (0.5 ml_) was added 0.05 ml of aqueous 6N HCI. The mixture was stirred for 2 hr, diluted with MeOH and concentrated under reduced pressure (repeat 3X) to give the desired product as a white solid (101 mg, >99%). MS (ESI): mass calcd. for Ci3H23N5, 249.4 m/z found, 250.2 [M+H]. 1H NMR (400 MHz, CD3OD): 8.12 (d, J = 2.5, 1 H), 6.08 (s, 1 H), 4.1 1 – 4.01 (m, 1 H), 4.04 – 3.47 (m, 4H), 3.35 (s, 1 H), 3.15 (d, J = 7.0, 2H), 2.82 (s, 3H), 2.65 – 2.53 (m, 1 H), 2.43 – 2.31 (m, J = 5.6, 1 H), 1.96 (dt, J = 13.4, 6.7, 1 H), 1.03 (d, J = 6.7, 6H)., 1837-55-4

As the paragraph descriping shows that 1837-55-4 is playing an increasingly important role.

Reference£º
Patent; JANSSEN PHARMACEUTICA NV; WO2009/152325; (2009); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

1837-55-4, 3,5-Dichloropyridazine is a pyridazine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Synthesis of tert-butyl 5-(5-chlororyridazin-3-yl)thiorhene-2-carboxylateA solution of 3,5-dichloropyridazine (2.00 g, 13.4 mmol) and tert-butyl 5-(tributylstannyl)thiophene-2-carboxylate (6.35 g, 13.4 mmol, synthesis see above) in 1,4-dioxane (25 mL) was degassed with Ar. CsF(6.12 g, 40.3 mmol), CuCl (0.133 g, 1.34 mmol) and PdCl2(dppf) (0.491 g, 0.671 mmol) were added andthe mixture was heated at7O C for2 h. KF (3.12 g, 53.7 mmol) in 50 mL water was added and themixture was stirred at RT for 2 h. The mixture was filtered over Celite and rinsed with DCM (15 mL) and brine (15 mL). The organic layer was dried over Na2SC4, filtered and concentrated in vacuo. FC (EtOAc/ DCM 0:1 – 1:1) afforded tert-butyl 5-(5-chloropyridazin-3-yl)thiophene-2-carboxylate (2.14 g, 6.65 mmol, 49%). LCMS: calc. for [M+H] = 297.04, found 297.0.

1837-55-4, The synthetic route of 1837-55-4 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; GRUeNENTHAL GMBH; NARDI, Antonio; RATCLIFFE, Paul; CRAAN, Tobias; HERTRAMPF, Thorsten; LESCH, Bernhard; KIME, Robert; STEINHAGEN, Henning; WO2015/161928; (2015); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

1837-55-4, 3,5-Dichloropyridazine is a pyridazine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

131.1 3-chloro-5-methoxypyridazine To a solution of 3,5-dichloropyridazine (300 mg) in MeOH (2 mL) was added a 5.4 M solution of sodium methoxide in MeOH (0.410 mL) and the reaction mixture was stirred for 1 h at 90 C. It was quenched with H2O and extracted with EtOAc. The organic phase was washed with a 5% solution of KHSO4, a sat. solution of NaHCO3 and brine, dried over MgSO4 and concentrated in vacuo to give the crude titled compound as an orange solid. 1H NMR ((CD3)2SO) delta: 9.01 (d, J=2.4 Hz, 1H), 7.55 (d, J=2.4 Hz, 1H), 3.96 (s, 3H), 1837-55-4

As the paragraph descriping shows that 1837-55-4 is playing an increasingly important role.

Reference£º
Patent; Actelion Pharmaceuticals Ltd.; Hilpert, Kurt; Hubler, Francis; Murphy, Mark; Renneberg, Dorte; US2014/73651; (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.1837-55-4,3,5-Dichloropyridazine,as a common compound, the synthetic route is as follows.

Example 413: (f?)-5-(3-(methylamino)pyrrolidin-1-yl)-N-(1- adamantyl)pyridazin-3-amine dihydrochloride. (R)-tert-butyl 1-(6-chloropyridazin-4-yl)pyrrolidin-3-ylcarbamate. A solution of 3,5-dichloropyridazine (4.47g, 30mmol), (R)-tert-butyl pyrrolidin- 3-ylcarbamate (5.59g, 30mmol) and thethylamine (8.1 g, 80mmol) in THF (50 mL) was stirred at ambient temperature for 20 hrs. The solvent was removed under reduced pressure and the residue was purified by column chromatography to afford the desired product (5.4 g, 60%) as a colorless solid. LC-MS: m/z = 299.2 [M+H+]+. (f?)-tert-butyl-1-(6-chloropyridazin-4-yl)pyrrolidin-3-yl(methyl) carbamate. A solution of (R)-tert-butyl 1-(6-chloropyhdazin-4-yl)pyrrolidin-3-ylcarbamate (3.6g, 12.05mmol) in N,N-dimethylformamide (DMF, 4OmL) was added into a suspension of 60% sodium hydride (0.58 g, 14.5 mmol) in DMF (40 mL) at 0 0C. The mixture was stirred at 0 0C for further 30 min then lodomethane (2.06 g, 14.5 mmol) was added into the mixture and the resulting reaction was stirred for further 3h at ambient temperature. Water (100 mL) was added and the mixture was extracted with dichloromethane. The combined organic layer was dried over Na2SO4, filtered and concentrated. The solvent was removed under reduced pressure and the residue was purified by column chromatography to afford the desired product (2.5g, 66%) as a brown solid. 1H NMR (300 MHz, CDCI3): 8.47 (d, J = 2.4 Hz, 1 H), 6.41 (d, J = 2.4 Hz, 1 H), 4.89 (br s, 1 H), 3.58-3.52 (m, 2H), 3.42-3.36 (m, 1 H), 3.29-3.23 (m, 1 H), 2.82 (s, 3H), 2.27-2.14 (m, 2H), 1.47 (s, 9H). –>(R)-tert-butyl methyl(1 -(6-(1 -adamantylamino)pyridazin-4-yl)pyrrolidin-3- yl)carbamate. A mixture of (R)-tert-butyl 1-(6-chloropyridazin-4-yl)pyrrolidin-3- yl(methyl) carbamate (78 mg, 0.25 mmol), 1-adamantylamine (76 mg, 0.5 mmol), BINAP (10.9 mg, 0.0175 mmol), palladium acetate(3.9 mg, 0.0175 mmol) and t-BuONa (72.1 mg, 0.75 mmol) in 1 ,2-dimethoxyethane(2 ml_) was charged with N2 The reaction mixture was stirred at 80 0C for 1.5 hours. The solution was diluted with ethyl acetate (5 ml_) and washed with 5% NaHCtheta3 solution. The solvent was removed under reduced pressure and the residue was purified by column chromatography 0-3.5% NH3 MeOH/DCM to afford the desired product (64 mg, 60%) as a colorless solid. LC-MS: m/z = 428.3 [M+H]+. (f?)-5-(3-(methylamino)pyrrolidin-1-yl)-N-(1-adamantyl)pyhdazin-3-amine dihydrochloride. (R)-tert-butyl methyl(1 -(6-(1 -adamantylamino)pyridazin-4- yl)pyrrolidin-3-yl)carbamate (120 mg, 0.28 mmol) was dissolved in MeOH (4 ml_) and 7N HCI/Et2O solution (20 ml_) was added. The resulting solution was stirred at ambient temperature for 18 hrs. The solvent was concentrated to give the desired product as a light yellow solid (73 mg, 60%). MS (ESI): mass calcd. for Ci9H29N5, 327.48 m/z found, 328.3 [M+H]+. 1H NMR (300 MHz, CD3OD): 8.15 (s, 1 H), 6.12 (s, 1 H), 4.08-3.60 (m, 5H), 2.84 (s, 3H), 2.61-2.56 (m, 1 H), 2.42-2.38 (m, 1 H), 2.20 (s, 3H), 2.10 (s, 6H), 1.87-1.77 (m, 6H)., 1837-55-4

1837-55-4 3,5-Dichloropyridazine 19959687, apyridazine compound, is more and more widely used in various fields.

Reference£º
Patent; JANSSEN PHARMACEUTICA NV; WO2009/152325; (2009); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem