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CAS No. : | 22190-40-5 | MDL No. : | MFCD05664819 |
Formula : | C11H12BrNO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | BHQKJGRWIRTURN-UHFFFAOYSA-N |
M.W : | 254.12 | Pubchem ID : | 89622 |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
With bromine; acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With N-Bromosuccinimide In DMF (N,N-dimethyl-formamide) at 20℃; for 3h; | Crude 1- (3, 4-dihydro-2H-quinolin-1-yl)-ethanone was dissolved in DMF (60 mL), and N-bromo succinimide (100 mmol) was added portion wise. Stirred at room temperature for 3h, then the reaction mixture was poured into water (150 mL) and extracted with ethyl acetate. The organic phase was washed with NH4C1 (sat. ), dried over MgS04, filtered and evaporated. Yield: 96% 1H NMR (D6-DMSO) : 1.85 (m, 2H); 2.16 (s, 3H); 2.70 (m, 2H); 3.66 (m, 2H); 7.25- 7.60 (3H). |
90% | With N-Bromosuccinimide In dichloromethane at 0 - 45℃; for 16h; | |
90% | With N-Bromosuccinimide In dichloromethane at 0 - 45℃; for 16h; | 87.2 Step 2 To a solution of 1-(3,4-dihydro-2H-quinolin-1-yl)ethanone (400 mg,2.0 mmol)in DCM(10 mL)at 0 °C was added N-bromosuccinimide (400 mg,2.0 mmol)portionwise. The mixturewas stirred at room temperature for 2 h,then heated at 45 °C for 14 h. After cooling to roomtemperature,the reaction was concentrated under reduced pressure. The residue was purified by silica gel chromatography (100% Heptanes to 60% EtOAc in Heptanes gradient)to afford thetitle compound (0.542 g,90%)as a yellow oil. 1HNMR (400 MHz,CDCl3)8 7.40-7.03 (m,3H),3.76 (t,J = 6.5 Hz,2H),2.71 (t,J = 6.6 Hz,2H),2.22 (s,3H),2.04- 1.86 (m,2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | Stage #1: 1-(6-bromo-1,2,3,4-tetrahydroquinolin-1-yl)ethan-1-one With copper(I) cyanide In DMF (N,N-dimethyl-formamide) for 18h; Heating / reflux; Stage #2: With ammonia In DMF (N,N-dimethyl-formamide); water | 1-(6-Bromo-3, 4-dihydro-2H-quinolin-l-yl)-ethanone (96 mmol) was dissolved in DMF (60 mL) and CuCN (200 mmol) was added. The reaction mixture was refluxed for 18h, then cooled and poured into water (400 mL). Aq. NH3 (sat. ) (100 mL) was added, and the mixture was stirred vigorously until it had turned blue. The product had precipitated and was removed by filtration, washed with water and dried. Yield: 53% 1H NMR (D6-DMSO) : 1.78 (m, 2H); 2.67 (m, 2H); 3.23 (m, 2H); 6.43 (d, 1H); 7.41- 7.47 (2H). m/z: 201 (MH+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17 Methoxylation of 6-Bromo-1-Acetyl-1,2,3,4-Tetrahydroquinoline with subsequent hydrolysis to yield 6-Methoxy-1,2,3,4-Tetrahydroquinoline Hydrochloride The crude product was dissolved in isopropanol (210 ml) and treated with 16% w/w hydrogen chloride in isopropanol (125 ml). On cooling the hydrochloride salt crystallized out. Filtration and drying gave pure 6-methoxy-1,2,3,4-tetrahydroquinoline hydrochloride, m.p. 150° to 152° C. (yield 66 g: 75% of theory). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | 8 Methoxylation of 6-Bromo-1-Acetyl-1,2,3,4-Tetrahydroquinoline with subsequent hydrolysis to yield 6-Methoxy-1,2,3,4-Tetrahydroquinoline Its infra-red spectrum was identical to that of authentic material obtained by the hydrogenation of 6-methoxyquinoline. Overall yield=67%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: In 1,2-dichloro-ethane at 20℃; Inert atmosphere; Stage #2: With N-Bromosuccinimide In N,N-dimethyl-formamide | 28.1 Step 1 1-(6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-1-yl)ethan-1-one General procedure: Step 11-(6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-1-yl)ethan-1-oneTo a solution of the 2-methyl-1,2,3,4-tetrahydroquinoline (5g, 36.96 mmol) in 1,2-dichloroethane (34 mL) was added acetic anhydride (4.26 mL, 50 mmol) and the reaction stirred at ambient temperature for 4 hours under nitrogen atmosphere. A further 1 mL of acetic anhydride was added and the reaction mixture stirred overnight. The solvents were removed in vacuo to afford a liquid which was dissolved in EtOAc (60 mL) and the organic phase was then washed sequentially with water (50 mL), 1 N NaOH (aq) (50 mL), water (50 mL) and sat NaCI (aq) (50 mL), then dried over magnesium sulphate, filtered and the filtrate evaporated in vacuo to afford a yellow oil. The product was dissolved in DMF (26 mL) and N-bromosuccinimide (6.20 g, 34.86 mmol) was added in portions and mixture then stirred overnight. The reaction mixture was partitioned between EtOAc (200 mL) and water (100 mL). The organic phase was separated then washed with saturated aqueous ammonium chloride solution (100 mL) then sat. NaCI (aq) (2 x 50 mL). The reaction mixture was dried over magnesium sulphate, filtered and filtrate evaporated in vacuo to afford product as a yellow oil (9.3 g, quant.).LC/MS (method B): RT = 1.28 min; m/z = 268 [M+H]+. Total run time 1.90 mins. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With hydrogenchloride In water for 5h; Reflux; | 83.1 Step 1 6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline Step 16-bromo-2-methyl-1,2,3,4-tetrahydroquinolineTo a suspension of 1-(6-bromo-2-methyl-1 ,2,3,4-tetrahydroquinolin-1-yl)ethan-1- one (example 15, step 1) (5.16 g, 19.24 mmol) in water (15 mL) was added cone HCI (12N, 25 mL) and the mixture was heated to reflux for 5 hours then allowed to cool to ambient temperature. Further water was added and the pH of the mixture adjusted to pH = 4 by cautious addition of solid NaOH pellets. The precipitate was filtered off and washed with water then iso-hexane and dried in vacuo to afford 6-bromo-2-methyl-1 ,2,3,4-tetrahydroquinoline as an off-white solid (2.07 g, 48%).LC/MS (method B): RT = 1.41 min; m/z = 226 [M+H]+. Total run time 1.90 mins. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: hydrogenchloride / water / 5 h / Reflux 2.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide 2.2: 1.5 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: hydrogenchloride / water / 5 h / Reflux 2.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide 2.2: 1.5 h / 20 °C 3.1: tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; potassium acetate / 1,4-dioxane / 80 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: hydrogenchloride / water / 5 h / Reflux 2.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide 2.2: 1.5 h / 20 °C 3.1: tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; potassium acetate / 1,4-dioxane / 80 °C / Inert atmosphere 4.1: 1,1'-bis-(diphenylphosphino)ferrocene; potassium carbonate / water; acetonitrile / 1 h / 80 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | With dichloro(1,3-bis(2,6-bis(3-pentyl)phenyl)imidazolin-2-ylidene)(3-chloropyridyl)palladium(II); sodium t-butanolate In 1,4-dioxane at 120℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / 0 - 32 °C 2: N-Bromosuccinimide / dichloromethane / 16 h / 0 - 45 °C | ||
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2.5 h / 0 - 32 °C 2: N-Bromosuccinimide / dichloromethane / 16 h / 0 - 45 °C | ||
Multi-step reaction with 2 steps 1: N-Bromosuccinimide / N,N-dimethyl-formamide / 1 h / 0 °C 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 4 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With palladium diacetate In 1,2-dichloro-ethane at 20℃; for 10h; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 1 h / 110 °C / Microwave irradiation 2: dichloromethane / 36 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 1 h / 110 °C / Microwave irradiation 2: dichloromethane / 36 h 3: hydrogenchloride / water / 2 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.4 g | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In 1,4-dioxane at 110℃; for 1h; Microwave irradiation; | Synthesis of (l-acetyl-3,4-dihydro-2H-quinolin-6-yl)boronic acid (N-001). A mixture of 1.5 g (5.9 mmol) of l-(6-bromo-3,4-dihydro-2H-quinolin-l-yl)ethanone, 2.3 g (8.9 mmol) of bis(pinacolato)diboron, 1.7 g (19 mmol) of KOAc and 0.49 g (0.59 mmol) of Pd(dppf)- CH2CI2 in 8 ml of degasses 1,4-dioxane is heated to 110 °C with microwave irradiation for 1 h. The mixture is filtered, concentrated, and purified by flash chromatography (0-7% MeOH in CH2CI2) to provide 1.4 g (4.5 mmol) of l-[6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-3,4- dihydro-2H-quinolin- l-yl]ethanone (I-AAW). (0185) A mixture of 1.4 g (4.5 mmol) of I-AAW, 2.4 g (23 mmol) of diethanolamine, and 10 mL of CH2CI2 is stirred for 36 h. The mixture is concentrated and purified by flash chromatography (0- 10% MeOH in CH2C12) to provide 0.46 g (1.5 mmol) of l-[6-(l,3,6,2-dioxazaborocan-2-yl)-3,4- dihydro-2H-quinolin- l-yl]ethanone (I-AAX). (0186) I-AAX (0.22 g, 0.75 mmol) is stirred with 1 mL of 1M HCl for 2h. A solid is generated, that is filtered and dried to provide 0.10 g (0.46 mmol) of N-001. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 4h; | To a solution of <strong>[22190-35-8]6-bromo-1,2,3,4-tetrahydroquinoline</strong> (13.1 g, 14.6 mmol) and DIPEA (6.5 mL, 36.5 mmol) in DCM (30 mL) at 0, was added AcCl (1.72 g, 21.9 mmol) in one portion. The reaction mixture was stirred at RT for 4 h, then quenched with water. It was extracted with EA, the combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give 1-(6-bromo-3,4-dihydroquinolin -1(2H)-yl)ethan-1-one as a light- yellow oil (3.33 g, 90%). LC-MS (ESI): m/z (M+H)+ = 254.06/256.06 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium(0); sodium carbonate / 1,4-dioxane; water / 10 h / 100 °C 2: hydrogenchloride; sodium hydroxide / water; methanol; tetrahydrofuran / 12 h / 50 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 100℃; for 10h; | 12 To a solution of 1-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)ethan-1-one (1.0 g, 4.0 mmol), (4-(methoxycarbonyl)phenyl) boronic acid (1.08 g, 6.0 mmol), and Na2CO3 (850 mg, 8.0 mmol) in dioxane/H2O (10/2 mL), was added Pd(PPh3)4 (466 mg, 0.4 mmol). The mixture was stirred at 100 for 10 h. It was then extracted with EA, the combined organic layers were washed with brine, dried over Na2SO4, concentrated, and purified by flash chromatography to give methyl 4-(1-acetyl-1,2,3,4 -tetrahydroquinolin-6-yl)benzoate as a white solid (1.25 g, 100%). LC-MS (ESI): m/z (M+H)+ = 310.13. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)ethan-1-one; tert-butyl 7-(2-amino-5-(bis(4-methoxybenzyl)amino)-6-fluoroquinazolin-7-yl)-8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-1-carboxylate With tripotassium phosphate tribasic; tris-(dibenzylideneacetone)dipalladium(0); di-tert-butyl(2′,4′,6′- triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine In lithium hydroxide monohydrate; toluene at 110℃; Inert atmosphere; Stage #2: With trifluoroacetic acid In 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran for 2h; | 2A.3-2A.4 Steps 3 and 4. Synthesis of Compound 2-7. A mixture of 1-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)ethan-1-one (29 mg, 0.11 mmol), intermediate I-16 (50 mg, 0.075 mmol), t-BuBrettPhos (15 mg, 0.030 mmol), Pd2(dba)3(6.9 mg, 7.5 μmol), and K3PO4 (32 mg, 0.15 mmol) in toluene (0.75 mL) and water (10 μL) was deoxygenated by bubbling argon for 3 min, then warmed to 110 °C and stirred overnight. After cooling to to RT, filtered and concentrated. Crude reaction residue was dissolved in 1 mL of DCM, 1 mL of TFA, aged for 2 h. After concentration and the crude mixture was purified by reverse phase chromatography (15-70% ACN/water with 0.1% NH4OH) to give the desired product, 2-7.1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 9.57 (s, 1H), 7.84 (s, 1H), 7.70 (s, 2H), 7.35 (s, 1H), 6.62 (d, J = 5.7 Hz, 1H), 6.35 (s, 2H), 5.69 (s, 1H), 4.39 - 4.21 (m, 2H), 3.66 (t, J = 6.3 Hz, 2H), 3.38 (s, 2H), 2.69 (s, 2H), 2.14 (s, 3H), 1.94 (s, 3H), 1.86 (s, 2H). MS (EI) calc’d for C27H27FN7O2, [M+H]+, 500; found, 500. | |
Stage #1: 1-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)ethan-1-one; tert-butyl 7-(2-amino-5-(bis(4-methoxybenzyl)amino)-6-fluoroquinazolin-7-yl)-8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-1-carboxylate With tripotassium phosphate tribasic; tris-(dibenzylideneacetone)dipalladium(0); di-tert-butyl(2′,4′,6′- triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine In lithium hydroxide monohydrate; toluene at 110℃; Inert atmosphere; Stage #2: With trifluoroacetic acid In 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran for 2h; | 2A.3-2A.4 Steps 3 and 4. Synthesis of Compound 2-7. A mixture of 1-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)ethan-1-one (29 mg, 0.11 mmol), intermediate I-16 (50 mg, 0.075 mmol), t-BuBrettPhos (15 mg, 0.030 mmol), Pd2(dba)3(6.9 mg, 7.5 μmol), and K3PO4 (32 mg, 0.15 mmol) in toluene (0.75 mL) and water (10 μL) was deoxygenated by bubbling argon for 3 min, then warmed to 110 °C and stirred overnight. After cooling to to RT, filtered and concentrated. Crude reaction residue was dissolved in 1 mL of DCM, 1 mL of TFA, aged for 2 h. After concentration and the crude mixture was purified by reverse phase chromatography (15-70% ACN/water with 0.1% NH4OH) to give the desired product, 2-7.1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 9.57 (s, 1H), 7.84 (s, 1H), 7.70 (s, 2H), 7.35 (s, 1H), 6.62 (d, J = 5.7 Hz, 1H), 6.35 (s, 2H), 5.69 (s, 1H), 4.39 - 4.21 (m, 2H), 3.66 (t, J = 6.3 Hz, 2H), 3.38 (s, 2H), 2.69 (s, 2H), 2.14 (s, 3H), 1.94 (s, 3H), 1.86 (s, 2H). MS (EI) calc’d for C27H27FN7O2, [M+H]+, 500; found, 500. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran at 23℃; for 1h; Inert atmosphere; | 2A.1-2A.2 Steps 1 and 2. Preparation of 1-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)ethan-1-one. A solution of tert-butyl 6-bromo-3,4-dihydroquinoline-1(2H)-carboxylate, HCl (150 mg, 0.430 mmol) in DCM (2.2 mL) was treated with TFA (0.33 mL, 4.3 mmol). The reaction bubbled and allowed to age at RT for 2 h. The solvent was removed under reduced pressure to give 6-bromo-1,2,3,4-tetrahydroquinoline, TFA. The crude oil was taken up in DCM (2 mL) and added acetyl chloride (31 μL, 0.43 mmol). This was followed by the slow addition of triethylamine (0.18 mL, 1.3 mmol). The reaction was allowed to stir at 23 °C. After 1 h, the reaction was diluted with DCM and added water. The mixture was transferred to a separatory funnel and shaken up vigorously. The organic layer was separated and the organic layer was extracted with DCM (3 x 25 mL). The combined organic layer was washed with brine and then separated. The organic layer was dried over Na2SO4and then concentrated to dryness over reduced pressure. The residue was purified by chromatography on SiO2(gradient of 0-10% MeOH/DCM in 4 g silica gel) to afford 1-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)ethan-1-one. MS (EI) calc’d for C11H13BrNO [M+H]+, 254, 256; found, 254, 256. | |
With triethylamine In 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran at 23℃; for 1h; Inert atmosphere; | 2A.1-2A.2 Steps 1 and 2. Preparation of 1-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)ethan-1-one. A solution of tert-butyl 6-bromo-3,4-dihydroquinoline-1(2H)-carboxylate, HCl (150 mg, 0.430 mmol) in DCM (2.2 mL) was treated with TFA (0.33 mL, 4.3 mmol). The reaction bubbled and allowed to age at RT for 2 h. The solvent was removed under reduced pressure to give 6-bromo-1,2,3,4-tetrahydroquinoline, TFA. The crude oil was taken up in DCM (2 mL) and added acetyl chloride (31 μL, 0.43 mmol). This was followed by the slow addition of triethylamine (0.18 mL, 1.3 mmol). The reaction was allowed to stir at 23 °C. After 1 h, the reaction was diluted with DCM and added water. The mixture was transferred to a separatory funnel and shaken up vigorously. The organic layer was separated and the organic layer was extracted with DCM (3 x 25 mL). The combined organic layer was washed with brine and then separated. The organic layer was dried over Na2SO4and then concentrated to dryness over reduced pressure. The residue was purified by chromatography on SiO2(gradient of 0-10% MeOH/DCM in 4 g silica gel) to afford 1-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)ethan-1-one. MS (EI) calc’d for C11H13BrNO [M+H]+, 254, 256; found, 254, 256. |
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