Structure of 326-65-8
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 326-65-8 |
Formula : | C9H10FNO |
M.W : | 167.18 |
SMILES Code : | CC(NC1=CC=C(F)C=C1C)=O |
MDL No. : | MFCD01861997 |
InChI Key : | RJKWSTDTEPBWBJ-UHFFFAOYSA-N |
Pubchem ID : | 2737623 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P264-P270-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P330-P362-P403+P233-P501 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 1c N-(2'-Chloro-4'-fluoro-6'-methylphenyl)-4-methylaniline 3.08 g (19.3 mmol) of 2-chlor-4-fluoro-6-methyl-aniline (prepared from N-acetyl-4-fluoro-2-methylaniline by chlorination followed by hydrolyses), 3.48 g (20.3 mmol) of 4-bromotoluene are dissolved in 55 ml of toluene and after the addition of 3.43 g (36 mmol) of sodium tert-butoxide, 166 mg (0.82 mmol) of tri-tert-butylphosphin and 460 mg (0.8 mmol) of bis-dibenzylideneacetone-palladium(0), the mixture is heated with stirring under nitrogen to 90 C. for 40 minutes. The usual aqueous acidic workup (50 ml water, 10 ml conc. HC, 1 g hyflo, filtration, washing the organic phase with water, drying, evaporation) gave 5.5 g of the crude product which may be purified by flash-chromatography using silica and heptane as the eluent affording 3.52 g of N2'-chloro-4'-fluoro-6'-methylphenyl)-4-methylaniline as an oily substance. 1H-NMR (400 MHz, DMSO-d6): 2.18 (s, 3H, CH3); 6.37 (d, 2H, H-C (2, 6)]; 6.92 [d, 2H, H-C (3, 5)]; 7.19 (dd, 1H, H-C (5')]; 7.32 (s, 1H, NH); 7.35 (dd, 1H, HC (3')]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With potassium nitrate; In sulfuric acid; | Referential Example 1 4-Fluoro-2-methyl-5-nitroacetanilide To a solution of 4-fluoro-2-methylacetanilide (46.5 g, 278 mmol) in concentrated sulfuric acid (500 ml) was added dropwise a solution of potassium nitrate (141 g, 1.39 mol) in concentrated sulfuric acid (500 ml) over 2 hours at room temperature. After completion of dropwise addition, the reaction mixture was poured into ice water and the precipitated crystals were collected by filtration. These were washed with water and then air-dried, thereby obtaining 44.5 g of title compound as colorless powder. Yield 75%. 1H-NMR(DMSO-d6, δ): 2.11(3H,s), 2.32(3H,s), 7.50(1H,d,J=12.7 Hz), 8.34(1H,d,J=7.3 Hz), 9.56(1H,brs). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25.0 g (94%) | PREPARATION 14 N-(4-Fluoro-2-methylphenyl)acetamide In the manner of Preparation 5, 20 g (0.160 mol) of 5-fluoro-2-methylaniline was converted into the title compound: yield 25.0 g (94%); m.p. 131-132 C., [lit. m.p. 133.5-134 C.: E. A. Steck, L. T. Fletcher, J. Am. Chem. Soc. 70, 439-440 (1948)]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11.88 g (81%) | PREPARATION 15 2-Acetylamino-4-fluorobenzoic Acid In the manner of Preparation 6, 12.5 g (0.075 mol) of <strong>[326-65-8]N-(4-fluoro-2-methylphenyl)acetamide</strong> was transformed into the title compound: yield 11.88 g (81%); m.p. 212.5-214.5 C., [lit. m.p. 209-209.5 C.: Steck and Fletcher loc. cit.]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | With nitric acid; acetic anhydride; at 0 - 20℃; for 15.0h; | At 0 C , to a solution of N-(4- fluoro-2-methylphenyl)acetamide (2.70 g, 16.15 mmol) in acetic anhydride (60 mL), was added HNO3 (65% in water, 3.2 mL, 46.22 mmol) dropwise over 20 mm period. The resulting mixture was then stirred for 15 h at room temperature. After the reaction was done, it was quenched by the addition of ice water (100 mL) and the pH value of the resulting mixture was adJusted to 7-8 with sat. sodium bicarbonate solution. The mixture was extracted with dichloromethane (300 mL x 3). The organic phases were combined, washed with brine and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by flash chromatography eluting with EtOAc in hexane (0% to 15% gradient) to yield N-(4-fluoro-2-methyl-6- nitrophenyl)acetamide as brown solid (1.35 g, 39%). MS: m/z = 213.1 [M+Hj. |
With nitric acid; acetic anhydride; at 0 - 20℃; | Step B: N-(4-fluoro-2-methy -6-nitrophenyl)acetamide [0193] To a mixture of <strong>[326-65-8]N-(4-fluoro-2-methylphenyl)acetamide</strong> (19 g, 113.1 mmol, 1 eq) and (CH3CO)20 (190 mL) was added HN03 (11.4 mL, 1.0 eq) dropwise at 0C. The reaction mixture was allowed to warm to RT overnight and was subsequently poured onto ice and extracted with DCM. The organic phase was washed with aqueous NaHC03 until the pH of the aqueous layer was > 7. The organic phase was washed with water and then dried over Na2S04. The solvent was evaporated to give the title compound as a crude solid (20 g, 84%>). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.82 (IH, s), 7.71 (IH, dd, J;=2.8 Hz, J2=8.0 Hz), 7.56 (IH, dd, J;=2.8 Hz, J2= 9.2 Hz), 2.32 (3H, s), 2.02 (3H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | at 20℃; for 3.0h; | [0191] A mixture of 4-fhioro-2-methylaniline (20 g) and (CH3CO)20 (400 mL) was stirred at RT for 3 hours. The reaction mixture was subsequently poured into ice water (1000 mL), stirred for 10 minutes, filtered, and dried under vacuum to give the title compound (20 g, 74%). |
50% | at 20℃; for 3.0h; | 4-fluoro-2-methylaniline (3.80 g, 30.37 mmol) was added to 100 mL acetyl anhydride at room temperature. The resulting solution was stirred for 3 h at room temperature. When the reaction was done, it was quenched by the addition of water (100 mL) and the resulting mixture was extracted with dichloromethane (300 mL x 3). The organic phases were combined, washed with brine and dried over Na2SO4. The solvent was removed under reduced pressure to yield N-(4-fluoro-2-methylphenyl)acetamide as white solid (2.70 g, 50%). MS: m/z = 168.2 [M+Hj. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.56 g | With potassium fluoride; fluorosulfonyl fluoride; In dichloromethane; at 0 - 20℃; for 12.0h;Sealed tube; | Sequentially add N-acetyl-2-methylphenylhydroxylamine (1.65g, 0.010mol), KF (0.29g, 0.005mol) and dichloromethane (20mL) into a stirred 50mL reaction flask, and cool to 0C , Pass sulfonyl fluoride (2.04g, 0.020mol), seal the system, slowly warm to room temperature, stir and react for 12h, add saturated brine (10mL) to wash after the reaction is over, and concentrate the organic phase under reduced pressure to distill off dichloromethane to obtain White solid N-acetyl-2-methyl-4-fluoroaniline (1.56g), add N-acetyl-2-methyl-4-fluoroaniline to 2mol/L hydrochloric acid (20mL), heating to reflux After reacting for 12h, TLC detects the completion of the reaction, add NaOH (5mol/L) to adjust the pH to alkaline (8-10), add organic solvent dichloromethane (20mL) for extraction, and wash the organic phase with saturated brine and anhydrous sodium sulfate After drying and desolving under reduced pressure, the crude product was subjected to column chromatography to obtain pure 2-methyl-4-fluoroaniline as a yellow liquid (1.15 g, yield 92%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.15 g | With hydrogenchloride; In water; for 12.0h;Reflux; | Sequentially add N-acetyl-2-methylphenylhydroxylamine (1.65g, 0.010mol), KF (0.29g, 0.005mol) and dichloromethane (20mL) into a stirred 50mL reaction flask, and cool to 0C , Pass sulfonyl fluoride (2.04g, 0.020mol), seal the system, slowly warm to room temperature, stir and react for 12h, add saturated brine (10mL) to wash after the reaction is over, and concentrate the organic phase under reduced pressure to distill off dichloromethane to obtain White solid N-acetyl-2-methyl-4-fluoroaniline (1.56g), add N-acetyl-2-methyl-4-fluoroaniline to 2mol/L hydrochloric acid (20mL), heating to reflux After reacting for 12h, TLC detects the completion of the reaction, add NaOH (5mol/L) to adjust the pH to alkaline (8-10), add organic solvent dichloromethane (20mL) for extraction, and wash the organic phase with saturated brine and anhydrous sodium sulfate After drying and desolving under reduced pressure, the crude product was subjected to column chromatography to obtain pure 2-methyl-4-fluoroaniline as a yellow liquid (1.15 g, yield 92%). |
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