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Chemical Structure| 112581-77-8 Chemical Structure| 112581-77-8

Structure of 112581-77-8

Chemical Structure| 112581-77-8

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Product Details of [ 112581-77-8 ]

CAS No. :112581-77-8
Formula : C6H3Cl2N3
M.W : 188.01
SMILES Code : ClC1=C[N]2C(=N1)C=CC(=N2)Cl
MDL No. :MFCD11044765
InChI Key :MGNCSIAIZSTMHX-UHFFFAOYSA-N
Pubchem ID :14422358

Safety of [ 112581-77-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Application In Synthesis of [ 112581-77-8 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 112581-77-8 ]

[ 112581-77-8 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 112581-77-8 ]
  • [ 927-77-5 ]
  • [ 570416-05-6 ]
YieldReaction ConditionsOperation in experiment
99% 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); In tetrahydrofuran; toluene; at 20 - 30℃;Product distribution / selectivity; Reference Example 2 Into a 500 mL reaction container purged with nitrogen, 20.4 g of <strong>[112581-77-8]2,6-dichloroimidazo[1,2-b]pyridazine</strong> (content: 92% by weight), 150mL of toluene and 0.27 g of 1,3-bis(diphenylphosphino)propanenickel chloride (II) (content: 94% by weight) were charged, and 50 mL of a tetrahydrofuran solution of n-propylmagnesium bromide (concentration: 2 mole/L) was added dropwise thereto at 20 to 30C to effect reaction. After completion of the reaction, the reaction mixture was added dropwise into 75 g of 10% by weight aqueous sulfuric acid solution. The resultant mixture was stirred and left, and the organic layer was separated. The organic layer was washed with 10% by weight aqueous sulfuric acid solution, 5% by weight aqueous sodium carbonate solution and water followed by concentrating to obtain 20.7 g of 6-n-propyl-2-chloroimidazo[1,2-b]pyridazine (purity: 94.0%). Yield: 99%
94% 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); In tetrahydrofuran; toluene; xylene; at 20 - 30℃; for 2h;Product distribution / selectivity; Reference Example 1 Into a 500 mL four-necked separable flask purged with nitrogen, 20.17 g of <strong>[112581-77-8]2,6-dichloroimidazo[1,2-b]pyridazine</strong> (content: 99.2% by weight) and 190.5 g of xylene were charged to prepare a xylene solution containing <strong>[112581-77-8]2,6-dichloroimidazo[1,2-b]pyridazine</strong>. The solution obtained by mixing 4 mL of xylene and 0.22 g of 1,3-bis(diphenylphosphino)propane and 0.62 g of a toluene solution of nickel naphthenate (II) (content: 5% by weight) were mixed to prepare a solution containing a nickel catalyst. The xylene solution containing <strong>[112581-77-8]2,6-dichloroimidazo[1,2-b]pyridazine</strong> and the solution containing a nickel catalyst were mixed, and to the resultant mixture, 63.4 g of a tetrahydrofuran solution of n-propylmagnesium bromide (content: 22.2% by weight) was added dropwise over about 2 hours at an inner temperature of 20 to 30C to effect reaction. After completion of the reaction, the reaction mixture was added dropwise into a mixture of 40.4 g of 3% by weight aqueous sulfuric acid solution and 1 g of Radiolite (which was manufactured by Showa Chemical Industry Co., LTD.). After that, the resultant mixture was stirred and filtrated. The organic layer was separated from the filtrate obtained and washed twice with about 40 g of water. The organic layer after washing was concentrated to obtain 20.9 g of 6-n-propyl-2-chloroimidazo[1,2-b]pyridazine (purity: 93.2%). Yield: 94%
88.5% 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); In tetrahydrofuran; at 0 - 20℃; for 3.16667h; <strong>[112581-77-8]2,6-Dichloroimidazo[1,2-b]pyridazine</strong> (10.0 g, 53.2 mmol) and [1,3-bis(diphenylphosphino)propane]nickel (II) dichloride (0.43 g, 0.80 mmol) were added to tetrahydrofuran (80.0 ml) under a nitrogen stream, and a solution of n-propylmagnesium bromide in tetrahydrofuran (2 M, 31.9 ml, 63.8 mmol) was added dropwise over 60 minutes to the mixture under ice-cooling. The mixture was stirred for 10 minutes under ice-cooling, and the reaction mixture was warmed to room temperature and stirred for 2 hours at room temperature. Cold water (700 ml) was added to the reaction mixture which was then acidified with conc. hydrochloric acid, and the precipitated solids were collected by filtration, and the insoluble solids were washed with dilute hydrochloric acid and then with water. On one hand, the filtrate was extracted with ethyl acetate, and the extracts were combined and washed with dilute hydrochloric acid, a saturated saline solution, an aqueous saturated sodium bicarbonate solution and a saturated saline solution in this order. The resulting organic layer was dried over anhydrous magnesium sulfate, filtrated and concentrated. The concentrated residues and the solids collected by filtration were purified by silica gel column chromatography (ethyl acetate : hexane = 3 : 7), to give the title compound as white crystals. The yield was 9.21 g (88.5%). mp 73.9-80.0C1H NMR (CDCl3, delta): 1.01(3H, t, J=7.4 Hz), 1.78(2H, m), 2.79(2H, t, J=7.6 Hz), 6.96 (1H, d, J=9.3 Hz), 7.75(1H, d, J=9.3 Hz), 7.80(1H, s). IR(Nujol, cm-1): 3122, 1466, 1377, 1314, 1302.
  • 2
  • [ 112581-77-8 ]
  • [ 42930-39-2 ]
  • [ 570416-07-8 ]
YieldReaction ConditionsOperation in experiment
96.8% 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); In tetrahydrofuran; at 0 - 20℃; for 3.75h; Zinc chloride (2.04 g, 15.0 mmol) was dried at 180C for 2 hours under vacuum and then cooled to room temperature, and anhydrous tetrahydrofuran (20.0 mL) was added thereto. n-Butyl lithium (1.6 M, 9.0 mL, 14.4 mmol) was added dropwise thereto over about 30 minutes under ice-cooling and stirred for 30 minutes under ice-cooling, to prepare a solution of n-butylzinc chloride in tetrahydrofuran. Separately, a suspension of <strong>[112581-77-8]2,6-dichloroimidazo[1,2-b]pyridazine</strong> (1.88 g, 10.0 mmol) and [1,3-bis(diphenylphosphino)propane]nickel (II) dichloride (0.16 g, 0.30 mmol) in anhydrous tetrahydrofuran (20.0 mL) was prepared under a nitrogen atmosphere, and the previously prepared solution of n-butylzinc chloride in tetrahydrofuran while being maintained at 3 to 6C was added dropwise thereto over 30 minutes. The mixture was stirred for 15 minutes under ice-cooling and for 3 hours at room temperature, then poured into a saturated saline solution and adjusted to pH 2 with dilute hydrochloric acid. The reaction solution was extracted twice with ethyl acetate, and the extracts were combined, dehydrated over anhydrous magnesium sulfate and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (ethyl acetate : hexane = 1 : 4), to give the title compound as pale yellow crystals. The yield was 2.03 g (96.8%). mp 61.0-63.0C1H NMR (CDCl3, delta): 0.96(3H, t, J=7.3 Hz), 1.41(2H, tq, J=7.5, 7.3 Hz),1.73(2H, tt, J=7.8, 7.5 Hz), 2.81(2H, t, J=7.8 Hz), 6.96(1H, d, J=9.4 Hz), 7.74(1H, d, J=9.4 Hz), 7.79(1H, s). IR(Nujol, cm-1): 3115, 3061, 1545, 1466, 1378, 1326, 1276, 817.
  • 3
  • [ 112581-77-8 ]
  • [ 2234-82-4 ]
  • [ 570416-05-6 ]
YieldReaction ConditionsOperation in experiment
48.2% 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); In tetrahydrofuran; at 10 - 60℃; for 4h; <strong>[112581-77-8]2,6-Dichloroimidazo[1,2-b]pyridazine</strong> (1.6 g, 8.5 mmol), [1,3-bis(diphenylphosphino)propane]nickel (II) dichloride (catalytic amount) and dehydrated tetrahydrofuran (20 ml) were introduced into a 100-ml three-necked flask under a nitrogen stream and stirred under ice-cooling, and a solution of propylmagnesium chloride in tetrahydrofuran (2 M, 6.4 ml, 12.8 mmol) was added dropwise thereto at 10C or less. After dropping, the mixture was stirred for 1 hour at the same temperature, for 1 hour at room temperature and for 2 hours at 50 to 60C. After the reaction was completed, the reaction solution was left and cooled, and water (50 ml) was added thereto, and the mixture was stirred and extracted with ethyl acetate (20 ml×2). The organic layers were combined, washed with water, dried over magnesium sulfate and concentrated, and the residues were purified by silica gel column chromatography (hexane : ethyl acetate = 2 : 1) to give the title compound as orange crystals (containing a small amount of impurities). The yield was 0.8 g (48.2%). mp: not measured.1H NMR (CDCl3, delta): 1.01 (3H,t,J=7.3 Hz), 1.7-1.9 (2H,m), 2.79 (2H,t,J=7.6 Hz), 6.96 (1H,d,J=9.3 Hz), 7.75 (1H,d,J=9.3 Hz), 8.19 (1H,d,J=9.4 Hz)
  • 4
  • sodium methoxide-methanol [ No CAS ]
  • [ 112581-77-8 ]
  • 2N-potassium hydrogensulfide [ No CAS ]
  • [ 35578-28-0 ]
  • 2-chloro-6-[(3-sulfamoylpropyl)thio]imidazo[1,2-b]pyridazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
In methanol; water; EXAMPLE 44 Production of 2-chloro-6-[(3-sulfamoylpropyl)thio]imidazo[1,2-b]pyridazine To a solution of 1.57 g of 3-chloro-1-propanesulfonamide in 20 ml of methanol was added 20 ml of 2N-potassium hydrogensulfide, followed by heating at 70 C. for 50 minutes. Further, 1.48 g of 28% sodium methoxide-methanol solution and 1.32 g of <strong>[112581-77-8]2,6-dichloroimidazo[1,2-b]pyridazine</strong> [Japanese Unexamined Patent Publication No. SHO 64(1989)-38092] were added to the reaction mixture, and refluxed at 100 C. for 3 hours. The mixture was concentrated under reduced pressure. Then, the residue to which was 20 ml of water was added was adjusted to pH 7.0 with 1N-hydrochloric acid. The precipitated crystals were collected by filtration and subjected to a silica gel column chromatography, eluding with chloroform and methanol (50:1). The corresponding combined fractions were concentrated, and the residue was recrystallized to obtain 1.1 g of the title compound. mp: 117-118 C. Elementary analysis: C9 H11 N4 O2 S2 Cl: Calculated (%): C, 35.23; H, 3.61; Nm 18.26. Found (%): C, 35.39; H, 3.71; N, 18.25.
  • 5
  • [ 127566-18-1 ]
  • [ 112581-77-8 ]
YieldReaction ConditionsOperation in experiment
99% With pyridine; trichlorophosphate; In chlorobenzene; at 20 - 120℃; for 6.38333h;Product distribution / selectivity; Example 4 1.88 g of 3-imino-6-chloro-2,3-dihydropyridazine-2-acetic acid (content: 99.5% by weight) was mixed with 7.52g of monochlorobenzene and 0.79 g of pyridine. To the mixture obtained, 3.84 g of phosphorus oxychloride was added dropwise over 3 minutes at an inner temperature of 20 to 40C followed by heating to an inner temperature of 120C over 20 minutes. After reacting at the same temperature for 6 hours, the mixture was cooled to obtain the reaction mixture containing 2,6-dichloro[1,2-b]pyridazine. The yield of 2,6-dichloro[1,2-b]pyridazine was 99%.
96% Example 1 41.5 g of 3-imino-6-chloro-2,3-dihydropyridazine-2-acetic acid (content: 96. 5% by weight) was mixed with 260 g of mixed xylene. To the mixture obtained, 98.1 g of phosphorus oxychloride was added at an inner temperature of 20 to 25C over 1 hour. To the mixture obtained, 32.4 g of triethylamine was added at an inner temperature of 10 to 40C over 2 hours followed by heating to an inner temperature of 120C over 3 hours. After reacting at the same temperature for 12 hours, the mixture was cooled to an inner temperature of 80C. The reaction mixture obtained was added dropwise over 1 hour into 184.8 g of water adjusted at an inner temperature of 85C. To this, 120 g of mixed xylene was added and 48% by weight aqueous sodium hydroxide solution was added to adjust pH of an aqueous layer to 4.5. An organic layer was obtained by separation procedure, and the organic layer was washed with 83 g of 1% by weight aqueous sodium hydroxide solution and then with 83 g of water. The organic layer after washing was concentrated to obtain 39.6 g of 2,6-dichloro[1,2-b]pyridazine (content: 97.0% by weight). The yield of 2,6-dichloro[1,2-b]pyridazine was 96%.
95% With 5-ethyl-2-methyl-pyridine; trichlorophosphate; at 20 - 120℃; for 6.38333h;Product distribution / selectivity; Example 2 1.88 g of 3-imino-6-chloro-2,3-dihydropyridazine-2-acetic acid (content: 99.5% by weight) was mixed with 3.64g of 2-methyl-5-ethylpyridine. To the mixture obtained, 9.22 g of phosphorus oxychloride was added dropwise over 3 minutes at an inner temperature of 20 to 40C followed by heating to an inner temperature of 120C over 20 minutes. After reacting at the same temperature for 6 hours, the mixture was cooled to obtain the reaction mixture containing 2,6-dichloro[1,2-b]pyridazine. The yield of 2,6-dichloro[1,2-b]pyridazine was 95%.
90% With N,N-dimethylaniline hydrochloride; trichlorophosphate; at 20 - 120℃; for 6.38333h;Product distribution / selectivity; Examples 3 According to the same manner as that described in Example 2, the reaction mixture containing 2,6-dichloroimidazo[1,2-b]pyridazine was obtained except that 4.70 g of dimethylaniline hydrochloride salt was used in place of 3.64 g of 2-methyl-5-ethylpyridine. The yield of 2,6-dichloro[1,2-b]pyridazine was 90%.
73% With N-ethyl-N,N-diisopropylamine; trichlorophosphate; In xylene; at 10 - 120℃; for 15h;Product distribution / selectivity; Example 7; To the mixture prepared by mixing 10.0 g of 3-imino-6-chloro-2,3-dihydropyridazine-2-acetic acid (content: 98% by weight) with 62.7 g of xylene, 24.0 g of phosphorus oxychloride was added dropwise at an inner temperature of 10 to 30C followed by adding dropwise 10.13 g of diisopropylethylamine at an inner temperature of 10 to 50C. The mixture obtained was heated to 120C. After reacting at the same temperature for 15 hours, the mixture was cooled to obtain the reaction mixture containing 2,6-dichloro[1,2-b]pyridazine. The yield of 2,6-dichloro[1,2-b]pyridazine was 73%.
61 - 62% With triethylamine; trichlorophosphate; In xylene; at 10 - 120℃; for 21 - 24h;Product distribution / selectivity; Example 5 To the mixture prepared by mixing 10.0 g of 3-imino-6-chloro-2,3-dihydropyridazine-2-acetic acid (content: 98% by weight) with 62.7 g of xylene, 24.0 g of phosphorus oxychloride was added dropwise at an inner temperature of 10 to 30C followed by adding dropwise 15.8 g of triethylamine at an inner temperature of 10 to 50C. The mixture obtained was heated to 120C. After reacting at the same temperature for 21 hours, the mixture was cooled to obtain the reaction mixture containing 2,6-dichloro[1,2-b]pyridazine. The yield of 2,6-dichloro[1,2-b]pyridazine was 61%. Example 6; To the mixture prepared by mixing 10.0 g of 3-imino-6-chloro-2,3-dihydropyridazine-2-acetic acid (content: 98% by weight) with 62.7 g of xylene, 12.0 g of phosphorus oxychloride was added dropwise at an inner temperature of 10 to 30C followed by adding dropwise 2.64 g of triethylamine at an inner temperature of 10 to 50C. The mixture obtained was heated to 120C. After reacting at the same temperature for 24 hours, the mixture was cooled to obtain the reaction mixture containing 2,6-dichloro[1,2-b]pyridazine. The yield of 2,6-dichloro[1,2-b]pyridazine was 62%.
22% With trichlorophosphate; at 20 - 120℃; for 6.38333h;Product distribution / selectivity; Comparative Example 1 To 1.88 g of 3-imino-6-chloro-2,3-dihydropyridazine-2-acetic acid (content: 99.5% by weight), 9.22 g of phosphorus oxychloride was added dropwise over 3 minutes at an inner temperature of 20 to 40C. The mixture obtained was heated to an inner temperature of 120C over 30 minutes. After reacting at the same temperature for 6 hours, the mixture was cooled to obtain the reaction mixture containing 2,6-dichloro[1,2-b]pyridazine. The yield of 2,6-dichloro[1,2-b]pyridazine was 22%.
0.4% Comparative Example 2 1.88 g of 3-imino-6-chloro-2,3-dihydropyridazine-2-acetic acid (content: 99.5% by weight) was mixed with 7.29g of 2-methyl-5-ethylpyridine. To the mixture obtained, 4.61 g of phosphorus oxychloride was added dropwise while keeping an inner temperature of 40C or less followed by heating to an inner temperature of 120C. After reacting at the same temperature for 6 hours, the mixture was cooled to obtain the reaction mixture containing.2,6-dichloro[1,2-b]pyridazine. The yield of 2,6-dichloro[1,2-b]pyridazine was 0.4%.

  • 6
  • [ 5469-69-2 ]
  • [ 79-11-8 ]
  • [ 112581-77-8 ]
YieldReaction ConditionsOperation in experiment
20% To a mixture of 6-chloropyridazin-3 -amine (1 g, 7.7 mmol), ethanol (10 ml) and water (10 ml) were added triethylamine (781 mg, 1.08 ml, 7.7 mmol) and 2-chloroacetic acid (729 mg, 7.7 mmol) at r.t under an argon atmosphere. The mixture was heated at 80 for 24 firs. The reaction mixture was evaporated to dryness. The resulting solid was mixed with phosphoryl trichloride (20.8 g, 12.7 ml, 136 mmol) and the mixture was heated at 120 under an argon atmosphere overnight. Phosphoryl trichloride was evaporated. The residue was quenched with ice/water. The pH was adjusted to 10 with NaOH 4 N and the product was extracted with EtOAc, dried over MgS04, filtered and evaporated. The crude product was purified by silica gel chromatography using a n-heptane/EtOAc gradient as eluent, to obtain the title compound (296 mg, 20%) as light yellow solid. MS: M = 188.1 (M+H)+
 

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