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Chemical Structure| 893428-66-5 Chemical Structure| 893428-66-5

Structure of 893428-66-5

Chemical Structure| 893428-66-5

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Product Details of [ 893428-66-5 ]

CAS No. :893428-66-5
Formula : C7H6F2N2O
M.W : 172.13
SMILES Code : O=C(N)C1=C(F)C=C(F)C=C1N
MDL No. :MFCD15528762

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Application In Synthesis of [ 893428-66-5 ]

* 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 [ 893428-66-5 ]

[ 893428-66-5 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 126674-77-9 ]
  • [ 893428-66-5 ]
YieldReaction ConditionsOperation in experiment
78% With ammonia; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In tetrahydrofuran; dioxanes; N,N-dimethyl acetamide; at 20℃; for 24h; Alternate Protocol I: Synthesis of o-amino carboxamides from benzoic acids; Intermediate A11 : 2-amino-4,6-difluorobenzamide; To a solution of 2-amino-4,6-difluoro benzoic acid (4.Og, 23.12 mmol, Butt Park Ltd.) in tetrahydrofuran (1.0 L) and N,N-dimethylacetamide (150 mL) was added EDCIetaCI (13.44g, 70 mmol, Aldrich), HOBT (9.5g, 70 mmol, Aldrich) and ammonia as a 0.5M solution in dioxanes (460 mL, 230 mmol, Aldrich). The resultant slurry was stirred for 24 hours, and then solids removed by filtration through celite. The filtrate was taken to a residue under reduced pressure and partitioned between water and ethyl <n="75"/>acetate. The organic layer was dried over sodium sulfate, filtered, taken to a residue under reduced pressure, and purified by chromatography on SiO2 (Ethyl acetate/Hexanes) to afford analytically pure 2-amino-4,6-difluorobenzamide as a white crystalline solid (3.1 1g, 78% yield); 1 H NMR (400 MHz, DMSOd6) delta ppm 6.21 - 6.27 (m, 1 H), 6.27 - 6.32 (m, 1 H), 6.52 (s, 2 H), 7.48 (s, 1 H), 7.53 (s, 1 H).
50% Example 15. Preparation of 5,7-difluoro-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazoIin-4(3H)-one [0207] A mixture of 3,5-dimethoxy-4-hydroxybenzaldehyde (10 g, 66.67 mmol), (2-bromoethoxy)-dimethyl-tert-butylsilane (15 ml_, 70 mmol), potassium iodide (1.1 g, 6.67 mmol), and sodium hydride (4.00 g, 100 mmol) in DMF (150 ml_) was heated and stirred at 7O0C for 14 hours. The reaction was then cooled and quenched by addition of water (100 ml_). The mixture was extracted with EtOAc (3 * 100 ml_) and concentrated on a rotary evaporator. The resulting residue was purified by column (Sitheta2, hexanes/EtOAc = 6:1) to yield 4-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3,5-dimethyl-benzaldehyde (15.4 g, 75%). [0208] A solution of <strong>[126674-77-9]2-amino-4,6-difluorobenzoic acid</strong> (0.5 g, 2.9 mmol), EDCI HCI (0.887 g, 4.62 mmol), HOBt (0.975 g, 7.22 mmol), and triethylamine (1.6 ml_, 11.552 mmol) in THF (50 ml_) was stirred at room temperature for 1 hour. Ammonium hydroxide (50% aqueous, 10 ml_) was then added to the reaction mixture. The resulting mixture was stirred at room temperature for 6 hours. The reaction was quenched by adding water (50 ml_), extracted with DCM (3 * 100 mL), and concentrated on a rotary evaporator to afford 2-amino-4,6-difluorobenzamide (0.25 g, 50%).[0209] A mixture of 2-amino-4,6-difluoro benzamide (0.25 g, 1.45 mmol), 4- [2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3,5-dimethyl-benzaldehyde (0.448 g, 1.45 mmol), sodium hydrogensulfite (0.26 g, 1.45 mmol) and p-toluenesulfonic acid (0.276 g, 1.45 mmol) in N,N-dimethyl acetamide (10 mL) was stirred at 155C for 14 hours. The reaction mixture was cooled to room temperature, diluted with water (50 mL), extracted with EtOAc (3 * 100 mL), and concentrated on a rotary evaporator, to afford impure product. The residue was re-dissolved in THF (20 mL) and mixed with TBAF in THF (10 mL, 10 mmol). The reaction mixture was stirred at room temperature for 3 hours and concentrated on a rotary evaporator to afford an oily residue. Further purification by column (Sitheta2, EtOAc/DCM = 3:1) yielded a light yellow solid. This solid was diluted with MeOH (10 ml_) to make a slurry. The solid was collected by filtration and washed with MeOH to afford the title compound as a light yellow solid (49 mg, 5% overall yield).
50% A solution of <strong>[126674-77-9]2-amino-4,6-difluorobenzoic acid</strong> (0.5 g, 2.9 mmol), EDCl HCl (0.887 g, 4.62 mmol), HOBt (0.975 g, 7.22 mmol), and triethylamine (1.6 mL, 11.552 mmol) in THF (50 mL) was stirred at room temperature for 1 hour. Ammonium hydroxide (50% aqueous, 10 mL) was then added to the reaction mixture. The resulting mixture was stirred at room temperature for 6 hours. The reaction was quenched by adding water (50 mL), extracted with DCM (3*100 mL), and concentrated on a rotary evaporator to afford 2-amino-4,6-difluorobenzamide (0.25 g, 50%)
  • 2
  • [ 893428-66-5 ]
  • [ 1039948-89-4 ]
  • [ 1246250-74-7 ]
YieldReaction ConditionsOperation in experiment
79% With toluene-4-sulfonic acid; sodium hydrogensulfite; In N,N-dimethyl acetamide; at 120℃; for 16.0h; A mixture of 2-amino-4,6-difluoro-benzamide (0.96 g, 5.60 mmol), <strong>[1039948-89-4]4-(2-hydroxy-ethoxy)-3,5-dimethyl-benzaldehyde</strong> (1.09 g, 5.60 mmol), NaHSO3 (58.5 wt %, 1.00 g, 5.60 mmol) and p-toluenesulfonic acid monohydrate (1.44 g, 7.06 mmol) in N,N-dimethylacetamide (25 mL) was stirred at 120 C. for 16 hours, then cooled to room temperature. Solvent was removed under reduced pressure. The residue was diluted with water (100 mL). The solid separated was filtered and washed with water and dried under vacuum to give 5,7-difluoro-2-[4-(2-hydroxy-ethoxy)-3,5-dimethyl-phenyl]-3H-quinazolin-4-one as a white solid. Yield: 1.55 g (79%)
79% With toluene-4-sulfonic acid; sodium hydrogensulfite; In N,N-dimethyl acetamide; at 120℃; for 16.0h; Example 86 Preparation of 2-(3,5-Dimethyl-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-7-fluoro-5-(pyrrolidin-1-yl)quinazolin-4(3H)-one A mixture of 2-amino-4,6-difluoro-benzamide (0.96 g, 5.60 mmol), <strong>[1039948-89-4]4-(2-hydroxy-ethoxy)-3,5-dimethyl-benzaldehyde</strong> (1.09 g, 5.60 mmol), NaHSO3 (58.5 wt %, 1.00 g, 5.60 mmol) and p-toluenesulfonic acid monohydrate (1.44 g, 7.06 mmol) in N,N-dimethylacetamide (25 mL) was stirred at 120 C. for 16 hours, then cooled to room temperature. Solvent was removed under reduced pressure. The residue was diluted with water (100 mL). The solid separated was filtered and washed with water and dried under vacuum to give 5,7-difluoro-2-[4-(2-hydroxy-ethoxy)-3,5-dimethyl-phenyl]-3H-quinazolin-4-one as a white solid. Yield: 1.55 g (79%).
 

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