Structure of 5234-26-4
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CAS No. : | 5234-26-4 |
Formula : | C10H11NO2 |
M.W : | 177.20 |
SMILES Code : | CC(NC1=CC=CC=C1C(C)=O)=O |
MDL No. : | MFCD00032277 |
Boiling Point : | No data available |
InChI Key : | YSZGCNKBKQQPAH-UHFFFAOYSA-N |
Pubchem ID : | 21306 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H312-H332 |
Precautionary Statements: | P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P330-P363-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 |
---|---|---|
60% | 7.25 g [0.05 mol] of 2,3-dimethylindole were taken up in 180 ml of methanol and 20 ml of butyl acetate. The solution was placed in a double-walled vessel and cooled to -200C. After a constant ozone/oxygen stream of 38 g/standard m3 had been established, the ozonolysis was commenced. After the ozonolysis was complete, the reaction solution was added dropwise to an ice-cooled methanolic dimethyl sulfide solution {3.4 g (4.1 ml), [0.055 mol] of dimethyl sulfide in 100 ml of methanol} over a period of 1 hour. The reaction solution was then warmed to room temperature and the solvent was subsequently distilled off. The residue was taken up in 100 ml of methanol and the product was crystallized out at 0C.Yield: 5.31 g (60% of theory), 99.8% (GC-% by area), sand-colored to light-brown powder EPO <DP n="10"/>1H-NMR: 300 MHz (CDCI3); 2.22 (s, 3H); 2.65 (s, 3H); 7.12 (t, 1 H); 7.56 {t, 1 H); 7.83 (of, 1 H); 8.65 (of, 1 H)13C-NMR: 75.47 MHz (CDCI3); 25.51 ; 28.59; 120.6; 121.6; 122.2; 131.6; 135.1 ; 169.5; 202.8GC-MS (m/e): 177 [M+], 162, 144, 135, 120 (100%), 106, 92, 77, 65, 51 , 43 | |
60% | 10.0 g [0.0689 mol] of 2,3-dimethylindole were taken up in 200 ml of methanol. The solution was placed in a double-walled vessel and cooled to -2O0C. After a constant ozone/oxygen stream of 36 g/standard m3 had been established, the ozonolysis was commenced. After the ozonolysis was complete, the reaction solution was added dropwise to an ice-cooled methanolic thiodiethanol solution {10.1 g [0.083 mol] of thiodiethanol in 100 ml of methanol} over a period of 1 hour.The reaction solution was then warmed to room temperature, part of the solvent was distilled off (leaving 110 ml) and the product was crystallized out at 00C. The precipitated solid was filtered off with suction on a sintered glass filter (pore size 3) and washed with 25 ml of cyclohexane.Yield: 7.3 g (60% of theory), 99.5% (GC-% by area), sand-colored, light-brown powder1H-NMR: 300 MHz (CDCI3); 2.22 (s, 3H); 2.65 (s, 3H); 7.12 (t, 1 H); 7.56 (., 1 H); 7.83 (d, 1 H); 8.65 (of, 1 H)13C-NMR: 75.47 MHz (CDCI3); 25.51 ; 28.59; 120.6; 121.6; 122.2; 131.6; 135.1 ; 169.5; 202.8GC-MS (m/e): 177 [M+], 162, 144, 135, 120 (100%), 106, 92, 77, 65, 51 , 43 | |
50% | 17.O g [0.117 mol] of 2,3-dimethylindole were taken up in 180 ml of methanol and 20 ml of butyl acetate. The solution was placed in a double-walled vessel and cooled to -2O0C. After a constant ozone/oxygen stream of 36 g/standard m3 had been established, the ozonolysis was commenced. After the ozonolysis was complete, the reaction solution was added dropwise to an ice-cooled methanolic thiodiethanol solution {15.7 g [0.128 mol] of thiodiethanol in 100 ml of methanol} over a period of 1 hour. The reaction solution was then warmed to room temperature and part of the solvent was subsequently distilled off (leaving 110 ml) and the product was crystallized out at 00C. The precipitated solid was filtered off with suction on a sintered glass filter (pore size 3) and washed with 25 ml of cyclohexane (technical grade) and subsequently dried under reduced pressure.Yield: 9 g (50% of theory), 99.8% (GC-% by area), sand-colored, light-brown powder1H-NMR: 300 MHz (CDCI3); 2.22 (s, 3H); 2.65 (s, 3H); 7.12 (., 1 H); 7.56 {t, 1 H); 7.83 (d, 1 H); 8.65 (d, 1 H)13C-NMR: 75.47 MHz (CDCI3); 25.51 ; 28.59; 120.6; 121.6; 122.2; 131.6; 135.1 ; 169.5; 202.8GC-MS (m/e): 177 [M+], 162, 144, 135, 120 (100%), 106, 92, 77, 65, 51 , 43 |
Example 310.9 g of 2,3-dimethylindole were dissolved in 250 ml of ethylene glycol. 0.9 g of sodium molybdate and 1.5 g of water were added. The mixture was then heated to 500C. 5.2 equivalents of hydrogen peroxide were metered in over a period of 17 hours. The peroxide-containing solution was reduced by means of sodium sulfite/water, the precipitated sodium sulfate was filtered off and the reaction mixture was extracted with MTBE (twice with 150 ml each time). The combined organic extracts were then evaporated. The residue was taken up in 30 ml of methanol and the product was crystallized out at O0C. EPO <DP n="10"/>This gave 2-(N-acetylamino)acetophenone having a purity of 97.5%.; Example 5:10.9 g of 2,3-dimethylindole were dissolved in 250 ml of ethylene glycol. 0.9 g of sodium molybdate and 1.5 g of water were added. The mixture was then heated to 70C. 5.2 equivalents of hydrogen peroxide were metered in over a period of 17 hours. The peroxide-containing solution was reduced by means of sodium sulfite/water, the precipitated sodium sulfate was filtered off and the reaction mixture was extracted with MTBE (twice with 150 ml each time). The combined organic extracts were then evaporated. The residue was taken up in 30 ml of methanol and the product was crystallized out at 00C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetic acid; at 70℃; for 0.5h; | [0619] Acetic anhydride (10 ml) was added to a solution of 2'-aminoacetophenone (2.00 ml, 16.2 mmol) in acetic acid (10 ml) and heated at 70 C. for a half-hour. Allowed to cool and quenched with ice water (150 ml). The resultant white solid was filtered, washed with ice-water, dried under high vacuum to give 2.75 g of solid which displayed an NMR spectrum identical to that described in Adam, et. al, J. Org. Chem, 59, 2733-2739 (1994) and was used without any further purification. | |
With dmap; at 70℃; for 6h; | A mixture of 2-amino acetophenone (0.1 mol, 13.5 gm), 15 ml of acetic anhydride and a pinch of DMAP was stirred at 70C in an oil bath for 6 h. The completion of reaction was monitored by TLC. The reaction mixture on completion was poured onto ice and the precipitates were collected and crystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With bromine; In diethyl ether; acetic acid; | Example 34B N-(2-acetyl-4-bromophenyl)acetamide A solution Example 34A (6.5 g, 37 mmol) in acetic acid (100 mL) at room temperature was treated with Br2 (4 mL, 84 mmol), stirred for 1 hour and 15 minutes, poured into water (200 mL), and filtered. The solid was washed with water (2*100 mL), and hexanes (2*100 mL), dissolved in diethyl ether, washed with brine (50 mL), and concentrated to provide the desired product (8.5 g, 89%). |
89% | With bromine; In acetic acid; at 20℃; for 1.25h; | Example 34B N-(2-acetyl-4-bromophenyl)acetamide A solution Example 34A (6.5 g, 37 mmol) in acetic acid (100 mL) at room temperature was treated with Br2 (4 mL, 84 mmol), stirred for 1 hour and 15 minutes, poured into water (200 mL), and filtered. The solid was washed with water (2*100 mL), and hexanes (2*100 mL), dissolved in diethyl ether, washed with brine (50 mL), and concentrated to provide the desired product (8.5 g, 89%). |
89% | With bromine; acetic acid; at 20℃; for 2h; | N- (2-acetylphenyl) acetamide (2.66 g, 14.8 mmol)In acetic acid (40 mL), bromine (1.52 mL, 29.6 mmol) was added and the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into water,Precipitates were collected by filtration. The resulting solid was washed with water and hexane to give the title compound (3.37 g, 89%). Light yellow solid |
86% | With bromine; In acetic acid; at 20℃; for 2.33333h;Inert atmosphere; | Under N2, a pale yellow suspension of crude <strong>[5234-26-4]N-(2-acetylphenyl)acetamide</strong>(28 g, 158 mmol) in AcOH (300 mL) was stirred for about 5 min, and Br2 (12.95 mL, 253 mmol) was added within 1 h at room temperature. The resulting mixture was then stirred at room temperature for 75 min. After the reaction went to completion as monitored by LC-MS, the reaction mixture was quenched with H2O (200 mL). The mixture was filtered through Buchner funnel, and the solid was collected as N-(2- acetyl-4-bromophenyl)acetamide (35g, yield 86%). MS (m/z): 216 (M+H)+. |
86% | With bromine; In acetic acid; at 20℃; for 2.33333h;Inert atmosphere; | Under N2, a pale yellow suspension of crude <strong>[5234-26-4]N-(2-acetylphenyl)acetamide</strong> (28 g, 158 mmol) in AcOH (300 mL) was stirred for about 5 min, and Br2 (12.95 mL, 253 mmol) was added within 1 h at room temperature. The resulting mixture was then stirred at room temperature for 75 min. After the reaction went to completion as monitored by LC-MS, the reaction mixture was quenched with H2O (200 mL). The mixture was filtered through Buchner funnel, and the solid was collected as N-(2-acetyl-4-bromophenyl)acetamide (35 g, yield 86%). MS (m/z): 216 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; nitric acid; at -20 - 0℃; | Step 2: N-(2-Acetyl-6-nitro-phenyl)-acetamide; A solution of N-(2-acetyl-phenyl)-acetamide (1 g, 5.65 mmol) in cone. H2SO4 (2.8 ml_, 45.2 mmol) was cooled to -200C and fuming nitric acid (2 ml_, 33 mmol) was slowly added. The reaction mixture was warmed to 00C and stirred for 7 h. After completion of the starting material, the reaction mixture was quenched with water and extracted with dichloromethane (2X25 ml_). The combined organic layers were washed with brine and water, then dried over anhydrous sodium sulphate and concontrated to dryness. The resulting residue was purified by column chromatography using 1 %methanol in chloroform to get the title compound as yellow solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine; In dichloromethane; | Example 34A N-(2-acetylphenyl)acetamide A solution of 2'-aminoacetophenone (5.0 g, 37 mmol) in dichloromethane (150 mL) at room temperature was treated with triethylamine (5.3 mL, 40 mmol) and acetyl chloride (3.2 mL, 45 mmol), stirred for 3 hours, then washed with water. The aqueous layer was extracted with ethyl acetate (2*20 mL) and the combined extracts were concentrated to provide the desired product (6.5 g, 100%). |
100% | With triethylamine; In dichloromethane; at 20℃; for 3h; | Example 34A N-(2-acetylphenyl)acetamide A solution of 2'-aminoacetophenone (5.0 g, 37 mmol) in dichloromethane (150 mL) at room temperature was treated with triethylamine (5.3 mL, 40 mmol) and acetyl chloride (3.2 mL, 45 mmol), stirred for 3 hours, then washed with water. The aqueous layer was extracted with ethyl acetate (2*20 mL) and the combined extracts were concentrated to provide the desired product (6.5 g, 100%). |
100% | With triethylamine; In dichloromethane; at 0 - 20℃; for 4h; | 2'-aminoacetophenone (2 g, 14.8 mmol),Triethylamine (2.22 mL, 16.3 mmol) in dichloromethane (60 mL) was cooled to 0 C., acetyl chloride (1.26 mL, 17.8 mmol), and the mixture was stirred at room temperature for 4 hours.The reaction solution was washed with water and the aqueous layer was extracted with ethyl acetate.The combined organic layer was dried over anhydrous magnesium sulfate,Filtration and evaporation of the solvent gave the title compound (2.66 g, quant.).Pale yellow solid |
89% | With triethylamine; In dichloromethane; at 0 - 20℃; for 0.5h; | A solution of 2-aminoacetopheone (2.0 g, 14.8 mmol) in DCM (80 mL) was cooled to0 C, and TEA (2.4 mL) and acetyl chloride (2.06 mL, 30 mmol) were added. The resultingsolution was stirred at r.t. for 30 min. NaHCO3 was added and the solution was extracted;the organic layers were then washed with HCl (1M) and brine. The organic layers weredried (MgSO4), filtered and evaporated in vacuo to yield the desired product as a brownsolid, 2.3 g, 89% yield. R.f. 0.49 (EtOAc), m.p. 68-70 C, LCMS: tr = 1.32 min (80% MeOHin water), m/z M-H 175.79, HPLC: tr = 1.60 min (90% acetonitrile in H2O), 94%, 1H NMR(CDCl3, 270 MHz,): 2.15 (3H, s, CH3), 2.58, (3H, s, CH3), 6.99-7.06 (1H, m, ArH), 7.43-7.49(1H, m, ArH), 7.80 (1H, dd, J = 1.5, 8.15 Hz, ArH), 8.65 (1H, dd, J = 1.0, 8.4 Hz, ArH), 11.63(1H, br.s, NH). 13C NMR (CDCl3, 68 MHz): 25.7, 28.8 (CH3), 120.8 (ArCH), 121.7 (ArC),122.4, 131.7, 135.3 (ArCH), 141.1 (ArC), 169.6, 202.9 (CO). HRMS: Calcd. for C10H11NO2(M + H)+ 178.0863, found (M + H)+ 178.0858. |
84.7% | With triethylamine; In dichloromethane; at 0 - 20℃; for 3h; | 4.05 g (0.03 mol) of 2-aminoacetophenone (A1) was dissolved in 100 ml of dichloromethane. Further, 5.3 ml (0.04 mol) of triethylamine was added, and 3.5 ml (0.05 mol) of acetyl chloride was added dropwise with stirring at 0 C to 10 C. After the dropwise addition, the reaction was stirred at room temperature for 3 h, and the reaction mixture was diluted with 100 ml of ethyl acetate. The organic phase is separated and washed until the organic layer is colorless. The mixture was washed once with 30 ml of brine, and the organic phase was dried over anhydrous magnesium sulfate. After filtering off the desiccant and concentrating under reduced pressure, B1 was obtained as a white solid, yield 4.50 g, yield 84.7% |
In 1,1-dichloroethane; at 20℃;Cooling with ice; | Step 1: N-(2-Acetyl-phenyl)-acetamide; To an ice cold slurry of the 1-(2-amino-phenyl)-ethanone (2 g, 14.79 mmol) in dichloroethane (10 ml_), acetyl chloride (1.22 g, 16.2 mmol) was added slowly. The reaction mixture was warmed to room temperature and stirred for 2h. After completion of the reaction, the reaction mixture was quenched with water (10 ml.) and extracted with dichloromethane (2X25 ml_). The combined organic layers were washed with an aq. solution of 5% NaHCO3 followed by water and brine, then dried over anhydrous sodium sulphate and concentrated to dryness. The obtained residue was purified by column chromatography using 2% ethyl acetate in hexane to obtain the title compound as off- white solid which directly used for the next reaction. | |
With triethylamine; In dichloromethane; at 0 - 20℃; for 2h; | To a white suspension of 1 -(2-aminophenyl)ethanone (25 g, 185 mmol) and Et3N (33.4 mL, 240 mmol) in DCM at 0C was added dropwise AcCI (15.70 mL, 222 mmol) in 25 mL DCM. The reaction mixture was then stirred at r.t. for 2 h. After the reaction went to completion as monitored by LC-MS, the reaction mixture was cooled to 0C, and was then quenched with H2O (100 mL). The organic phase was isolated; the aqueous layer was extracted with DCM. The organic phases were combined, and washed with H2O and brine. The resulting organic phase was dried over anhydrous MgSO4, filtered and concentrated to dryness to give crude N-(2- acetylphenyl)acetamide, which was used in the next step without further purification (30g, yield 92%). MS (m/z): 136 (M+H)+. | |
With pyridine; In dichloromethane; at 0 - 20℃; for 3.25h;Inert atmosphere; | General procedure: To a solution of the appropriate 1-(2-aminophenyl)ketone (1.0mmol) and pyridine (0.48mL, 6.0mmol) in dichloromethane (5mL) was added acetyl chloride (1.2mmol) in dichloromethane (2mL) in a dropwise manner at 0C under a nitrogen atmosphere. The resulting solution was stirred for 0.25h at 0C and then brought up to room temperature slowly and monitored to completion by TLC analysis. After 3h, the reaction mixture was quenched with 10% aqueous HCl solution and the aqueous solution was extracted with dichloromethane (3×10mL). The combined organic layers were washed with brine (10mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure to afforded the 1-(2-acetylaminophenyl)ketone adduct, which was dried under reduced pressure for 5h. The ketone (0.51mmol) was dissolved in anhydrous THF (8mL) and a solution of ethynylmagnesium bromide (0.5M THF solution; 1.5mmol) was added at room temperature. The resulting mixture was allowed to reflux for 3h. On completion, the reaction mixture was cooled to room temperature and treated with saturated NH4Cl (7mL). After additional stirring at room temperature for 10min, EtOAc (15mL) was added and the phases were separated. The aqueous phase was extracted with EtOAc (3×5mL) and the combined organic layers were washed with brine (10mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure. Purification by flash column chromatography on silica gel (10% EtOAc/n-hexane as eluent) gave the title compound. | |
With triethylamine; In dichloromethane; at 0 - 20℃; for 2h; | 2-(4-(8-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1H-imidazo[4,5-c]cinnolin-1-yl)phenyl)-2-methylpropanenitrile To a white suspension of 1-(2-aminophenyl)ethanone (25 g, 185 mmol) and Et3N (33.4 mL, 240 mmol) in DCM at 0 C. was added dropwise AcCl (15.70 mL, 222 mmol) in 25 mL DCM. The reaction mixture was then stirred at r.t. for 2 h. After the reaction went to completion as monitored by LC-MS, the reaction mixture was cooled to 0 C., and was then quenched with H2O (100 mL). The organic phase was isolated; the aqueous layer was extracted with DCM. The organic phases were combined, and washed with H2O and brine. The resulting organic phase was dried over anhydrous MgSO4, filtered and concentrated to dryness to give crude N-(2-acetylphenyl)acetamide, which was used in the next step without further purification (30 g, yield 92%). MS (m/z): 136 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With sodium hydroxide; In methanol; water; at 20℃; for 6h; | General procedure: An aqueous solution of NaOH (5%, 4 ml) was added slowly to the stirring solution of appropriate aryl aldehyde (1mmol) and <strong>[5234-26-4]N-(2-acetylphenyl)acetamide</strong> (1 mmol) in methanol (20 ml) in a 100 ml conical flask. The stirring was continued at room temperature for 6 hours and the completion of reaction was monitored by TLC. The reaction on completion was poured onto ice cold water, yellow solid was obtained after filteration which was recrystallized from ethanol. The physical data for the characterstic compound is shown below. |
64.4% | With sodium hydroxide; In methanol; at 0℃; for 8h; | 5.31 g (0.03 mol) of 2-acetamidoacetophenone (B1) was dissolved in 100 ml of methanol, Then add 3.18 (0.03 mol) benzaldehyde, and add 30 ml of 5% sodium hydroxide solution dropwise under ice cooling. After the dropwise addition, the reaction was carried out at 0 C for 8 h, and the reaction liquid was poured into 250 ml of ice water to precipitate a large amount of pale yellow solid. Filter by suction, wash the filter cake, dry, C1 is obtained as a pale yellow solid, the yield is 5.09 g, the yield is 64.4%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In methanol; water; at 20℃; for 6h; | General procedure: An aqueous solution of NaOH (5%, 4 ml) was added slowly to the stirring solution of appropriate aryl aldehyde (1mmol) and <strong>[5234-26-4]N-(2-acetylphenyl)acetamide</strong> (1 mmol) in methanol (20 ml) in a 100 ml conical flask. The stirring was continued at room temperature for 6 hours and the completion of reaction was monitored by TLC. The reaction on completion was poured onto ice cold water, yellow solid was obtained after filteration which was recrystallized from ethanol. The physical data for the characterstic compound is shown below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | 5 g of 2-(λ/-acetylamino)acetophenone were taken up in 100 ml of 1.2N hydrochloric acid and stirred at reflux temperature for 6 hours. After cooling to room temperature, the pH was set to 10 by means of 40% strength sodium hydroxide and the reaction mixture was stirred with 100 ml of MTBE (MTBE = methyl tert-butyl ether). The organic phase was dried over sodium sulfate and evaporated on a rotary evaporator. This gave a light-brown oil. EPO <DP n="12"/>Yield: 2.7 g (69% of theory), reddish brown oil1H-NMR: 300 MHz (CDCI3); 2.55 (s, 3H); 6.3 φrs, 2H); 6.28 (m, 2H); 7.24 {t, 1 H); 7.68 (f, 1 H)13C-NMR: 75.47 MHz (CDCI3); 28, 115, 117, 132, 134, 170 GC-MS (m/e): 135 [M+], 120 (100%), 106, 92, 85, 77, 65, 52, 39 |
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