Structure of 4-Chlorophenylboronic acid
CAS No.: 1679-18-1
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CAS No. : | 1679-18-1 |
Formula : | C6H6BClO2 |
M.W : | 156.38 |
SMILES Code : | ClC1=CC=C(B(O)O)C=C1 |
MDL No. : | MFCD00039137 |
InChI Key : | CAYQIZIAYYNFCS-UHFFFAOYSA-N |
Pubchem ID : | 74299 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 41.28 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.45 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.02 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.08 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.45 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.1 |
Solubility | 1.24 mg/ml ; 0.00792 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.91 |
Solubility | 1.94 mg/ml ; 0.0124 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.89 |
Solubility | 2.01 mg/ml ; 0.0129 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
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) |
No |
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 |
-6.22 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) |
1.68 |
* 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 |
---|---|---|
85% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; toluene for 24 h; Inert atmosphere; Reflux | Round bottom flask was charged with 9-Phenyl-9H-carbazole-3-boronic acid 15g (52.25mmol), 4-chloro-Phenylboronicacid8.98g (57.47mmol) and the mixture of toluene (174ml) and the mixture was then dissolved in 21.66g of potassium carbonate (156.74 mmol) was added to a stirred aqueous solution of dissolved 87ml. Followed by adding thereto tetrakis triphenylphosphine palladium 1.20g (1.04mmol) was stirred and refluxed for 24 hours under a nitrogen atmosphere. After the end of the reaction the extract was concentrated to dryness and extracted with ethyl acetate and filtered through a magnesium sulfate, and the filtrate under reduced pressure. The product n- hexane / dichloromethane (6: 4 by volume) was purified by a silica gel column chromatography to give the intermediate (I) as 16.13g (85percent yield). |
85% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; toluene for 24 h; Inert atmosphere; Reflux | Round bottom flask was charged with 9-Phenyl-9H-carbazole-3-boronic acid 15g (52.25mmol), 4-chloro-Phenylboronicacid 8.98g dissolved in an aqueous solution of potassium carbonate 21.66g (156.74mmol) was dissolved was added to (57.47mmol) in toluene (174ml) into theIt was added to 87ml and stirred. Here tetrakistriphenylphosphine palladium was added to 1.20g (1.04mmol) of nitrogen atmosphere It was stirred under reflux for 24 hours under a group. After completion of the reaction, magnesium sulfate, the extract was then extracted with ethyl acetateIt was dried, filtered and concentrated under reduced pressure to the filtrate. Silica gel with: a product n- hexane / dichloromethane (volume ratio 4 6)The desired compound was purified by column chromatography of the intermediate (I) to give a 16.13g (85percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; at 20 - 100℃; for 5h; | C. Preparation of 4-chloro-6-(4-chlorophenyl)-5-phenylpyrimidine To a mixture of <strong>[3974-16-1]4,6-dichloro-5-phenylpyrimidine</strong> (675 mg, 3.0 mmol), 4-chlorophenylboronic acid (704 mg, 4.5 mmol) and tetrakis(triphenylphosphine)palladium (173 mg, 0.15 mmol) in toluene (10 mL) at room temperature under argon was added aqueous Na2CO3 solution (2 M, 3 mL, 6 mmol). The resulting reaction mixture was stirred at 100 C. under argon for 5 h, after which time analysis by HPLC/MS indicated that the the reaction was complete. After cooling the reaction mixture to room temperature, water (15 mL) was added. The resulting mixture was extracted with EtOAc (2*25 mL). The combined organic layers were washed with saturated aqueous NaCl, then dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with ethyl acetate-hexanes to obtain 571 mg of the title compound as a white solid. HPLC/MS: retention time=3.85 min, [M+H]30 =301. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; water; at 80℃; for 18.25h; | Step B: [4-(4-Chlorophenyl)-3-pyridyl]methanol 0.335 g of Pd(Ph3)4, 0.453 g of 4-chlorophenylboronic acid and then 2.9 ml of a 2M aqueous Na2CO3 solution are added in succession to a suspension of 0.545 g of the compound of Step A in a mixture of DME/EtOH (7.5 ml/3 ml). The whole is degassed under argon for 15 minutes and then heated at 80 C. for 18 hours. The reaction mixture is then filtered at ambient temperature. The filtrate is then hydrolyzed and extracted with CH2Cl2. The organic phases are combined, washed with a saturated NaCl solution and then dried over magnesium sulphate and concentrated to dryness. The resulting solid is finally purified by chromatography over silica gel (CH2Cl2/MeOH) to yield the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 44-Chlorophenylboronic acid (13.2 g, 0.08 mol) and tetrakis(triphenylphosphine) palladium (0) (2.4 g, 0.002 mol) are added to a solution of <strong>[14922-91-9]5-bromo-2-ethylaniline</strong> (14.1 g, 0.07 mol) in 1 ,2- dimethoxyethane (140 ml). After stirring the reaction mixture for 15 minutes at 2O0C, a solution of 20% aqueous sodium carbonate (300ml) is added to the mixture, and the resulting mixture is refluxed for 24 hours. The reaction mixture is cooled to room temperature, diluted with water and extracted using ethyl acetate. The combined organic extracts are dried over anhydrous sodium sulfate, filtered and the filtrate evaporated in vacuo. The residue is further purified by column chromatography on silica gel, eluting with 5% ethyl acetate in hexane to give 5-(4-chlorophenyl)- 2-ethylaniline (14.3 g). | ||
4-Chlorophenylboronic acid (13.2 g, 0.08 mol) and tetrakis(triphenylphosphine) palladium (0) (2.4 g, 0.002 mol) are added to a solution of <strong>[14922-91-9]5-bromo-2-ethylaniline</strong> (14.1 g, 0.07 mol) in 1 ,2- dimethoxyethane (140 ml). After stirring the reaction mixture for 15 minutes at 2O0C, a solution of <n="73"/>20% aqueous sodium carbonate (300ml) is added to the mixture, and the resulting mixture is refluxed for 24 hours. The reaction mixture is cooled to room temperature, diluted with water and extracted using ethyl acetate. The combined organic extracts are dried over anhydrous sodium sulfate, filtered and the filtrate evaporated in vacuo. The residue is further purified by column chromatography on silica gel, eluting with 5% ethyl acetate in hexane to give 5-(4-chlorophenyl)- 2-ethylaniline (14.3 g). | ||
Step 44-Chlorophenylboronic acid (13.2 g, 0.08 mol) and tetrakis(triphenylphosphine) palladium (0) (2.4 g, 0.002 mol) are added to a solution of <strong>[14922-91-9]5-bromo-2-ethylaniline</strong> (14.1 g, 0.07 mol) in 1 ,2- dimethoxyethane (140 ml). After stirring the reaction mixture for 15 minutes at 20C, a solution of 20% aqueous sodium carbonate (300ml) is added to the mixture, and the resulting mixture is refluxed for 24 hours. The reaction mixture is cooled to room temperature, diluted with water and extracted using ethyl acetate. The combined organic extracts are dried over anhydrous sodium sulfate, filtered and the filtrate evaporated in vacuo. The residue is further purified by column chromatography on silica gel, eluting with 5% ethyl acetate in hexane to give 5-(4-chlorophenyl)- 2-ethylaniline (14.3 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Method N:Synthesis of (S)-l-(4-Chloro-phenyl)-6-oxo-piperidine-2-carboxylic acid (3-tert-butgammal- isoxazol-5-yl)-amide (Example 131):Step 1: Synthesis of (S)-l-(4-Chloro-phenyl)-6-oxo-piperidine-2-carboxylic acidTo a stirred suspension of (S)-l-(4-chloro-phenyl)-6-oxo-piperidine-2-carboxylic acid (1.368g, 9.558mmol) in 1,2-dichloroethane (35 rnL) l,8-diazabicyclo[5,4,0]undec-7-ene (DBU) (3.ImL, 20.854mmol) is added at room temperature. After 10 min di-mu-hydroxy- bis[N,N,N',N'-tetramethylenediamine)-copper (II) chloride (Cu-TMEDA) (1.614g, 3.476mmol) is added to the clear solution. The mixture is stirred for 10 min and A- chlorophenylboronic acid (1.495g, 9.558mmol) is added. After 20 h solvent is evaporated in vacuo, the concentrate taken up in saturated sodium bicarbonate solution (15OmL) and the aqueous layer is washed with ethyl acetate (3XlOOmL). The aqueous layer is treated with 1 N hydrochloric acid to pH 2 and extracted with ethyl acetate (3XlOOmL). Combined organic extracts washed with brine (2X50mL), dried over anhydrous sodium sulfate and solvent removed in vacuo to give the title compound as an off-white solid, m/z 254 [M+H+] . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 20 - 80℃; for 4.42h;Inert atmosphere; | Example 13; A solution of <strong>[350597-49-8]5-chloro-2-methyl-nicotinic acid methyl ester</strong> (1.0 equiv.) is treated with 1 ,2-dimethoxyethane and 4-chlorophenyl boronic acid (1.05 eq.). This is followed by Pd(PPli3)4 (0.1 eq., Aldrich) at room temperature. After the reaction mixture is purged with Argon for 15 minutes, aqueous saturated NaHCO3 (2.0 equiv.) is added and the resulting solution is purged with argon for another 10 min. The resulting reaction mixture is then heated under nitrogen atmosphere at 80 0C for 4 h to produce the desired adduct. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 77℃; for 42h;Inert atmosphere; | In argon atmosphere, a mixture of Intermediate A-3 synthesized in the step (A-3) (309 g, 1.25 mol), 4-chlorophenylboronic acid (353 g, 2.26 mol), tetrakis(triphenylphosphine) palladium(0) (29 g, 25 mmol), sodium carbonate (398 g, 3.76 mol), DME (1.9 L), and water (1.9 L) was stirred at 77 C. for 42 h. The reaction liquid was cooled to room temperature. After adding water, the reaction liquid was extracted with ethyl acetate, and the organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography and recrystallization to obtain Intermediate B (255 g). The yield was 73%. |
60% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 12h;Reflux; Inert atmosphere; | <Synthesis Example 26 (Synthesis of Intermediate 26)>; Under the atmosphere of argon gas, 1000 ml of toluene and 500 ml of 2 M concentration sodium carbonate aqueous solution was added to 120.0 g (399 mmol) of 1-bramo-3-fluaro-4-iodobromobenzene, 72.7 g (479 mmol) of 2-methoxyphenyl boronic acid sand 9.2 g (7.96 mmol) of tetrakis(triphenylphosphine) palladium (0), and the resultant mixture solution was heated while being refluxed for 10 hours. After the reaction was completed, extraction with toluene was carried out immediately and a water layer was removed. After drying the organic layer over sodium sulfate, the resultant was condensed. The residue was subjected to a chromatography purification using a silica gel column to obtain 89.6 g of 4-bromo-2-fluoro-2'-methoxybiphenyl in the state of white crystal (yield: 80%). Under the atmosphere of argon gas, of 900 ml of dichloromethane was added to 89.6 g (319 mmol) of 4-bromo-2-fluoro-2'-methoxybiphenyl, and the resultant mixture solution was stirred while cooling with ice. After adding 95.9 g (382 mmol) of boron tribromide by dropping, the solution was stirred at a room temperature for 12 hours. After completion of the reaction, 200 ml of water was added, and the resultant mixture solution was stirred for 1 hour, followed by removing a water layer. After drying the organic layer over magnesium sulfate, the resultant was condensed. The residue was subjected to a chromatography purification using a silica gel column to obtain 68.1 g of 4-bromo-2-fluoro-2'-hydroxybiphenyl in the state of white crystal (yield: 70%). Onto 68.1 g (255 mmol) of 4-bromo-2-fluoro-2'-hydroxybiphenyl and 70.4 g (510 mmol) of potassium carbonate, 1500 ml of N-methylpyrrolidone was added and the resultant solution was stirred at 180C for 3 hours. After completion of the reaction, water was added and extraction by toluene was conducted. After drying an organic layer over sodium sulfate, the resultant was condensed. The resultant residue was re-crystallized through toluene and 44.2 g of <strong>[26608-06-0]3-bromodibenzofuran</strong> in the state of white crystal was obtained (yields:60%). Under the atmosphere of argon gas, 350 ml of toluene and 170 ml of 2 M concentration sodium carbonate aqueous solution was added to 34.2 g (138 mmol) of 3-bromobenzofram, 26.0 g (166 mmol) of 4-chlorophenyl boronic acid and 3.2 g (2.77 mmol) of tetrakis(triphenylphasphine)palladium (0), and the resultant mixture solution was heated while being refluxed for 12 hours. After the reaction was completed, filtration was carried out immediately and a water layer was removed. After drying the organic layer over sodium sulfate, the resultant was concentrated. The residue was subjected to a chromatography purification using a silica gel column to obtain 23.1 g of white crystal (yield:60%). The resultant white crystal was identified as Intermediate 26 from the result in accordance with the FD-MS analysis. |
60% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 12h;Inert atmosphere; Reflux; | <Synthesis Example 2-21 (synthesis of Intermediate 2-21) > Under an argon atmosphere, 350 mL of toluene and 170 mL of an aqueous solution of sodium carbonate having a concentration of 2 M were added to 34.2 g (138 mmol) of Intermediate 2-20, 26.0 g (166 mmol) of 4-chlorophenyl boronic acid, and 3.2 g (2.77 mmol) of tetrakis(triphenylphosphine)palladium(0), and then the mixture was heated while being refluxed for 12 hours. Immediatelyafterthe completionof the reaction, the resultant was filtrated, and then the aqueous layer was removed. The organic layer was dried with sodium sulfate, and was then concentrated. The residue was purified by silica gel column chromatography. Thus, 23.1 g of a white crystal were obtained (in 60% yield). The crystal was identified as Intermediate 2-21 by FD-MS analysis. |
60% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 12h;Inert atmosphere; Reflux; | Under an argon atmosphere, 350 mL of toluene and 170 mL of an aqueous solution of sodium carbonate having a concentration of 2 M were added to 34.2 g (138 mmol) of the Intermediate 27, 26.0 g (166 mmol) of 4-chlorophenylboronic acid, 3.2 g (2.77 mmol) of tetrakis (triphenylphosphine)palladium (0), and then the mixture was heated for 12 hours while being refluxed. Immediatelyafter the completion of the reaction, the resultant was filtrated, and then the aqueous layer was removed. The organic layer was dried with sodium sulfate, and was then concentrated. The residue was purified by silica gel column chromatography. Thus, 23.1 g of a white crystal were obtained (in 60% yield). The crystal was identified as the Intermediate 28 by FD-MS analysis. |
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 12h;Inert atmosphere; Reflux; | Under an argon atmosphere, 34.2 g of <strong>[26608-06-0]3-bromodibenzofuran</strong>, 26.0 g of 4-chlorophenyl boronic acid, 3.2 g of tetrakis(triphenylphosphine)palladium, 350 ml of toluene, and 170 ml of an aqueous solution of sodium carbonate having a concentration of 2 M were loaded into a 1,000-ml three-necked flask, and then the mixture was heated for 12 hours while being refluxed. Immediately after the completion of the reaction, the resultant was filtrated, and then the aqueous layer was removed. The organic layer was dried with sodium sulfate, and was then concentrated. The residue was purified by silica gel column chromatography. Thus, 23.1 g of a white crystal were obtained. The crystal was identified as the intermediate-17' by FD-MS analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 80℃; for 6h;Inert atmosphere; | General procedure: A 1,4-dioxane solution (3 mL) of 1, arylboronic acid (1.2 equiv), aqueous K2CO3 (2.0 M, 1.0 mL) and Pd(PPh3)4 (3 mol percent) was heated at 80 °C for 6 h under argon atmosphere. After cooling to 20 °C, H2O was added and the reaction mixture was extracted with CH2Cl2 (3×25 mL). The organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, heptane/EtOAc).#10; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 120℃; for 8h;Inert atmosphere; | General procedure: A 1,4-dioxane solution (3 mL) of 1, arylboronic acid (2.2 equiv), aqueous K2CO3 (2.0 M, 1.0 mL) and Pd(PPh3)4 (6 mol percent) was heated at 120 °C for 8 h under argon atmosphere. After cooling to 20 °C, H2O was added and the reaction mixture was extracted with CH2Cl2 (3×25 mL). The organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, heptane/EtAOc).#10; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With pyridine; copper diacetate; for 16h;Molecular sieve; | To a mixture of methyl-4-Boc-piperazine-2-carboxylate (2.2 g, 9.0 mmol), molecular sieves (4 A, 2.2 g), pyridine (1.46 ml_, 18.0 mmol) and (4- chlorophenyl)boronic acid (2.81 g, 18.0 mmol) was added copper(ll) acetate (1.63 g, 9.0 mmol). The reaction mixture was stirred for 16 h under an atmosphere of dry air and concentrated in vacuo. The residue was taken up in ethyl acetate (250 ml.) and filtered through a pad of diatomaceous earth. The filtrate was concentrated in vacuo and residue was purified by column chromatography (0-30% gradient of ethyl acetate in hexanes) to afford 1-ferf-butyl 3-methyl 4-(4-chlorophenyl)piperazine-1 ,3- dicarboxylate in 36% yield (1.16 g) as a colorless solid: Eta NMR (300 MHz, CDCI3) delta 7.21-7.16 (m, 2H), 6.79-6.74 (m, 2H), 4.51 (d, J =13.7 Hz, 1 H), 4.31 (br s, 1 H), 4.20- 4.02 (m, 1 H), 3.63 (s, 3H), 3.54-3.42 (m, 1 H), 3.37-3.25 (m, 2H), 3.15-2.98 (m, 1 H), 1.44 (s, 9H); MS (ES+) m/z 298.8 (M - 56), 300.8 (M - 56). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 95℃; for 6.0h;Inert atmosphere; | The compound number 274 was prepared as follows. To a solution of 5-chloro-2-nitroaniline (50 g, 289.74 mmol) in AcOH (200 ml) was added NIS (63 g, 280.02 mmol) with stirring overnight at room temperature. Then the solids were collected by filtration and washed with water (50 ml). The solid was dried in an oven under reduced pressure to afford <strong>[335349-57-0]5-chloro-4-iodo-2-nitroaniline</strong> as a yellow solid (70 g, 81%). Next, to a solution of <strong>[335349-57-0]5-chloro-4-iodo-2-nitroaniline</strong> (15 g, 50.26 mmol) in dioxane (200 ml) and water (20 ml) was added (4-chlorophenyl)boronic acid (15.7 g, 100.40 mmol), K3PO4 (21.2 g, 99.87 mmol) and Pd(PPh3)4 (3 g, 2.60 mmol) with stirring for 6 h at 95 C. maintained with an inert atmosphere of nitrogen. Then the resulting mixture was concentrated under vacuum to give a residue, which was purified by a silica gel column with 5%10% ethyl acetate in petroleum ether to afford 5-chloro-4-(4-chlorophenyl)-2-nitroaniline as a yellow solid (9 g, 63%). To a solution of 5-chloro-4-(4-chlorophenyl)-2-nitroaniline (12 g, 42.39 mmol) in ethanol (150 ml) was added hydrogen chloride (conc, 10 ml) to this was followed by the addition of Zn powder (16.6 g, 253.34 mmol) in portions at room temperature. The resulting solution was stirred for 4 h at 85 C. Then the resulting mixture was concentrated under vacuum, dissolved in water (200 ml) and extracted with ethyl acetate (3×200 ml). The combined organic layers was dried and concentrated under vacuum to give a residue, which was purified by a silica gel column with 10%20% ethyl acetate in petroleum ether to produce 4-chloro-5-(4-chlorophenyl)benzene-1,2-diamine as an off-white solid (8.7 g, 81%). Finally, a solution of 4-chloro-5-(4-chlorophenyl)benzene-1,2-diamine (7 g, 27.65 mmol) in heptafluorobutanoic acid (70 ml) was stirred for 1.5 h at 120 C. Then the mixture was poured into water (200 ml), adjusted pH value of the solution to 7 with aqueous sodium bicarbonate and extracted with ethyl acetate (3×200 ml). The combined organic layers was dried over anhydrous magnesium sulfate and concentrated under vacuum to give a residue, which was purified by a silica gel column with 5% ethyl acetate in petroleum ether to afford 5-chloro-6-(4-chlorophenyl)-2-(heptafluoropropyl)-1H-1,3-benzodiazole as an off-white solid (7.3977 g, 62%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 16.0h;Inert atmosphere; | 5-Bromo-6-methylpyridine-2,3-diamine (50 mg, 0.25 mmol), 4-chlorophenylboronicacid (45 mg, 0.29 mmol), and cesium carbonate (240 mg, 0.74 mmol) were suspendedin dioxane/water (4:1; v/v) (1.25 ml) and this mixture was degassed (3 x vacuumnitrogen cycles). [1,1 ?-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1:1)dichloromethane complex was added and the mixture degassed again (3 x vacuum30 nitrogen cycles). The resulting reaction mixture was stirred at 110 00 for 16 h. Then, the mixture was allowed to cool and it was worked-up adding chloroform and washing with water and brine. The organic phase was dried and evaporated under reduced pressure to afford a residue of 93 mg. This crude material was purified by flash chromatography (methanol-dichloromethane gradient, 0:100 rising to 10:90) to give 46mg (0.20 mmol, 80percent yield) of the title compound as a solid. Purity 95percent.1H NMR (400 MHz, CHLOROFORM-d) oe ppm 7.35 (d, 2H, J = 8.3 Hz), 7.20 (d, 2H, J =8.3 Hz), 6.78 (s, 1 H), 4.30 (br.s, 2H), 3.23 (br.s, 2H), 2.28 (s, 3H)UPLC/MS (3mm) retention time 1.08 mm.LRMS: m/z 234 (M+1, ixCI). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | (2) 9.67 g (0.03 mol) of 9- (2-bromophenyl) carbazole,Chlorophenylboronic acid(0.081mol) of 5.01g (0.032mol) potassium carbonate and 100mL of solvent (toluene: EtOH: H2O = 10: 2: 1) were placed in a reactor, stirred and replaced with nitrogen for 30min. Pd2 (dba) 3 0.055 g, X-phos 0.029g, heated to reflux, 4h, TLC no raw material, add water and finallyThe reaction was stopped and the aqueous layer was separated. The organic layer was filtered to remove the catalyst through silica gel. The solvent was distilled off under reduced pressure, the mixture was cooled to 15 ° C and suction-filtered. The residue was vacuum-dried to obtain 9.76 g of a solid9- (4'-Chlorobiphenyl-2-yl) carbazole 92percent yield. | |
72% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; for 6h;Reflux; Inert atmosphere; | Under a nitrogen atmosphere,In a 1 L round bottom flask,The compound 9- (2-bromophenyl) -9H-carbazole(20.0 g, 62.31 mmol),(4-chlorophenyl) boronic acid(10.21 g, 65.42 mmol)After completely dissolved in 360ml of tetrahydrofuran,2M potassium carbonate aqueous solution (180 ml) was added,After tetrakis-(triphenylphosphine) palladium (2.16 g, 1.87 mmol) was added,The mixture was heated and stirred for 6 hours. The temperature is reduced to room temperature,The water layer is removed,After drying over anhydrous magnesium sulfate,Concentrated under reduced pressure,Tetrahydrofuran was used240ml for recrystallization,Compound D (15.79 g, 72percent) was prepared. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | A mixture of N-boc-2-(4-bromophenyl)ethylamine, the desiredarylboronic acid (a-m) (1.2 equiv), tetrakis(triphenylphosphine)-palladium(0) (0.04 equiv), Na2CO3 (5 equiv) in degassed toluene/H2O (5/2) was refluxed for 18 h. The reaction mixture was filteredthrough Celite and concentrated in vacuo. The resulting residuewas dissolved in in EtOAc (200 mL), washed with H2O (200 mL 2) and brine (200 mL). The organic layer was dried with anhydrousNa2SO4 and concentrated in vacuo. The residue was purified by columnchromatography on SiO2. Using Method E, 13 (1.50?g, 5.0?mmol), 4-chlorophenylboronic acid (0.94?g, 6.0?mmol), tetrakis(triphenylphosphine)palladium(0) (0.23?g, 0.2?mmol), Na2CO3 (2.65?g, 25.0?mmol) in toluene/H2O (50?ml/20?ml), followed by 4.0?M HCl in dioxane (3.75?ml, 15.0?mmol) gave 14h as a white solid (0.94?g, 69%): Rf?=?0.00 (EtOAc 9: acetone 1): 1H NMR (DMSO-d6, 400?MHz) delta 2.99-3.06 (m, NH3CH2CH2), 7.37-7.77 (m, 8 ArH), 8.31 (s, NH3); 13C NMR (DMSO-d6, 75?MHz) delta 33.0 (NCH2CH2), 127.3, 128.7, 129.3, 129.8, 132.7, 137.6, 137.7, 139.1 (12 ArC). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With potassium phosphate; palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In tetrahydrofuran; at 50℃; for 14h;Sealed tube; Inert atmosphere; | General procedure: The desired amount of substrate, boronic acid (3 equiv), base (3equiv), Pd(OAc)2 (2.5 molpercent) and ligand (5 molpercent) were weighed out as solids, the vial was sealed and purged with argon, then solvent was added and the vial was purged again. The reactions were run for 14 h at the specified temperature. The crude material was filtered through a pad of Celite and washed three times with CHCl3. The solvent was removed under reduced pressure, an internal standard was added and the reaction was analysed by 1H NMR spectroscopy. For purification, the analysed mixture was concentrated, the product extracted with Et2O and filtered through anhydrous MgSO4 and further purified by flash column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 110℃;Inert atmosphere; | Under nitrogen, one equivalent (eq)Compound A, 2 equivalents of compound B, 0.002 equivalents of Pd(PPh3)4, 2 equivalents of K2CO3 (aq), and THF were introduced into a round-bottomed flask in one go and under reflux,The resultant was stirred at 110 °C.The reaction solution is cooled to room temperature.And then separating the organic layer,Vacuum dried and purified using column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With trisodium tris(3-sulfophenyl)phosphine; palladium diacetate; sodium carbonate; In water; acetonitrile; at 100℃;Inert atmosphere; | General procedure: 31 (1 eq.), boronic acid (1.5 eq.) or pinacol ester [for compound14 (1.5 eq.)], Na2CO3 (9 eq.), Pd(OAc)2 (0.05 eq.) and TPPTS (0.15 eq.)were added to a 10mL round-bottom flask, equipped with a stir bar.Next, the flask was evacuated and refilled with argon. This procedure was repeated three times in total. Next, degassed MeCN(2 mL/mmol SM) and H2O (4 mL/mmol SM) were added to the solids under argon. After 5 min of stirring, the mixture was heatedto 100 C in a pre-heated oil bath. When the starting material was fully consumed (usually 1e3 h), the mixture was cooled to ambient temperature, and neutralized (pH ~ 7) with 0.5M aq. HCl. Themixture was evaporated till dryness, resuspended in MeOH and evaporated (three times). Next, the mixture was adsorbed onto Celite (fromMeOH) and eluted over a short silica pad (~5 cm) with 20% MeOH/DCM. The liquid was evaporated in vacuo and purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; silver(l) oxide; In tert-Amyl alcohol; at 50℃; for 20h;Inert atmosphere; | General procedure: Amixture of phenylboronic acid (1a) (1 mmol, 122 mg), alpha-trifluoromethylacrylicacid (2) (0.5 mmol, 70 mg), [Cp*RhCl2]2 (0.01 mmol, 6 mg), AgSbF6 (0.1 mmol, 34mg), Ag2O (1 mmol, 232 mg), and 1-methylnaphthalene (ca. 40 mg) as internal standard was stirred in tert-amylalcohol (3 ml) under argon at 50 C for 20 h.Then the reaction mixture was diluted by ethyl acetate (30 ml). The organiclayer was washed by 1 N HCl(30 ml), water 30 (ml), and brine (30 ml) and driedover Na2SO4. After evaporation of the solvents under vacuum, product 3a? (101 mg,93%) was isolated by column chromatography on silica gel usinghexane/EtOAc/AcOH=90/9/1 (v/v/v) as eluent. |
Tags: 1679-18-1 synthesis path| 1679-18-1 SDS| 1679-18-1 COA| 1679-18-1 purity| 1679-18-1 application| 1679-18-1 NMR| 1679-18-1 COA| 1679-18-1 structure
A153220 [151169-75-4]
3,4-Dichlorophenylboronic acid
Similarity: 0.95
A205014 [67492-50-6]
3,5-Dichlorophenylboronic acid
Similarity: 0.93
A163466 [68716-47-2]
2,4-Dichlorophenylboronic acid
Similarity: 0.89
A153220 [151169-75-4]
3,4-Dichlorophenylboronic acid
Similarity: 0.95
A205014 [67492-50-6]
3,5-Dichlorophenylboronic acid
Similarity: 0.93
A163466 [68716-47-2]
2,4-Dichlorophenylboronic acid
Similarity: 0.89
A153220 [151169-75-4]
3,4-Dichlorophenylboronic acid
Similarity: 0.95
A205014 [67492-50-6]
3,5-Dichlorophenylboronic acid
Similarity: 0.93
A163466 [68716-47-2]
2,4-Dichlorophenylboronic acid
Similarity: 0.89
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