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Chemical Structure| 867165-51-3 Chemical Structure| 867165-51-3

Structure of 867165-51-3

Chemical Structure| 867165-51-3

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Product Details of [ 867165-51-3 ]

CAS No. :867165-51-3
Formula : C11H12ClN3O
M.W : 237.69
SMILES Code : O=C(C1CC(C1)=C)NCC2=NC=CN=C2Cl
MDL No. :MFCD30470742

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Application In Synthesis of [ 867165-51-3 ]

* 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 [ 867165-51-3 ]

[ 867165-51-3 ] Synthesis Path-Downstream   1~2

  • 1
  • (3-chloropyrazin-2-yl)methylamine bis-hydrochloride [ No CAS ]
  • [ 15760-36-8 ]
  • [ 867165-51-3 ]
YieldReaction ConditionsOperation in experiment
With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃;Product distribution / selectivity; C-(3-Chloropyrazin-2-yl)-methylamine bis-HCl (1.0 g, 4.62 mmol), N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide (EDC) (1.31 g, 6.47 mmol, 1.4 eq.), 4-dimethylamino pyridine (DMAP) (0.141 g, 1.15 mmol, 0.25 eq.), and diisopropylethylamine (DIPEA) (2.42 mL, 1.79 g, 13.9 mmol, 3.0 eq.) were dissolved in anhydrous CH2Cl2 (25 mL). To this solution, a solution of <strong>[15760-36-8]3-methylenecyclobutanecarboxylic acid</strong> (0.622 g, 5.54 mmol, 1.2 eq.) in anhydrous CH2Cl2 (25 mL) was added under N2 and the reaction was allowed to stir overnight at rt. Reaction mixture was concentrated in vacuo and the resulting residue was dissolved in EtOAc, washed with water (2×), NaHCO3 (1×), water (1×), and brine (1×), dried over Na2SO4, filtered, and concentrated in vacuo, giving crude title compound, as a brown oil. The crude material was purified by chromatography on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with EtOAc:Hex 10%→20% -40% -70%], affording the title compound as a pale yellow solid. Additionally, the title compound could be prepared by the following route: 1,1'-Carbonyldiimidazole (CDI) (0.824 g, 5.08 mmol, 1.1 eq.) and <strong>[15760-36-8]3-methylenecyclobutanecarboxylic acid</strong> (0.570 g, 5.08 mmol, 1.1 eq.) were dissolved in anhydrous THF (12 mL) and allowed to stir at 60 C. for 2 h. A solution of C-(3-chloropyrazin-2-yl)-methylamine bis-HCl (1.0 g, 4.62 mmol) and diisopropylethylamine (DIPEA) (2.42 mL, 1.79 g, 13.9 mmol, 3.0 eq.) in anhydrous CH2Cl2 (13 mL) was added to the acid mixture and the reaction was allowed to stir at 60 C., under N2, overnight. The reaction mixture was concentrated in vacuo and the resulting residue was dissolved in EtOAc, washed with NaHCO3 (2×) and brine (1×), dried over Na2SO4, filtered, and concentrated in vacuo, giving crude title compound, as a brown oil. The crude material was purified by chromatography on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with EtOAc:Hex 10%→20%→40%→70%], affording the title compound as a pale yellow solid; 1H NMR (CDCl3, 400 MHz) δ 2.86-2.96 (m, 2H), 3.03-3.19 (m, 3H), 4.72 (dd, J=4.4, 0.8 Hz, 2H), 4.79-4.84 (m, 2H), 6.78 (s, -NH), 8.32-8.34 (m, 1H), 8.46 (d, J=2.8 Hz, 1H); MS (ES+): m/z 238.19 (90) [MH+]; HPLC: tR=2.67 min (OpenLynx, polar-7 min).
C-(3-Chloropyrazin-2-yl)-methylamine bis-HCl (1.0 g, 4.62 mmol), N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide (EDC) (1.31 g, 6.47 mmol, 1.4 eq.), 4-dimethylamino pyridine (DMAP) (0.141 g, 1.15 mmol, 0.25 eq.), and diisopropylethylamine (DIPEA) (2.42 mL, 1.79 g, 13.9 mmol, 3.0 eq.) were dissolved in anhydrous CH2Cl2 (25 mL). To this solution, a solution of <strong>[15760-36-8]3-methylenecyclobutanecarboxylic acid</strong> (0.622 g, 5.54 mmol, 1.2 eq.) in anhydrous CH2Cl2 (25 mL) was added under N2 and the reaction was allowed to stir overnight at rt. Reaction mixture was concentrated in vacuo and the resulting residue was dissolved in EtOAc, washed with water (2×), NaHCO3 (1×), water (1×), and brine (1×), dried over Na2SO4, filtered, and concentrated in vacuo, giving crude title compound, as a brown oil. The crude material was purified by chromatography on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with EtOAc:Hex 10%→20% -40% -70%], affording the title compound as a pale yellow solid. Additionally, the title compound could be prepared by the following route: 1,1'-Carbonyldiimidazole (CDI) (0.824 g, 5.08 mmol, 1.1 eq.) and <strong>[15760-36-8]3-methylenecyclobutanecarboxylic acid</strong> (0.570 g, 5.08 mmol, 1.1 eq.) were dissolved in anhydrous THF (12 mL) and allowed to stir at 60 C. for 2 h. A solution of C-(3-chloropyrazin-2-yl)-methylamine bis-HCl (1.0 g, 4.62 mmol) and diisopropylethylamine (DIPEA) (2.42 mL, 1.79 g, 13.9 mmol, 3.0 eq.) in anhydrous CH2Cl2 (13 mL) was added to the acid mixture and the reaction was allowed to stir at 60 C., under N2, overnight. The reaction mixture was concentrated in vacuo and the resulting residue was dissolved in EtOAc, washed with NaHCO3 (2×) and brine (1×), dried over Na2SO4, filtered, and concentrated in vacuo, giving crude title compound, as a brown oil. The crude material was purified by chromatography on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with EtOAc:Hex 10%→20%→40%→70%], affording the title compound as a pale yellow solid; 1H NMR (CDCl3, 400 MHz) δ 2.86-2.96 (m, 2H), 3.03-3.19 (m, 3H), 4.72 (dd, J=4.4, 0.8 Hz, 2H), 4.79-4.84 (m, 2H), 6.78 (s, -NH), 8.32-8.34 (m, 1H), 8.46 (d, J=2.8 Hz, 1H); MS (ES+): m/z 238.19 (90) [MH+]; HPLC: tR=2.67 min (OpenLynx, polar-7 min).; 1,1'-Carbonyldiimidazole (CDI) (8.24 g, 50.81 mmol) and <strong>[15760-36-8]3-methylenecyclobutanecarboxylic acid</strong> (5.70 g, 50.81 mmol) were dissolved in anhydrous THF (100 mL) and allowed to stir at 60 C. for 4 h. A solution of C-(3-Chloropyrazin-2-yl)methylamine bis-hydrochloride (10.0 g, 46.19 mmol) and diisopropylethylamine (DIPEA) (32.30 mL, 184.76 mmol) in anhydrous CH2Cl2 (150 mL) was added to the mixture and the reaction was allowed to stir at rt for 24 h. The mixture was concentrated in vacuo, the residue dissolved in EtOAc and the resulting solution washed with saturated NaHCO3 (aq.) water H2O and Brine. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to afford crude product, which was purified by chromatography over silica gel eluting with 50-70% EtOAc/hexane to yield desired product. 1H NMR (400 MHz, CDCl3) δ ppm 2.92-2.94 (2 H, m), 3.05-3.14 (2 H, m), 4.60 (2 H, d, J=4.24 Hz), 4.80-4.84 (2 H, m), 6.75 (1 H, brs), 8.33 (1 H, d, J=4.22 Hz) and 8.45 (1 H, d, J=2.54 Hz). MS (ES+): m/z 238 and 240 [MH+].
  • 2
  • (3-chloropyrazin-2-yl)methanamine bishydrochloride salt [ No CAS ]
  • [ 15760-36-8 ]
  • [ 867165-51-3 ]
YieldReaction ConditionsOperation in experiment
With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; C-(3-Chloropyrazin-2-yl)-methylamine bis-HCl (1.0 g, 4.62 mmol), N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide (EDC) (1.31 g, 6.47 mmol, 1.4 eq.), 4-dimethylamino pyridine (DMAP) (0.141 g, 1.15 mmol, 0.25 eq.), and diisopropylethylamine (DIPEA) (2.42 mL, 1.79 g, 13.9 mmol, 3.0 eq.) were dissolved in anhydrous CH2Cl2 (25 mL). To this solution, a solution of <strong>[15760-36-8]3-methylenecyclobutanecarboxylic acid</strong> (0.622 g, 5.54 mmol, 1.2 eq.) in anhydrous CH2Cl2 (25 mL) was added under N2 and the reaction was allowed to stir overnight at rt. Reaction mixture was concentrated in vacuo and the resulting residue was dissolved in EtOAc, washed with water (2×), NaHCO3 (1×), water (1×), and brine (1×), dried over Na2SO4, filtered, and concentrated in vacuo, giving crude title compound, as a brown oil. The crude material was purified by chromatography on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with EtOAc:Hex 10%→20%→40%→70%], affording the title compound as a pale yellow solid. Additionally, the title compound could be prepared by the following route: 1,1'-Carbonyldiimidazole (CDI) (0.824 g, 5.08 mmol, 1.1 eq.) and <strong>[15760-36-8]3-methylenecyclobutanecarboxylic acid</strong> (0.570 g, 5.08 mmol, 1.1 eq.) were dissolved in anhydrous THF (12 mL) and allowed to stir at 60 C. for 2 h. A solution of C-(3-chloropyrazin-2-yl)-methylamine bis-HCl (1.0 g, 4.62 mmol) and diisopropylethylamine (DIPEA) (2.42 mL, 1.79 g, 13.9 mmol, 3.0 eq.) in anhydrous CH2Cl2 (13 mL) was added to the acid mixture and the reaction was allowed to stir at 60 C., under N2, overnight. The reaction mixture was concentrated in vacuo and the resulting residue was dissolved in EtOAc, washed with NaHCO3 (2×) and brine (1×), dried over Na2SO4, filtered, and concentrated in vacuo, giving crude title compound, as a brown oil. The crude material was purified by chromatography on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with EtOAc:Hex 10%→20%→40%→70%], affording the title compound as a pale yellow solid; 1H NMR (CDCl3, 400 MHz) δ 2.86-2.96 (m, 2H), 3.03-3.19 (m, 3H), 4.72 (dd, J=4.4, 0.8 Hz, 2H), 4.79-4.84 (m, 2H), 6.78 (s, -NH), 8.32-8.34 (m, 1H), 8.46 (d, J=2.8 Hz, 1H); MS (ES+): m/z 238.19 (90) [MH+]; HPLC: tR=2.67 min (OpenLynx, polar-7 min).
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃;Inert atmosphere; 3-Methylene-cyclobutanecarboxylic acid (3-chloropyrazin-2-ylmethyl)amideC-(3-Chloropyrazin-2-yl)-methylamine bis-HCl (1.0 g, 4.62 mmol), N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide (EDC) (1.31 g, 6.47 mmol, 1.4 eq.), 4-dimethylamino pyridine (DMAP) (0.141 g, 1.15 mmol, 0.25 eq.), and DIEA (2.42 mL, 1.79 g, 13.9 mmol, 3.0 eq.) were dissolved in anhydrous CH2Cl2 (25 mL). To this solution, a solution of <strong>[15760-36-8]3-methylenecyclobutanecarboxylic acid</strong> (0.622 g, 5.54 mmol, 1.2 eq.) in anhydrous CH2Cl2 (25 mL) was added under N2 and the reaction was allowed to stir overnight at rt. Reaction mixture was concentrated in vacuo and the resulting residue was dissolved in EtOAc, washed with water (2×), NaHCO3 (1×), water (1×), and brine (1×), dried over Na2SO4, filtered, and concentrated in vacuo, giving crude title compound, as a brown oil. The crude material was purified by chromatography on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with 10% hexane in ethyl acetate, affording the title compound as a pale yellow solid.
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 0 - 20℃; for 1h; To a solution of (3-chloropyrazin-2-yl)methanamine bis hydrochloride 5-a (5.0 g, 23.1mmol) in DMF (46.2 ml) cooled to 0C were sequentially added 3- methylenecyclobutanecarboxilic acid 32-a (3.1 g, 27.7 mmol), HATU (8.8 g, 23.1 mmol), and TEA (16.1 ml, 115.0 mmol), and the reaction mixture was stirred for 1 hour at room temperature. Water and dichloromethane were added, the organic layer was separated, the aqueous phase was extracted twice with dichloromethane, the combined organic extracts were washed with a saturated aqueous solution of ammonium chloride and brine, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to provide Intermediate 32-b as a yellow solid.
 

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