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Chemical Structure| 212779-33-4 Chemical Structure| 212779-33-4

Structure of 212779-33-4

Chemical Structure| 212779-33-4

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Product Details of [ 212779-33-4 ]

CAS No. :212779-33-4
Formula : C10H6Cl3N3
M.W : 274.53
SMILES Code : NC1=NC(Cl)=CN=C1C2=CC=CC(Cl)=C2Cl
MDL No. :MFCD28978779
InChI Key :UAZFZHXRKHSGLQ-UHFFFAOYSA-N
Pubchem ID :18180212

Safety of [ 212779-33-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319
Precautionary Statements:P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313

Application In Synthesis of [ 212779-33-4 ]

* 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 [ 212779-33-4 ]

[ 212779-33-4 ] Synthesis Path-Downstream   1~2

  • 1
  • 2-amino-3-bromo-6-chloropyrazine [ No CAS ]
  • [ 151169-74-3 ]
  • [ 212779-33-4 ]
YieldReaction ConditionsOperation in experiment
91% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; water; at 120℃;Inert atmosphere; Compound B1-1 (5.00g, 24.0mmol, 1.0eq.),2,3-Dichlorophenylboronic acid (5.04g, 26.4mmol, 1.1eq.), Pd(dppf)Cl2 (350.1mg, 2mol%) and K3PO4(10.18g, 48.0mmol, 2.0eq.) was placed in a 200mL single-neck flask, and the system was evacuated to replace nitrogen.Add 1,4-dioxane (54 mL) and water (6 mL) to react overnight in an oil bath at 120C, and monitor until the conversion of the raw materials is complete. Diatomite filtration,The filtrate was concentrated, and 30mL ethyl acetate was added for extraction,Wash with saturated sodium chloride aqueous solution 3 times, concentrate, and purify by column chromatography.Compound B1-2 (5.94 g, yield 91%) was obtained.
80% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; water; at 70℃; for 12h;Inert atmosphere; The mixture of 3-bromo-6-chloropyrazin-2-amine (600 mg, 2.87 mmol, 1.0 eq, CAS 212779-21-0), (2,3-dichlorophenyl)boronic acid (547 mg, 2.87 mmol, 1.0 eq), Pd(dppf)Cl2 (210 mg, 287 pmol, 0.1 eq) and K3PO4 (1.82 g, 8.61 mmol, 3.0 eq) in dioxane (15 mL) and H20 (3 mL) was evacuated and refilled 3 times with N2 gas, then stirred at 70 C for 12 hours. The mixture was concentrated under reduced pressure to afford a residue, which was purified by column chromatography (petroleum ether / ethyl acetate = 1 : 0 ~ 10 : 1) to afford 6-chloro-3-(2,3-dichlorophenyl)pyrazin-2-amine (630 mg, 80% yield) as a yellow solid. LCMS m/z [M+H]+ = 273.9/275.9.
74% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In tetrahydrofuran; water; for 4h;Inert atmosphere; Reflux; General procedure: To a clean dry round-bottom flask, which was purged with nitrogen to remove water traces and other particles, 3-bromo-6-chloropyrazin-2-amine (1.0 eq) was added and dissolved in dry THF (10 volumes). Then, (2,3-dichlorophenyl) boronic acid (1.3 to 1.5 eq) was added and stirred for 10 min under inert atmosphere. The reaction mass was degassed using a nitrogen inlet and vacuum outlet for 15 min. Tetrakis (triphenylphosphine) palladium (0) (0.1 eq) was added and stirred for 15 min. After the addition of a solution of 2 M Na2CO3, the reaction mixture was slowly heated to reflux. The process of the reaction was evaluated by TLC and LCMS. After the solution was stirred for 4 h, it was cooled to RT. Ethyl acetate and water were added, and the reaction mixture was stirred for another10 min. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine and dried over sodium sulfate. After evaporation of the solvent, the crude product was purified by ash chromatography (0% to 50% gradient of ethyl acetate/n-hexane) to get 6-chloro-3-(2,3-dichlorophenyl)pyrazin-2-amine (3) as a yellow crystalline solid. MS m/z 274.10/276.11 (M + H)+.
70% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 110℃; for 6h;Inert atmosphere; [00693] 3-Bromo-6-chloropyrazine-2-amine (5.00 g, 24.0 mmol) and Na2C03 10H2O (20.6 g, 72.0 mmol) were suspended in mixture dioxane: water, 4: 1. The solvent was degassed by passing argon through it and Pd(dppf)Ch (0.88 g, 1.20 mmol) was added. The reaction was carried out 6 hrs at 110 C. The reaction mixture was filtered through celite pad (AcOEt). The residue was purified by column chromatography (hexane: AcOEt, 9: 1 -> 4: 1) to give 4.63 g (70%) of 6-chloro-3-(2,3-dichlorophenyl)pyrazin-2-amine . NMR (400 MHz, DMSO- d6) δ 7.85 (s, 1H), 7.74 (dd, J = 8.0, 1.6 Hz, 1H), 7.47 (t, J = 7.8 Hz, 1H), 7.39 (dd, J = 7.6, 1.6 Hz, 1H), 6.70 (s, 2H). LC-MS (ESI) m/z: [M + H] found 275.7.
63% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; water; at 80℃; for 16h; To a solution of 3-bromo-6-chloropyrazin-2-amine (30 g, 144 mmol, 1 equiv) in dioxane (360 mL) was added (2,3-dichlorophenyl)boronic acid (33 g, 173 mmol, 1.2 equiv), a solution of K3PO4 (92 g, 432 mmol, 3.0 equiv) in H20 (36 mL), and Pd(dppf)Cl2 (11 g, 14.4 mmol, 0.1 equiv). The reaction mixture was warmed to 80 C and stirred for 16 hours, after which the solution was concentrated under reduced pressure. The residue was purified by silica gel chromatography to give 6-chloro-3-(2,3-dichlorophenyl)pyrazin-2-amine (25 g, 91 mmol, 63% yield) as a yellow solid. 1H MR (400 MHz, DMSO-d6) δ 7.87 - 7.82 (m, 1 H), 7.73 (dd, J = 7.94, 1.54 Hz, 1H), 7.50 - 7.44 (m, 1H), 7.41 - 7.36 (m, 1H), 6.69 (br s, 2 H).
47% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 2h;Inert atmosphere; A 500 mL single-necked eggplant flask was charged with 3-bromo-6-chloropyrazin-2-amine (14.0 g, 67.3 mmol, 1 eq) and2,3-Dichlorobenzeneboronic acid (19.3 g, 101 mmol, 1.5 eq),Then add 188mL of dioxane and47mL water mixed solvent,Cesium carbonate (54.8 g, 168 mmol, 2.5 eq) was addedPd (dppf) Cl2 (5.5 g, 6.7 mmol, 0.1 eq),Under nitrogen protection,Then warmed to 90 reaction 2h, poured into water,The mixture was extracted with ethyl acetate. The crude product was purified by column chromatography using ethyl acetate / petroleum ether (1/10) as developing solvent. The developing solvent was spin-dried and dried in vacuo to give 8.7 g of a green solid,Chloro-3- (2,3-dichlorophenyl) pyrazin-2-amine (47% yield, HPLC purity 98%).
38% With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; acetonitrile; at 130℃; for 18h;Inert atmosphere; To a stirred solution of 3-bromo-6-chloropyrazin-2-amine (2 g, 9.61 mmol) in ACN: H2O (20 ml, 9:1), (2,3-dichlorophenyl)boronic acid (2, 2.7 g, 14.2 mmol), potassium phosphate tribasic (6.10 g, 28.8 mmol) were added. The reaction mixture was degassed with argon for a 10 min and Pd(dppf)Cl2CH2Cl2(0.78 g, 0.96 mmol) was added. The reaction mixture was degassed again with argon and heated at 130 C. with stirring for 18 h. Progress of the reaction was monitored by TLC, which showed complete consumption of starting material. The reaction mixture was allowed to cool to room temperature and concentrated. The residue was diluted with water (100 mL) and the extracted with EtOAc (3*200 mL). The combined organic layer was washed with brine (300 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography [silica gel (100-200 mesh), gradient 10-12% ethyl acetate in hexane] to give 6-chloro-3-(2,3-dichlorophenyl)pyrazin-2-amine (1.0 g, 38%) as a yellow solid. MS (ESI+ve): 274.12 1H-NMR (400 MHz; CDCl3): δ 8.02 (s, 1H), 7.58-7.60 (d, J=8.02 Hz, 1H), 7.32-7.36 (m, 2H), 4.63 (bs, 2H).
633 mg With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; acetonitrile; at 120℃; for 4h;Microwave irradiation; Intermediate 6 6-(4-amino-4-methylpiperidin-l-yl)-3-(2.3-dichlorophenyl)pyrazin-2-amine [00240] A suspension of 3-bromo-6-chloropyrazin-2-amine (1.2 g, 5.76 mmol), (2,3- dichlophenyl)boronic acid (1.1 g, 5.76 mmol), potassium phosphate (3.67 g, 17.27 mmol), and PdCl2(dppf) DCM adduct (235 mg, 0.288 mmol) in MeCN:H20 (9: 1, 15 mL, degassed) was stirred in a microwave reactor for 4 h at 120 C. After cooling to RT, the reaction was filtered through a pad of Celite followed by EtOAc (25 mL) wash. The combined filtrates were concentrated and the resulting residue was purified by silica chromatography (0 to 30% gradient of EtO Ac/heptane) to give 6-(4-amino-4-methylpiperidin-l-yl)-3-(2,3-dichlorophenyl)pyrazin-2- amine (633 mg, 2.306 mmol). MS m/z 276.4 (M+H)+.
633 mg With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In water; acetonitrile; at 120℃; for 4h;Microwave irradiation; A suspension of 3-bromo-6-chloropyrazin-2-amine (1.2 g, 5.76 mmol), (2,3- dichlophenyl)boronic acid (1.1 g, 5.76 mmol), potassium phosphate (3.67 g, 17.27 mmol), and PdCl2(dppf) DCM adduct (235 mg, 0.288 mmol) in MeCN:H20 (9: 1, 15 mL, degassed) was stirred in a microwave reactor for 4 h at 120 C. After cooling to RT, the reaction was filtered through a pad of Celite followed by EtO Ac (25 mL) wash. The combined filtrates were concentrated and the resulting residue was purified by silica chromatography (0 to 30% gradient of EtO Ac/heptane) to give 6-(4-amino-4-methylpiperidin-l-yl)-3-(2,3-dichlorophenyl)pyrazin-2- amine (633 mg, 2.306 mmol). MS m/z 276.4 (M+H)+.
633 mg With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; acetonitrile; at 120℃; for 4h;Microwave irradiation; A suspension of 3-bromo-6-chloropyrazin-2-amine (1.2 g, 5.76 mmol), (2,3-dichlophenyl)boronic acid (1.1 g, 5.76 mmol), potassium phosphate (3.67 g, 17.27 mmol), and PdCl2(dppf).DCM adduct (235 mg, 0.288 mmol) in MeCN:H20 (9:1, 15 mE, degassed) was stirred in a microwave reactor for 4 h at 120 C. After cooling to RT, the reaction was filtered through a pad of Celite followed by EtOAc (25 mE) wash. The combined filtrates were concentrated and the resulting residue was purified by silica chromatography (0 to 30% gradient of EtOAc/heptane) to give 6-(4-amino-4- methylpiperidin-1 -yl)-3-(2,3-dichlorophenyl)pyrazin-2-amine (633 mg, 2.306 mmol). MS mlz 276.4 (M+H).
633 mg With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; acetonitrile; at 120℃; for 4h;Microwave irradiation; 6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazin-2-amine A suspension of 3-bromo-6-chloropyrazin-2-amine (1.2 g, 5.76 mmol), (2,3-dichlophenyl)boronic acid (1.1 g, 5.76 mmol), potassium phosphate (3.67 g, 17.27 mmol), and PdCl2(dppf).DCM adduct (235 mg, 0.288 mmol) in MeCN:H2O (9:1, 15 mL, degassed) was stirred in a microwave reactor for 4 h at 120 C. After cooling to RT, the reaction was filtered through a pad of Celite followed by EtOAc (25 mL) wash. The combined filtrates were concentrated and the resulting residue was purified by silica chromatography (0 to 30% gradient of EtOAc/heptane) to give 6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazin-2-amine (633 mg, 2.306 mmol). MS m/z 276.4 (M+H)+.

  • 2
  • [ 205672-25-9 ]
  • [ 151169-74-3 ]
  • [ 212779-33-4 ]
YieldReaction ConditionsOperation in experiment
48.6% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In water; acetonitrile; at 100℃; for 6h; A suspension of 3-bromo-6-chloropyrazin-2-amine 1 (5g, 24mmol), (2,3-dichlophenyl)boronic acid 6 (5.5g, 28.8mmol), potassium carbonate (9.95g, 72mmol), and PdCl2(dppf) DCM adduct (1.175g, 1.44mmol) in MeCN:H20 (5:1, 90mL, degassed) was stirred for 6h at 100C and then cooled to room temperature, the reaction was filtered and filtrates were concentrated under reduced pressure, the resulting residue was purified by flash column chromatography (petroleum ether: ethyl acetate=5:1) to give 6-chloro-3-(2,3-dichlorophenyl)pyrazin-2-amine 7 as a yellow compound (3.2g, 11.66mmol, 48.6% yield). 1H NMR (400MHz, CDCl3) δ 7.41 (dd, J=8.0, 1.7Hz, 1H), 7.31 (s, 1H), 7.29 (s, 1H), 7.22 (dd, J=8.2, 1.7Hz, 1H), 5.21 (s, 2H).
48.6% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In water; acetonitrile; at 100℃; for 6h; A suspension of 3-bromo-6-chloropyrazin-2-amine 1 (5g, 24mmol), (2,3-dichlophenyl)boronic acid 6 (5.5g, 28.8mmol), potassium carbonate (9.95g, 72mmol), and PdCl2(dppf) DCM adduct (1.175g, 1.44mmol) in MeCN:H20 (5:1, 90mL, degassed) was stirred for 6h at 100C and then cooled to room temperature, the reaction was filtered and filtrates were concentrated under reduced pressure, the resulting residue was purified by flash column chromatography (petroleum ether: ethyl acetate=5:1) to give 6-chloro-3-(2,3-dichlorophenyl)pyrazin-2-amine 7 as a yellow compound (3.2g, 11.66mmol, 48.6% yield). 1H NMR (400MHz, CDCl3) δ 7.41 (dd, J=8.0, 1.7Hz, 1H), 7.31 (s, 1H), 7.29 (s, 1H), 7.22 (dd, J=8.2, 1.7Hz, 1H), 5.21 (s, 2H).
 

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