Structure of 13788-92-6
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CAS No. : | 13788-92-6 |
Formula : | C9H7BrN2 |
M.W : | 223.07 |
SMILES Code : | BrC1=CC=C(N2N=CC=C2)C=C1 |
MDL No. : | MFCD08059318 |
InChI Key : | SQCVGDMTHFQUKS-UHFFFAOYSA-N |
Pubchem ID : | 10443564 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P233-P260-P261-P264-P270-P271-P280-P301+P312-P302+P352-P304-P304+P340-P305+P351+P338-P312-P321-P330-P332+P313-P337+P313-P340-P362-P403-P403+P233-P405-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 |
---|---|---|
82% | With caesium carbonate;copper(I) oxide; trans-N,N'-bis(pyridin-2-ylmethylene)cyclohexane-1,2-diamine; In acetonitrile; at 82℃; for 72h;Conversion of starting material; | Preparation of 1-(4?-bromophenyl)-1H-pyrazole [0542] Operating protocol B (82 C., 72 hours) was followed using 117 mg of Chxn-Py-Al (0.4 mmoles), 1.887 g of 1,4-dibromobenzene (8 mmoles), 136 mg of pyrazole (3 mmoles) and 1.6 ml of acetonitrile. [0543] The degree of transformation and selectivity for 1-(4?-bromophenyl)-1H-pyrazole were 89%. [0544] The residue obtained was purified by silica gel chromatography (eluent: hexane/dichloromethane, 100/0 to 50/50). [0545] 366 mg of a colourless solid was obtained, corresponding to a yield of 82% by weight. [0546] The compound obtained had the following formula: [CHEMMOL-00046] |
82% | 14.4 mg of cuprous oxide (0.1 mmoles), 116.8 mg of Chxn-Py-Al or another ligand as generally defined in this patent (0.4 mmoles), 3 mmoles of a nucleophilic compound, 2 mmoles of arylation agent and 1.303 g of caesium carbonate (4 mmoles) are successively introduced into a 35 ml Schlenk tube that has been oven dried at 100 C. and is provided with a magnetic stirrer (12×4.5 mm) and under a nitrogen atmosphere. The Schlenk tube is purged under vacuum then refilled with nitrogen. 1.2 ml of acetonitrile or DMF is then added using a syringe. The reactor is placed in an oil bath at a temperature of 82 C. and stirred for a period of one to five days.; Operating protocol B (82 C., 72 hours) was followed using 117 mg of Chxn-Py-Al (0.4 mmoles), 1.887 g of 1,4-dibromobenzene (8 mmoles), 136 mg of pyrazole (3 mmoles) and 1.6 ml of acetonitrile. The degree of transformation and selectivity for 1-(4'-bromophenyl)-1H-pyrazole were 89%. The residue obtained was purified by silica gel chromatography (eluent: hexane/dichloromethane, 100/0 to 50/50). 366 mg of a colourless solid was obtained, corresponding to a yield of 82% by weight. The compound obtained had the following formula: The characteristics were as follows: M Pt: 71 C. (MeOH) (Lit: 70 C., aqueous MeOH obtained by Khan, M A; Lynch, B M; Hung, Y-Y; Can. J. Chem. 1963, 41, 1540-1547); 1H NMR/CDCl3 (250 MHz): δ 7.88 (dd, 1H, 3JHH=2.5 Hz, 4JHH=0.5 Hz, H5), 7.72 (dd, 1H, 3JHH=1.7 Hz, 4JHH=0.5 Hz, H3), 7.52-7.62 (m, 4H, H6,7,8,9), 6.46 (dd, 1H, 3JHH=1.7 Hz, 3JHH=2.5 Hz, H4); 13C NMR/CDCl3: δ 141.41 (C3), 139.21 (C1), 132.46 (C6 and C7), 126.64 (C5), 120.59 (C8 and C9), 119.62 (C2), 108.83 (C4); GC/MS: Rt=16.90 min, M/Z=222 and 224, purity=100%; Rf=0.21 (eluent: hexane/dichloromethane, 50/50). | |
8.9 g | With 2-Picolinic acid; potassium phosphate; copper(l) iodide; In dimethyl sulfoxide; at 160℃; for 24h; | 11.8 grams (g) (50 millimoles (mmol)) of 1,4-dibromobenzene, 3.4 g (50 mmol) of pyrazole, 23 g (100 mmol) of tripotassium phosphate, 1.83 g (10 mmol) of iodocopper, and 1.17 g (10 mmol) of picolinic acid were added to a reaction vessel. The mixture was suspended in 100 milliliters (mL) of dimethylsulfoxide. The mixture was stirred at 160 C. for 24 hours. Once the reaction was complete, the mixture was allowed to cool to room temperature. Then, 300 mL of distilled water was added thereto, and an organic layer was extracted using ethyl acetate. The extracted organic layer was washed with saturated sodium chloride aqueous solution, followed by drying over sodium sulfate. The residue from which the solvent was removed was separated by column chromatography to thereby obtain 8.9 g (40 mmol) of Intermediate 1-A. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine; In acetonitrile; at 82℃;Inert atmosphere; | Compound 74.1. l-(4-Bromophenyl)-lH-pyrazole. Into a 100-mL round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a mixture of 1 -bromo-4-iodobenzene (2.82 g, 9.97 mmol), lH-pyrazole (680 mg, 9.99 mmol), Cul (380 mg, 2.00 mmol), DMEDA (430 μ,, 4.00 mmol, 0.40 equiv), Cs2C03 (6.52 g, 20.00 mmol) an CH3CN (40 mL). The resulting mixture was stirred overnight at 82 C. After cooling to ambient temperature, the solids were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1 : 12) as the eluent to yield the title compo |
94% | With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine; In acetonitrile; at 82℃;Inert atmosphere; | Compound 74.1. l-(4-Bromophenyl)-lH-pyrazole. Into a 100-mL round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a mixture of 1 -bromo-4-iodobenzene (2.82 g, 9.97 mmol), lH-pyrazole (680 mg, 9.99 mmol), Cul (380 mg, 2.00 mmol), DMEDA (430 μ, 4.00 mmol, 0.40 equiv), Cs2C03 (6.52 g, 20.00 mmol) an CH3CN (40 mL). The resulting mixture was stirred overnight at 82 C. After cooling to ambient temperature, the solids were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1 : 12) as the eluent to yield the title compound as a white solid (2.1 g, 94%). |
78% | With (N,N'-bis(salicylidenate)cyclohexane-1,2-diamine)copper(II); sodium hydroxide; In dimethyl sulfoxide; at 100℃; for 12h;Sealed tube; | General procedure: Complex 2 (0.05 mmol) was added to a 5 mL of a sealed tube containing the aryl iodide or bromide (0.5 mmol), 1H-pyrazole (0.75 mmol), NaOH (1 mmol), and DMSO (1 mL). The mixture was stirred at 100 C for 12 h. After being cooled to room temperature, the mixture was quenched with 10 mL H2O and extracted with EtOAc(3 × 20 mL). The combined EtOAc extracts were dried with anhydrous Na2SO4, filtered and the solvent was removed under reduced pressure.The residue was purified by flash column chromatography on silicagel with PE/EtOAc (from 10:1 to 5:1) as the eluent to afford the pure products. All N-aryl pyrazoles reported here are known products and were characterised by 1H NMR, and GC-MS. |
73% | With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine; In acetonitrile; at 80℃; for 16h; | CuI (27 mg, 0.141 mmol, 20 mol %) was added to a degassed solution of iodine derivative 110 (200 mg, 0.707 mmol, 1.0 eq.), of amine 111 (50.5 mg, 0.742 mmol, 1.05 eq.), N,N′-dimethylethylenediamine (0.026 ml, 0.282 mmol, 20% mol) and CsCO3 (459 mg, 1.41 mmol, 2.0 eq.) in 3.0 ml of CH3CN. The mixture was stirred at 80 C. for 16 h under argon. Then the mixture was cooled and filtered through Celite. The filtrate is evaporated under reduced pressure before being purified by flash column chromatography on silica gel with eluent (ethyl acetate/petroleum ether=25/75) to obtain 115 mg of the bromine 112 in the form of a colorless oil with a yield of 73% yield. 1H NMR (250 MHz, CDCl3, 20 C.) δ 7.86 (m, 1H), 7.69 (m, 1H), 7.55 (m, 4H), 6.45 (m, 1H). Numro CAS Number: 13788-92-6. |
67% | With copper diacetate; sodium hydroxide; 3-(diphenylphosphino)propionic acid; In 1,4-dioxane; at 100℃; for 24h;Sealed tube; | General procedure: Cu(OAc)2 (0.03mmol), L2 (0.06mmol), aryl idione or bromide (0.5mmol), 1H-pyrazole (0.75mmol), NaOH (1mmol), and 1,4-dioxane (1mL) was added into a 5mL tube, then sealed. The mixture was stirred at 100C for certain time. After cooling to room temperature, the mixture was quenched with 10mL H2O and extracted with EtOAc (3×20mL). The combined EtOAc extracts were dried with anhydrous Na2SO4 and filtrated and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel with PE/EtOAc, as the eluent, to afford the desired products. |
50% | With copper(l) iodide; manganese(II) fluoride; (1R,2R)-1,2-diaminocyclohexane; potassium hydroxide; In water; at 60℃; for 24h; | General procedure: The N-nucleophile (1.47 mmol), CuI (Sigma-Aldrich, 99.999% purity, 0.147 mmol), MnF2 (Sigma-Aldrich, 98% purity, 0.441 mmol), KOH (2.94 mmol), the aryl halide (2.21 mmol), trans-1,2-diaminocyclohexane (0.294 mmol) and water (0.75 mL) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 60C for 24 h. After cooling to room temperature, the mixture was diluted with dichloromethane and filtered through a pad of Celite. The combined organic extracts were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of known products was confirmed by 1H and 13C NMR spectroscopic analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With caesium carbonate;copper(I) oxide; trans-N,N'-bis(pyridin-2-ylmethylene)cyclohexane-1,2-diamine; In acetonitrile; at 82℃; for 48h;Conversion of starting material; | Example 1.9 [0564] Preparation of 1H, ?H-1,1?-p-phenylene-bis-pyrazole Example 1.8 was repeated, replacing the 1-(4?-bromophenyl)-1H-imidazole with 1-(4?-bromophenyl)-1H-pyrazole (2.4 mmoles, 535 mg). [0565] Pale yellow crystals were obtained which could be rendered colourless by re-crystallisation from chloroform. [0566] The degree of transformation and isolated yield were 100%. [0567] The compound obtained had the following formula: [CHEMMOL-00048] [0568] The characteristics were as follows: [0569] M Pt: 180 C. (CHCl3): (Lit: 182 C., CHCl3 obtained by Kauffmann, T; Lexy, H., Chem. Ber. 1980, 113, 2749-2754); [0570] 1H NMR/CDCl3 (250 MHz): ? 7.95 (dd, 1H, 3JHH=2.5 HZ, 4JHH=0.6 Hz, H5), 7.79 (s, 2H, H2,6), 7.74 (dd, 1H, 3JHH=1.6 Hz, 4JHH=0.6 Hz, H3), 6.49 (dd, 1H, 3JHH=1.6 Hz,3JHH=2.5 Hz, H4); [0571] 13C NMR/CDCl3: ? 141.31 (C3), 138.41 (C1), 126.74 (C5), 120.04 (C2 and C6), 107.90 (C4); [0572] GC/MS: Rt=21.28 min, M/Z=210, purity=98%; [0573] Rf=0.38 (eluent: dichloromethane/ethyl acetate, 90/10). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.73 g (37%) | Pd(Ph3P)2Cl2; copper(I) iodide; In triethanolamine; water; ethyl acetate; | Step A 3-[4-(1H-pyrazol-1-yl)phenyl]-2-propyn-1-ol A mixture of <strong>[13788-92-6]1-(4-bromophenyl)-1H-pyrazole</strong> (prepared as described in Bull. Soc. Chim. Fr. 1966, 2832) (2.24 g, 10.04 mmol), Pd(Ph3P)2Cl2 (180 mg, 0.26 mmol), and copper(I) iodide (95 mg, 0.50 mmol) in TEA (20 mL) was stirred for 5 min, propargyl alcohol (0.70 mL, 12.02 mmol) was added, and the mixture was heated to 80 C. for 48 h. The volatiles were evaporated, ethyl acetate (50 mL) and water (50 mL) were added to the residue, and the mixture was filtered through a pad of Celite. The organic layer from the filtrate was washed with brine (50 mL), dried (Na2SO4), and concentrated. Purification by chromatography (SiO2, 3:2 hexane/ethyl acetate) yielded 0.73 g (37%) of the title compound as a brown solid. MS 199 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | tetrakis(triphenylphosphine) palladium(0); In toluene; at 100℃; for 2h; | A. l-(4-(Trimethylstannyl)phenyl)-lH-pyrazole. A solution of 1 -(4- bromophenyl)-lH-pyrazole (1.0 g, 4.48 mmol), hexamethylditin (1.08 mL, 4.93 mmol), tetrakis(triphenylphosphine)palladium(0) (0.508 g, 0.06 mmol) in toluene (15 mL) was heated at 100 C for 2 h. Upon completion of the reaction, toluene was removed under reduced pressure, and the residue was purified by Biotage chromatography (0-40% ethyl acetate in hexanes) to afford the desired product (1.20 g, 87%). MS (ESI) m/z 309.3[M+l]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 100℃;Inert atmosphere; | 1-(4-bromophenyl)-1 H-pyrazole (0.34 g, 1.5 mmol), bis(pinacolato)diborane (0.53 g, 2.1 mmol) and potassium acetate (446mg,4.5mmol) were combined in a 4 dram vial in 10ml_ dioxane. The reaction mixture was bubbled with nitrogen for 10 minutes then Pd(dppf)CI2 (1 10mg, 0.15mmol) was added. The reaction was heated at 100C overnight. The reaction was diluted with 20ml_ of EtOAc and 20ml_ of 1 : 1 saturated sodium bicarbonate / water. The organic layer was isolated and the aqueous layer was back-extracted once with 10ml_ of EtOAc. The organic layers were combined, dried over solid magnesium sulfate, filtered and concentrated. The crude material was puified by eluting the material through a short pad of silica gel with EtOAc to provide a dark solid (0.42 g, 100 %). MS (LCMS) m/z 271.4 (M+1 ). 1H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.35 (s, 12 H) 6.46 (dd, J=2.54, 1.76 Hz, 1 H) 7.68 - 7.72 (m, 2 H) 7.72 (d, J=1.76 Hz, 1 H) 7.85 - 7.90 (m, 2 H) 7.96 (d, J=1.76 Hz, 1 H). |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 120℃; for 3h;Inert atmosphere; | 0.26 g (1.16 mmol) of 1- (4-bromophenyl) -1H-pyrazole was weighed,0.34 g (1.38 mmol) of diphenylolate borate,Potassium acetate 0.34 g (3.48 mmol) andPd (dppf) Cl2 0.06 g (0.08 mmol) in a 100 mL eggplant type flask, Adding dioxane 12mL, nitrogen protection, heating at 120 reflux 3h,To obtain the product containing the product1- [4- (4,4,5,5-tetramethyl-1, 3,2-Dioxaborolan-2-yl)Phenyl] -1H-Pyrazole reaction system,Cooled to room temperature,To this system was added 0.30 g (0.95 mmol) of (S) -N1- (5-bromo-2-pyrazinyl) -1,2-tetrahydropyrformamide,0.78 g (2.85 mmol) of potassium carbonate, 0.05 g (0.07 mmol) of Pd (dppf) Cl2 and 3 mL of water, protected with nitrogen and heated at 120 C for 3 hours,Cooling to room temperature, steaming to remove the solvent, silica gel column chromatography purification three times,Eluent (V / V): chloroform / methanol = 20/1 to give 0.12 g of a white solid, yield: 33.48%, mp: 235-238 C. | |
13.2 g | With bis-triphenylphosphine-palladium(II) chloride; potassium acetate; In toluene; at 110℃;Inert atmosphere; | D);To a solution of <strong>[13788-92-6]1-(4-bromophenyl)-1H-pyrazole</strong> (12.8 g), bis(pinacolato)diboron (29.0 g), potassium acetate (16.8 g) in toluene (300 mL) was added (Ph3P)2PdCl2 (4.01 g), and the mixture was stirred under an argon atmosphere at 110C overnight. An insoluble material was removed by filtration, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (13.2 g, containing bis(pinacolato)diboron). MS (ESI+): [M+H]+271.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12% | With trichlorophosphate; In N,N-dimethyl-formamide; at 0 - 110℃; for 3h; | 50 mL of DMF was cooled to 0C, and POCl3 was added thereto. The mixture was stirred for 15 minutes. 1-(4-bromophenyl)pyrazole (3.45 g, 14.7 mmol) obtained in Step A was slowly added thereto, and the mixure was stirred at110C for 3 hours. After cooling to room temperature, sodium bicarbonate aqueous solution was added thereto, and themixture was stirred for 30 minutes. The reaction solution was extracted with Et2O and purified by column chromatographyto obtain the title compound (0.45 g, 12 %).1H-NMR (CDCl3) δ 9.97 (1H, s), 8.42 (1H, s), 8.17 (1H, s), 7.62 (4H, m) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With Potassium phosphate; In N,N-dimethyl-formamide; at 150℃; for 27h; | 1H-pyrazole (1.0 g, 14.7 mmol) and 4-bromofluorobenzene (5.14 g, 29.4 mmol) were dissolved in 80 mL ofDMF. Potassium phosphate (15.6 g, 73.5 mmol) was added thereto, and the mixture was stirred at 150C for 27 hours.After addition of 150 mL of water, the reaction solution was extracted with Et2O to obtain the title compound (3.45 g, 99 %).1H-NMR (CDCl3) δ 7.90 (1H, m), 7.72 (1H, m), 7.58 (4H, m), 6.48 (1H, m) |
13 g | With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 20 - 130℃; for 5.5h;Cooling with ice; | To a solution of 1-bromo-4-fluorobenzene (10.0 g) and 1H-pyrazole (3.89 g) in DMF (100 mL) was added under ice-cooling sodium hydride (2.29 g, 60%, oily), and the mixture was stirred at room temperature for 30 min and further at 130C for 5 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure to give the title compound (13.0 g). MS (ESI+): [M+H]+222.8. |
With potassium phosphate; In 1-methyl-pyrrolidin-2-one; at 200℃; for 2h;Sealed tube; | A mixture of lH-pyrazole (680 mg, 10 mmol), l-bromo-4-fluorobenzene (450A, 3.50 g, 20 mmol), and K3PO4 (6.37 g, 30 mmol) in NMP (20 mL) was heated in a sealed tube at 200 C for 2 hours. The mixture was cooled down to room temperature, quenched with water (100 mL), and extracted with ethyl acetate (100 mL x 3). The combined organic layers was washed with brine (100 mL), dried over anhydrous sodium sulfate, concentrated, and purified with column chromatography on silica gel (ethyl acetate in petroleum ether, 10%, v/v) to furnish Compound 450B. LC-MS (ESI) m/z: 223 [M+H]+. |
With potassium phosphate; In 1-methyl-pyrrolidin-2-one; at 200℃; for 2h;Sealed tube; | A mixture of 1H-pyrazole (680 mg, 10 mmol), 1-bromo-4-fluorobenzene (450A, 3.50 g, 20 mmol), and K3PO4 (6.37 g, 30 mmol) in NMP (20 mL) was heated in a sealed tube at 200 C for 2 hours. The mixture was cooled down to room temperature, quenched with water (100 mL), and extracted with ethyl acetate (100 mL x 3). The combined organic layers was washed with brine (100 mL), dried over anhydrous sodium sulfate, concentrated, and purified with column chromatography on silica gel (ethyl acetate in petroleum ether, 10%, v/v) to furnish Compound 450B. LC-MS (ESI) m/z: 223 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | DMF (3 mL) was cooled to 0 C and POC13 (5.01 mL, 53.8 mmol) was then added dropwise. Reaction stirred at 0 C for 5 minutes. <strong>[13788-92-6]1-(4-bromophenyl)-1H-pyrazole</strong> (3 g, 13.4 mmol) dissolved in DMF (7 mL) was then added, and the reaction was heated to 100 C for 8 h. Reaction mixture was cooled to rt and poured into ice. Brown solid was collected by filtration, washed with water then dissolved in DCM, washed with brine,dried with Na2SO4, filtered and evaporated to yield the aldehyde (2.78 g, 82%) as a brown solid. ‘H NMR (500MHz, DMSO-d6) ö 9.93 (s, 1H), 9.27 (s, 1H), 8.30 (s, 1H), 7.96-7.87 (m, 2H), 7.80-7.73 (m, 2H). |
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