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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.
2-Phenylacetophenone is a photoinitiator widely used in photochemistry and polymerization reactions to enhance the polymerization efficiency of materials. And 2-Phenylacetophenone has broad-spectrum efflux pump inhibition activity.
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CAS No. : | 451-40-1 |
Formula : | C14H12O |
M.W : | 196.24 |
SMILES Code : | O=C(C1=CC=CC=C1)CC2=CC=CC=C2 |
MDL No. : | MFCD00003081 |
InChI Key : | OTKCEEWUXHVZQI-UHFFFAOYSA-N |
Pubchem ID : | 9948 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
93% | With sulfuric acid; In ethanol;Reflux; Inert atmosphere; | Example 53. Synthesis of 2,3-diphenyl-1 H-indole. Phenyl hydrazine (10.2 mL, 0.52 mol, 1 eq), 2-phenylacetophenone (20.3 g, 0.52 mol, 1 eq) and concentrated sulfuric acid (1 1.0 mL, 1.04 mol, 2 eq) were added with 100 mL ethanol in a 500 mL two neck flask. The reaction mixture was refluxed overnight under inert atmosphere. Completion of the reaction was monitored by thin layer chromatography (TLC) using as diluent ethyl acetate: heptane 1 :9. After cooling, the mixture was precipitated in 1 .5L ice in water and filtered. The obtained solid was recrystallized in water:ethanol (1 :2) to yield 2,3-diphenyl-1 H- indole as brown crystals (25.94 g, 0.096 mmol, 93 percent). Bruto formula: C2oH15N Molecular weight: 269.35 g mol"1 LC-MS (m/z): 270.1 [MH]+ RF. value (ethyl acetate:heptane 1 :9): 0.30 1H-NMR (300 MHz, DMSO-d6): delta (ppm) = 7.04 (t, 1 H, NH-C-CH-CH-CH), 7.16 (t, 1 H, NH-C-CH- CH), 7.25-7.44 (m, 8H, ArH) 7.45-7.51 (m, 4H, ArH), 1 1 .56 (s, 1 H, NH) 13C-NMR (125 MHz, DMSO-d6): delta (ppm) = 1 1 1 .40 (CH), 1 13.21 (C), 1 18.48 (CH), 1 19.61 (CH), 121 .89 (CH), 125.95 (CH), 127.38 (CH), 127.89 (C), 128.08 (CH), 128.37 (CH), 128.51 (CH), 129.66 (CH), 132.39 (C), 133.99 (C), 135.21 (C), 136.02 (C) Example 54. Synthesis of 3-(4-nitrophenyl)-2-phenyl-1 H-indole (1 st method) |
74% | With Amberlite® IR 120; In ethanol; at 80℃; for 12h; | General procedure: A mixture of the carbonyl compound (5, 1.0 mmol), arylhydrazine (6, 1.2 mmol), and the solid acid (7, Amberlite, 1.5 g, obtained from Aldrich Chemical Co.) was refluxed in absolute ethanol (10 ml) for 8 h. The reaction was monitored by thin-layer chromatography(TLC), and upon completion the mixture was cooled to room temperature, the catalyst filtered off, and the product was washed thoroughly with ethylacetate (30 ml). The combined organics were washed with water, dried (Na2SO4), and concentrated in vacuo. The resulting residue was chromatographed on a silicagel column eluting with ethylacetate?hexane mixtures to obtain the purified indole (8). This was fully characterized by infrared, 400-MHz 1H NMR, high-resolution mass spectrometry, and melting point (solids). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | <strong>[33906-30-8]2-hydrazinobenzoic acid hydrochloride</strong> (5.00 g, 30.08 mmol) and deoxybenzoin (5.90 g, 30.08 mmol) was refluxed in ACOH (100 ml) for 30 min, cone. HCI (50 ml) was added and mixture refluxed for 4 h. Water (800 ml) was added and a white solid precipitated. The solid was filtered, washed with water and recryst. from EtOAc (100 ml). Yield 2.23 g (24%); white solid. Mp. 262 C. 'H NMR (400 MHz, DMSO-d6) 6 7. 18 (t, J=8 Hz, 1 H), 7.27-7. 47 (M, 10 H), 7.75 (d, J=8 Hz, 1 H), 7.82 (d, J=8 Hz, 1 H), 10.73 (s, 1 H), 13.19 (s, 1 H). 13C NMR (100 MHz, DMSO-d6) 8 113. 80,113. 99,119. 68,124. 08,124. 72,126. 47,127. 97,128. 48,128. 72, 129.36, 129.86, 131.69, 134.35, 135.05, 135.38, 167.94. Found: 313.1117 (M). Calc. for C2LHL5NO2 : 313.1103. CAS [197313-74-9]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13% | With cycl-isopropylidene malonate; acetic acid;Reflux; | [00159] A mixture of 1,2-diphenylethanone (150 mg, 0.76 mmol), 3-ethoxy-4- hydroxy- 5 -nitrobenzaldehyde (194 mg, 0.92 mmol), meldrum's acid (132 mg, 0.92 mmol) and ammonium acetate (71 mg, 0.92 mmol) in acetic acid (5 mL) was refluxed overnight. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (EtOAc : PE=2: 1) and prep-HPLC (0.1% TFA as additive) to afford Compound 1 as yellow solid (40 mg, yield: 13%). 1H NMR (DMSO- 6 300 MHz): delta 10.20 (s, 1H), 9.60 (s, 1H), 7.47 (d, J = 3.0 Hz, 1H), 7.24-7.18 (m, 6H), 7.01-6.96 (m, 3H), 6.79 (d, J = 8.1 Hz, 2H), 4.06 (q, J = 6.0 Hz, 2H), 3.96 (d, J = 5.1 Hz, 1H), 3.14-3.07 (m, 2H),1.31 (t, J = 1.2 Hz, 3H); MS (ESI): m/z 430.9 [M+H+]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With hydrogenchloride; In ethanol; water; for 72.0h;Reflux; | 00146] To a mixture of compound 1,2-diphenylethanone (557 mg, 2.8 mmol), 3- ethoxy-4-hydroxy-5-nitrobenzaldehyde (500 mg, 2.4 mmol), and urea (427 mg, 7.1 mmol) in EtOH (50 mL) was added concentrated HCl (0.24 mL), and the reaction mixture was heated at reflux for three days. TLC (EtOAc: MeOH=10: l) showed that the starting materials were consumed. The reaction mixture was concentrated and purified by column chromatography (EtOAc: MeOH=30: l) to afford Compound 1 as a yellow solid (500 mg, yield: 49.0%). 1H NMR (DMSO- 6 400 MHz): delta 10.25 (s, 1H), 8.70 (s, 1H), 7.50 (s, 1H), 7.42 (d, J = 2.0 Hz, 1H), 7.15-7.25 (m, 6H), 6.95-7.05 (m, 3H), 6.80 (d, J = 6.4 Hz, 2H), 5.15 (d, J = 2.8 Hz, 1H), 4.05 (m, 2H), 1.30 (t, J = 6.8 Hz, 3H); MS (ESI): m/z 432.2 [M+l]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With hydrogenchloride; In ethanol; water; at 95.0℃; for 50.0h;Inert atmosphere; | [00305] Step 1: Synthesis of 4-(3-bromo-5-fluoro-4-hydroxyphenyl)-5,6-diphenyl- 3,4-dihydropyrimidin-2(lH)-one: To a mixture of 3-bromo-5-fluoro-4- hydroxybenzaldehyde (Intermediate 77) (600 mg, 2.7 mmol), 1,2-diphenylethanone (538 mg, 2.7 mmol), urea (493 mg, 8.2 mmol) and cone HC1 (1 mL) in ethanol (4 mL) was heated at 95C for 50 hours. The mixture was evaporated under reduced pressure and was purified by silica gel column chromatography (petroleum ether/ethyl acetate =2: 1) to give product (400 mg, yield 33%) as yellow solid. 1H NMR (DMSO 300MHz) : deltaIotaOmicronLambdaIota (brs, 1H), 8.66 (s, 1H), 7.45 (s, 1H), 7.24-6.95 (m, 10H), 6.75 (d, J = 7.8 Hz, 2H), 5.07 (s, 1H). [00306] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.9% | With hydrogenchloride; In ethanol; water; at 78℃; for 76.0h; | [00153] A mixture of <strong>[178686-24-3]3-ethoxy-4-hydroxy-5-nitrobenzaldehyde</strong> (323 mg, 1.53 mmol),1,2-diphenylethanone (300 mg, 1.53 mmol), thiourea (349.16 mg, 4.59 mmol), concentrated HCl solution (0.8 mL) in ethanol (10 mL) was refluxed at 78C for 76 h. After being cooled down to room temperature, the mixture was evaporated under reduced pressure, and the residue was purified by preparative HPLC to give Compound 8 (20 mg, yield 2.9%). IH NMR (CD3CN) : delta 7.68 (s, IH), 7.65 (s, IH), 7.31 (m, 4H), 7.21 (s, IH), 7.09 (m, 3H), 6.94 (m, 2H), 5.34 (s, IH), 4.11 (q, J = 7.2 Hz, 2H), 1.43- 1.40 (t, J = 7.2 Hz, 3H); MS (ESI): m/z 447.9 [M+l]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25.45% | [00265] A mixture of 1,2-diphenylethanone (500 mg, 2.55 mmol), 3-ethoxy-4- hydroxy- 5 -nitrobenzaldehyde (538.5 mg, 2.55 mmol), guanidine hydrochloride (731 mg, 7.65 mmol), diisopropylamine (1.1 mL) in ethanol (5 mL) was refluxed at 80C for 60 h. The mixture was evaporated under reduced pressure and the residue was treated with a mixture of saturated aqueous sodium bisulfite solution (50 mL), dichloromethane (100 mL) and isopropanol (30 mL), and the resulting mixture was stirred at room temperature for 30 min. The organic layer was separated and the aqueous layer was extracted with a mixture of dichloromethane and isopropanol (3: 1, 50 mLx2). The combined organic layer was dried over anhydrous sodium sulfate and purified by preparative HPLC. The product containing fractions were treated with HCl/MeOH (2 mL, 2 N) and concentrated in vacuo to give Compound 112 as an HC1 salt (280 mg, yield 25.45%). 1H NMR (DMSO- d6 400MHZ): delta 10.48 (s, IH), 10.27 (s, IH), 9.35 (s, IH), 7.59 (s, 2H), 7.53 (s, IH), 7.52-7.31 (m, 5H), 7.26 (d, J = 2.0 Hz, 1H), 7.12-7.10 (m, 3H), 6.92-6.90 (m, 2H), 5.57 (d, J = 3.2 Hz, 1H), 4.1-4.06 (q, J = 7.2 Hz, 2H), 1.36-1.32 (t, J = 7.2 Hz, 3H); MS (ESI): m/z 431.0 [M + H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15.2% | With hydrogenchloride; In ethanol; water; for 72.0h;Reflux; | [00156] A mixture of 1,2-diphenylethanone (400 mg, 2.04 mmol), 3-ethoxy-4- hydroxy- 5 -nitrobenzaldehyde (430 mg, 2.04 mmol), and 1-methylurea (454 mg, 6.12 mmol) in anhydrous EtOH was added concentrated HC1 (204 mg, 2.04 mmol), and the reaction mixture was refluxed for 3 days. When TLC (EtOAc:MeOH=10: l) showed that the starting materials were consumed, the reaction mixture was concentrated, and purified by preparative HPLC to afford Compound 11 as a yellow solid (138 mg, yield: 15.2%). 1H NMR (DMSO- d6 400 MHz TMS): delta 10.25 (s, 1H), 7.68 (d, J = 2.8 Hz, 1H), 7.45 (s, 1H), 7.20-7.28 (m, 3H), 7.15-7.20 (m, 3H), 6.85-6.95 (m, 3H), 6.70 (d, J = 6.4 Hz, 1H), 5.00 (d, J = 2.4 Hz, 1H), 4.02 (m, 2H), 2.60 (s, 3H), 1.30 (t, J = 7.0 Hz, 3H); MS (ESI): m/z 446.2 [M+l]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11.6% | With chloro-trimethyl-silane; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; | 00186] A mixture of 1,2-diphenylethanone (300 mg, 1.53 mmol), 3-ethoxy-4- hydroxy-5-nitrobenzaldehyde (324 mg, 1.53 mmol), and 1,3-dimethylurea (174 mg, 1.98 mmol) in DMF (5 mL) was added TMSC1 (1.0 g, 9.12 mmol), and the reaction mixture was stirred at room temperature overnight under nitrogen. LCMS showed that about 30% of starting materials were consumed. H20 (10 mL) was added to quench the reaction, and the aqueous layer was extracted with EtOAc (30 mLx3). The combined organic layer was washed with brine (20 mL), dried over Na2S04, filtered, and concentrated. The residue was purified by column chromatography (PE: EtOAc=l :2) and preparative HPLC to afford Compound 41 as a yellow solid (82 mg, yield: 11.6%). 1H NMR (DMSO- 6 400 MHz): |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70.6% | piperidine; In toluene;Reflux; | [00208] Step 1: To a solution of 1,2-diphenylethanone (300 mg, 1.5 mmol) and 3- ethoxy-4-hydroxy-5-nitrobenzaldehyde (324 mg, 1.5 mmol) in anhydrous toluene (10 mL) was added piperidine (cat.), and the reaction mixture was refluxed overnight. TLC (PE: EtOAc=3: l) indicated that the starting materials were consumed. The solvent was removed under vacuum, and the residue was purified by column chromatography (PE: EtOAc=10: l) to afford the intermediate as a red solid (420 mg, yield: 70.6%). 1H NMR (DMSO- 6 400 MHz): delta 10.50 (s, 1H), 7.90 (d, J = 1.4 Hz, 3H), 7.80 (d, J = 1.2 Hz, 2H), 7.58-7.61 (m, 2H), 7.25-7.7.50 (m, 21H), 7.20 (s, 1H), 7.05 (s, 1H), 6.75 (s, 1H), 3.80 (q, J = 7.2 Hz, 3H), 3.62 (q, J = 7.2 Hz, 2H), 1.17 (t, J = 3.6 Hz, 7H), 1.12 (t, J = 3.6 Hz, 3H); MS (ESI): m/z 390.1 [M+l]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With iron(III) chloride; 2,3-dicyano-5,6-dichloro-p-benzoquinone; at 60℃;Inert atmosphere; | Under an argon atmosphere and at room temperature,In the reaction tube, diphenylethanone (39.3 mg, 0.2 mmol)And 2-nitro-1,3-diphenyl ether (183 mg, 2 mmol, 10.0 eq)Was dissolved in 1,2-dichloromethane (6.0 mL), followed by the addition of DDQ (109 mg, 0.48 mmol)And FeCl3 (4.9 mg, 0.03 mmol, 0.03 eq)Placed in 60 oil bath stirring reaction,After the reaction was stopped, 1.0 mL of petroleum ether was added and the mixture was taken directly to the column. The column was separated by petroleum ether and ethyl acetate (60:40, by volume) as the mobile phase. The product was subjected to column chromatography to give 2- 3-nitrophenyl) -1,2-diphenylethanone,Amorphous solid (58%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With toluene-4-sulfonic acid; In ethanol; toluene; for 12h;Reflux; | Intermediate 1-3 (20 g 73.47 mmol) and diphenyl ethyl ketone (14.40 g 73.47 mmol) were added to a mixed solvent of toluene and ethanol (500 mL Vtoluene: VEtOH = 4:1), followed by p-toluenesulfonic acid ( 63.25g 367.35mmol), refluxing reaction for 12h, after completion of the reaction, the mixture was washed with water, extracted with DCM, dried with organic phase and purified by silica gel column chromatography to afford intermediate 1-5 (16.8 g, 85%), MW: 269.12. |