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Structure of 4-Chlorobenzyl bromide
CAS No.: 622-95-7
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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.
4.5
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Quinolone-3-amidoalkanol: A New Class of Potent and Broad-Spectrum Antimicrobial Agent
Dube, Phelelisiwe S. ; Angula, Klaudia T. ; Legoabe, Lesetja J. ; Jordaan, Audrey ; Boitz Zarella, Jan M. ; Warner, Digby F. , et al.
Abstract: Herein, we describe 39 novel quinolone compounds bearing a hydrophilic amine chain and varied substituted benzyloxy units. These compounds demonstrate broad-spectrum activities against acid-fast bacterium, Gram-pos. and -neg. bacteria, fungi, and leishmania parasite. Compound 30 maintained antitubercular activity against moxifloxacin-, isoniazid-, and rifampicin-resistant Mycobacterium tuberculosis, while 37 exhibited low micromolar activities (<1 μg/mL) against World Health Organization (WHO) critical pathogens: Cryptococcus neoformans, Acinetobacter baumannii, and Pseudomonas aeruginosa. Compounds in this study are metabolically robust, demonstrating % remnant of >98% after 30 min in the presence of human, rat, and mouse liver microsomes. Several compounds thus reported here are promising leads for the treatment of diseases caused by infectious agents.
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Highly compressible glass-like supramolecular polymer networks
Zehuan Huang ; Xiaoyi Chen ; Stephen J. K. O’Neill ; Guanglu Wu ; Daniel J. Whitaker ; Jiaxuan Li , et al.
Abstract: Supramolecular polymer networks are non-covalently crosslinked soft materials that exhibit unique mechanical features such as self-healing, high toughness and stretchability. Previous studies have focused on optimizing such properties using fast-dissociative crosslinks (that is, for an aqueous system, dissociation rate constant kd > 10 s−1). Herein, we describe non-covalent crosslinkers with slow, tuneable dissociation kinetics (kd < 1 s−1) that enable high compressibility to supramolecular polymer networks. The resultant glass-like supramolecular networks have compressive strengths up to 100 MPa with no fracture, even when compressed at 93% strain over 12 cycles of compression and relaxation. Notably, these networks show a fast, room-temperature self-recovery (< 120 s), which may be useful for the design of high-performance soft materials. Retarding the dissociation kinetics of non-covalent crosslinks through structural control enables access of such glass-like supramolecular materials, holding substantial promise in applications including soft robotics, tissue engineering and wearable bioelectronics.
Show More >
Purchased from AmBeed: 2243-54-1 ; 17201-43-3 ; 589-15-1 ; 106797-53-9 ; 622-95-7 ; 16004-15-2 ; 7646-67-5
Show More >
CAS No. : | 622-95-7 |
Formula : | C7H6BrCl |
M.W : | 205.48 |
SMILES Code : | ClC1=CC=C(CBr)C=C1 |
MDL No. : | MFCD00040714 |
InChI Key : | KQNBRMUBPRGXSL-UHFFFAOYSA-N |
Pubchem ID : | 69329 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 1759 |
Packing Group: | Ⅱ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 44.29 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.32 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.35 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.08 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.68 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.49 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.18 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.65 |
Solubility | 0.0458 mg/ml ; 0.000223 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.03 |
Solubility | 0.193 mg/ml ; 0.000939 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.28 |
Solubility | 0.0109 mg/ml ; 0.000053 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.17 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.52 |
* 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 |
---|---|---|
4-(4-Chloro-benzyl)-5-oxo-[l,4]diazepane-l-carboxylic acid t-butyl ester5-Oxo-[l,4]diazepane-l-carboxylic acid t-butyl ester (70 mg, 0.33 mmol) was added to a solution of KHMDS (91 mg, 0.46 mmol) in dry THF (1.6 ml) at app. -70 0C. After stirring <n="39"/>for 15 min the/?-chlorobenzyl bromide (74 mg, 0.36 mmol) was added to the reaction mixture. The reaction was quenched after 6 h at -75 0C by addition OfH2O and diluted with CH2Cl2. The organic phase was washed with H2O and filtered through an Extrelut tube.(R)., which was rinsed with CH2Cl2. The resulting organic phase was evaporated and purified by flash chromatography (SiO2, CH2Cl2-EtOAc) to give 50 mg of the subtitled compound as a semisolid.1R NMR (CD3OD) delta 7.31 (m, 4H), 4.58 (s, 2H), 3.59 (m, 2H), 3.44-3.50 (m, 4H), 2.75 (m,2H), 1.45 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With sodium hydride; In dimethyl sulfoxide; mineral oil; at 20℃; for 0.25h;Inert atmosphere; | According to Scheme 4 Step 1: To a solution of Azathymine (300 mg, 2.36 mmol) and 4-chlorobenzyl bromide (485 mg, 2.36 mmol) in DMSO (10 mL) was added portionwise NaH (55%) (103 mg, 2.36 mmol) at room temperature under nitrogen atmosphere. The mixture was stirred for 15 min at room temperature. Ethyl Acetate was then added (150 mL) and the organic layer was extracted thrice with water (100 mL). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure to afford a yellow solid. The crude solid was purified by flash chromatography with silica gel using CH2Cl2/MeOH 98/2 as eluant to afford 4-(4-chlorobenzyl)-<strong>[932-53-6]6-methyl-1,2,4-triazine-3,5(2H,4H)-dione</strong> 8(A) (500 mg, 84%) as a white solid.LC1: Rt=3.66MS m/z (ES) [M-H]-=249 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A mixture of <strong>[93247-78-0]methyl indole-7-carboxylate</strong> (6.0 g) and DMF (60 mL) was ice-cooled, and potassium tert-butoxide (5.38 g) was added thereto, followed by stirring at the same temperature for 30 minutes. Then, 4-chlorobenzylbromide (7.39 g) was added thereto, followed by stirring at room temperature for 3 hours. The reaction mixture was ice-cooled, and water (60 mL) was added thereto, followed by extraction with ethyl acetate (80 mL). The organic layer was washed with 1 M hydrochloric acid, a saturated sodium bicarbonate solution, and saturated saline in this order, dried over magnesium sulfate, and then concentrated under reduced pressure. The residue was left to stand for 3 days for solidification, and washed with hexane-ethyl acetate (8:1, 18 mL) to obtain methyl 1-(4-chlorobenzyl)-1H-indole-7-carboxylate (4.94 g) as a pale yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 16h; | 0.800 g of <strong>[71486-53-8]methyl 4-oxopiperidine-3-carboxylate hydrochloride</strong> (4.134 mmol), 1.44 mL (8.268 mmol) of diisopropylethylamine and 0.852 g (4.134 mmol) of 4-chloro-benzyl bromide were stirred at room temperature in 16.0 mL of anhydrous CH2C12.The reaction was monitored by HPLC and UPLC-MS. After 16 h at room temperature, brine was added to the reaction mixture.The organic phase was separated, dried over Na2SO4 and concentrated in vacuo to give pure methyl methyl 1-(4-chlorobenzyl)-4-oxopiperidine-3-carboxylate (1.164 g, 4.133 mmol, quantitative yield).The product was used for the next step without further manipulation. MS(ESI+): 282.1. |
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 16h; | 0.800 g of <strong>[71486-53-8]methyl 4-oxopiperidine-3-carboxylate hydrochloride</strong> (4.134 mmol), 1.44 mL (8.268 mmol) of diisopropylethylamine and 0.852 g (4.134 mmol) of 4-chloro-benzyl bromide were stirred at room temperature in 16.0 mL of anhydrous CH2CI2. The reaction was monitored by HPLC and UPLC-MS. After 16 h at room temperature, brine was added to the reaction mixture. The organic phase was separated, dried over Na2S04 and concentrated in vacuo to give pure methyl methyl l-(4-chlorobenzyl)-4- oxopiperidine-3-carboxylate (1.164 g, 4.133 mmol, quantitative yield). The product was used for the next step without further manipulation. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With potassium carbonate; In acetonitrile; for 7h;Reflux; | Step 1 Potassium carbonate (0.7 g, 5.1 mmol) and 4-chlorobenzyl bromide (0.76 g, 3.7 mmol) were added to mixture of 7-bromo-3-(ethoxycarbonyl)quinolin-4(1H)-one (1.0 g, 3.4 mmol) and acetonitrile (20 mL), and stirred under heating at reflux for 7 hours. The insoluble matter was removed by filtering, and the filtrate was washed by ethyl acetate and concentrated in vacuo. The resulting solid was washed by water and hexane to give 7-bromo-1-(4-chlorobenzyl)-3-(ethoxycarbonyl)quinolin-4(1H)-one (1.11 g, yield: 78%) as colorless solid. 1H-NMR (delta ppm TMS/DMSO-d6): 1.29 (3H, t, J=6.0 Hz), 4.24 (2H, q, J=6.0 Hz), 5.69 (2H, s), 7.28 (2H, d, J=8.0 Hz), 7.44 (2H, d, J=8.0 Hz), 7.61 (1H, d, J=8.0 Hz), 7.85 (1H, s), 8.14 (1H, d, J=8.0 Hz), 8.89 (1H, s). |
61% | With potassium carbonate; In acetonitrile; at 100℃; for 5h; | [Example 44] Preparation of 1-(4-chlorobenzyl)-7-(phenylamino)-3-(ethoxycarbonyl)quinoline-4(1H)-one (I-148) To a mixture of 7-bromo-3-(ethoxycarbonyl)quinoline-4(1H)-one (250 mg, 0.844 mmol) and acetonitrile (5 mL) were added potassium carbonate (175 mg, 1.27 mmol) and 4-chlorobenzylbromide (208 mg, 1.01 mmol), and the resulting mixture was stirred at 100C for 5 hours. The insoluble were removed by filtration and washed by ethyl acetate. The mother liquor was concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give 7-bromo-1-(4-chlorobenzyl)-3-(ethoxycarbonyl)quinoline-4(1H)-one (216 mg, Yield: 61%) as colorless solid. 1H-NMR (delta ppm TMS/DMSO-d6): 1.29 (3H, t, J=6.0 Hz), 4.24 (2H, q, J=6.0 Hz), 5.69 (2H, s), 7.28 (2H, d, J=8.0 Hz), 7.44 (2H, d, J=8.0 Hz), 7.61 (1H, d, J=8.0 Hz), 7.85 (1H, s), 8.14 (1H, d, J=8.0 Hz), 8.89 (1H, s). |
61% | With potassium carbonate; In acetonitrile; at 100℃; for 5h; | EXAMPLE 44 Preparation of 1-(4-chlorobenzyl)-7-(phenylamino)-3-(ethoxycarbonyl)quinoline-4(1H)-one (I-148) To a mixture of 7-promo-3-(ethoxycarbonyl)quinoline-4(1H)-one (250 mg, 0.844 mmol) and acetonitrile (5 mL) were added potassium carbonate (175 mg, 1.27 mmol) and 4-chlorobenzylbromide (208 mg, 1.01 mmol), and the resulting mixture was stirred at 100 C. for 5 hours. The insoluble were removed by filtration and washed by ethyl acetate. The mother liquor was concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give 7-bromo-1-(4-chlorobenzyl)-3-(ethoxycarbonyl)quinoline-4(1H)-one (216 mg, Yield: 61%) as colorless solid. 1H-NMR (delta ppm TMS/DMSO-d6): 1.29 (3H, t, J=6.0 Hz), 4.24 (2H, q, J=6.0 Hz), 5.69 (2H, s), 7.28 (2H, d, J=8.0 Hz), 7.44 (2H, d, J=8.0 Hz), 7.61 (1H, d, J=8.0 Hz), 7.85 (1H, s), 8.14 (1H, d, J=8.0 Hz), 8.89 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
500 mg | With silver carbonate; In tetrahydrofuran; for 2h;Reflux; | B) 6- ( (4-Chlorobenzyl) oxy) pyrimidin-4 (3H) -one. To a stirred solution of pyrimidine-4 , 6-diol (2.5 g) in THF (25 ml) was added silver carbonate (15.3 g) at room temperature followed by dropwise addition of 4-chlorobenzyl bromide (4.58 g) , and the resultant mixture was heated at reflux for 2 h. The reaction mixture was then cooled to room temperature, filtered through Celite, and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (MeOH/DCM) to give the title compound (500 mg) as a white solid. MS (ESI+) : [M+H]+ 237.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In acetonitrile;Irradiation; | General procedure: A mixture of 1,2-Diaminobenzene 1 or 2-Mercaptoaniline 4(1 mmol), benzyl bromides (1 mmol) 2 and 4 % Cu:ZnS NPs (10 mol %)in 10 ml of CH3CN were irradiated in visible light (100W OSRAMTungsten Lamp, EFP 64627 HLX) with continuous stirring for the appropriatetime. Catalyst was separated by centrifugation after thecompletion of reaction. Evaporation of the above solution gave thecrude product which was purified using crystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0℃; for 1h;Inert atmosphere; | Synthesis of 2-chloro-8-(4-chlorobenzyl)-7 , 8-dihydro-6H-pyrimido [5, 4-b] [I, 4] oxazine [0450] To a stirred solution of 2-chloro-7, 8-dihydro-6H-pyrimido [5, 4-b] [1, 4] oxazine (150 mg, 0.87 mmol) in DMF (3 mL) under argon atmosphere were added sodium hydride (40 mg, 1.75 mmol) and l-(bromomethyl)-4-chlorobenzene (215 mg, 1.05 mmol) at 0 C. The reaction mixture was stirred for 1 h at 0 C. After consumption of the starting materials (monitored by TLC), the reaction was diluted with water (50 mL) and extracted with EtOAc (2 x 50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was washed with n-pentane (2 x 5 mL) to afford 2- chloro-8-(4-chlorobenzyl)-7, 8-dihydro-6H-pyrimido [5, 4-b] [1, 4] oxazine (190 mg, 73%) as an off-white solid. 1H-NMR (DMSO-<, 500 MHz): delta 7.73 (s, 1H), 7.42 (d, 2H), 7.33 (d, 2H), 4.78 (s, 2H), 4.20-4.18 (m, 2H), 3.52-3.49 (m, 2H); LCMS: 295.8 (M+); (column; X- Select CSH C-18 (50 3.0 mm, 3.5 mupiiota); RT 3.81 min. 0.05% Aq TFA: ACN; 0.80 mL/min); UPLC (purity): 91.4%; (column; Acquity UPLC BEH C-18 2.1 X 50 mm, 1.7 mupiiota); RT 2.52 min. ACN: 0.025% TFA (Aq); 0.50 mL/min; TLC: 30% EtOAc:hexanes (R 0.6). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17.1% | 4-(Benzo[d][1,3]dioxol-5-yl)thiazol-2-amine(2) (1.00 g, 4.54 mmol) and NaH (0.164 g, 6.82 mmol) to THF (15 ml) todissolved and then allowed to react at room temperature for 1 hour under a nitrogen stream. After dropwise addition of 4chlorobenzylbromide (1.40 g, 6.82 mmol) slowly at room temperature and reacted for 10 minutes. After the reaction wasfinished, it was concentrated under reduced pressure and extracted three times into a saturated solution of NaHCO3 isdissolved in ethyl acetate. The ethyl acetate layer was separated and dried with anhydrous Na2SO4, then purified by columnchromatography (Ethyl acetate: Hexane = 1: 5) to give the compound 1g to give. Yield 17.1% | |
17% | General procedure: A solution of <strong>[185613-91-6]4-(benzo[d][1,3]dioxol-5-yl)thiazol-2-amine</strong> (1.0 equiv) and NaH (1.5 equiv) in THF was stirred at room temperature. After 1 h, benzyl bromide (1.5 equiv) was added and stirring was continued for 10 more min. The reaction progress was monitored by TLC. After completion of the reaction, quenched with saturated NH4Cl solution and extracted with EtOAc, the organic layer was dried over MgSO4, filtered, concentrated invacuo. The residue was purified by silica gel column chromatography (16% EtOAc/hexanes) to afford desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With potassium carbonate; In N,N-dimethyl-formamide; at 60℃;Inert atmosphere; | General procedure: To a solution of the corresponding N-Boc-aminophenol (1 mmol) in DMF (2 mL), K2CO3 (207 mg,1.5 mmol) and the required benzyl bromide (1 mmol) were added. The mixture was stirred at 60 Cuntil no starting material was observed by TLC. A saturated aqueous solution of ammonium chloridewas added (5 mL) and the resulting mixture extracted with EtOAc (10 mL ×3), the organic extractswashed with brine (20 mL) and dried over MgSO4. The crude product was purified by FC eluting withhexane/EtOAc (95:5 ? 9:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | (<strong>[5932-27-4]ethyl 1H-pyrazole-3-carboxylate</strong>, 1.050 g, 7.49 mmol) was dissolved in ACN (20 mL)Cs2CO3 (2.4 g, 1.0 eq) was added. After stirring for 30 minutes, 4-chlorobenzyl bromide (1.7 g, 1.1 eq) was further added, and the mixture was stirred at room temperature for 5 hours.The solvent was evaporated off, extracted with MC, treated with MgSO4, filtered, and silica-columned with EA: Hex (1: 3) to give starting material 1 (836 mg, 42percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
162 mg | With caesium carbonate; In acetonitrile; at 20℃; for 2h; | To a solution of <strong>[35344-95-7]1H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong></strong> (70 mg, 728 mumol) in MeCN (5 mL) was added 1-(bromomethyl)-4-chlorobenzene (149 mg, 728 mumol) and cesium carbonate (472 mg, 1.45 mmol). The mixture was stirred at r.t. for 2h. The mixture was concentrated, diluted with EA and water. The organic phase was washed with brine (10 mL x 2), dried over Na2SO4and concentrated to give 1-(4-chlorobenzyl)-1H- <strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> (162 mg, 101 percent) as a white solid, which was used in the next step without further purification |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34.2% | With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 16h; | Compound cyanoimidazole (1.00 g, 10.74 mmol), N,N-dimethylformamide (20 ml), 1-(bromomethyl)-4-chlorobenzene (2.65 g, 12.89 mmol) and cesium carbonate (7.00 g, 21.48 mmol) was sequentially added to a dry 100 ml one-neck flask at room temperature, and heated to 100°C for 16 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, poured into 200 ml of water and extracted with ethyl acetate (80 ml 3 2). The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified through a chromatography column (petroleum ether: ethyl acetate = 1:1) give a product 1-(4-chlorobenzyl)-<strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong> (0.80 g, yellow oil), yield 34.2percent. 1H-NMR(CDCl3, 400 MHz):8.22(s,1H), 8.04 (s, 1H), 7.46-7.44(d,J =8.4Hz, 2H), 7.35-7.33(d,J=8.0Hz, 2H), 5.29 (s,2H). |
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