Structure of 71597-85-8
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Campbell, Allea ; Alsudairy, Ziad ; Dun, Chaochao ; Akram, Fazli ; Smith-Petty, Kayla ; Ambus, Abrianna , et al.
Abstract: Covalent organic framework (COF)-supported palladium catalysts have garnered enormous attention for cross-coupling reactions. However, the limited linkage types in COF hosts and their suboptimal catalytic performance have hindered their widespread implementation. Herein, we present the first study immobilizing palladium acetate onto a dioxin-linked COF (Pd/COF-318) through a facile solution impregnation approach. By virtue of its permanent porosity, accessible Pd sites arranged in periodic skeletons, and framework robustness, the resultant Pd/COF-318 exhibits exceptionally high activity and broad substrate scope for the Suzuki-Miyaura coupling reaction between aryl bromides and arylboronic acids at room temperature within an hour, rendering it among the most effective Pd/COF catalysts for Suzuki-Miyaura coupling reactions to date. Moreover, Pd/COF-318 demonstrates excellent recyclability, retaining high activity over five cycles without significant deactivation. The leaching test confirms the heterogeneity of the catalyst. This work uncovers the vast potential of dioxin-linked COFs as catalyst supports for highly active, selective, and durable organometallic catalysis.
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Keywords: covalent organic framework (COF) ; dioxin-linked COF ; Pd(II) immobilization ; Suzuki-Miyaura coupling
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Purchased from AmBeed: 24067-17-2 ; 98-80-6 ; 3375-31-3 ; 71597-85-8 ; 4877-80-9 ; 99768-12-4
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Guo, Sheng ; Wu, Yifan ; Luo, Shao-Xiong Lennon ; Swager, Timothy M. ;
Abstract: Heterogenous catalysts with confined nanoporous catalytic sites are shown to have high activity and size selectivity. A solution-processable nanoporous organic polymer (1-BPy-Pd) catalyst displays high catalytic performance (TON > 200K) in the heterogeneous Suzuki–Miyaura coupling (SMC) reaction and can be used for the preparation of the intermediates in the synthesis of pharmaceutical agents. In comparison to the homogeneous catalyst analogue (2,2′-BPy)PdCl2, the heterogenous system offers size-dependent catalytic activity when bulkier substrates are used. Furthermore, the catalyst can be used to create catalytic impellers that simplify its use and recovery. We found that this system also works for applications in heterogenous Heck and nitroarenes reduction reactions. The metal-binding nanoporous polymer reported here represents a versatile platform for size-selective heterogeneous and recyclable catalysts.
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Keywords: nanoporous organic polymer ; heterogeneous catalyst ; Suzuki−Miyaura coupling reaction ; size-selective reaction ; catalyst processing
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Purchased from AmBeed: 128796-39-4 ; 10365-98-7 ; 98-80-6 ; 556-96-7 ; 171663-13-1 ; 71597-85-8 ; 402-43-7 ; 2042-37-7 ; 22385-77-9 ; 16419-60-6 ; 15862-18-7 ; 87199-15-3 ; 171408-84-7 ; 643-58-3 ; 591-50-4 ; 76911-73-4 ; 398-36-7 ; 14871-92-2 ; 5720-07-0 ; 945976-76-1 ; 366-18-7 ; 2920-38-9 ; 623-00-7 ; 24973-49-7 ; 588-59-0 ; 128796-39-4 ; 5723-93-3 ; 17057-88-4 ; 126485-55-0
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Pieterse, Lianie ; Beteck, Richard M. ; Baratte, Blandine ; Jesumoroti, Omobolanle J. ; Robert, Thomas ; Ruchaud, Sandrine , et al.
Abstract: Protein kinases, including CDK9/CyclinT and Haspin, are regarded as potential drug targets in cancer therapy. Findings from a previous study suggested 7-azaindole as a privileged scaffold for producing inhibitors of CDK9/CyclinT and Haspin. Inspired by these findings, the current study synthesized and evaluated thirteen (13) C6-substituted 7-azaindole and twenty (20) C4-substituted structurally related 7H-pyrrolo[2,3-d]pyrimidine derivatives against a panel of protein kinases, including CDK9/CyclinT and Haspin. Eleven of the 7H-pyrrolo[2,3-d]pyrimidine derivatives exhibited activity toward CDK9/CyclinT, while 4 of compounds had activity against Haspin. The best CDK9/CyclinT (IC50 of 0.38 μM) and Haspin (IC50 of 0.11 μM) activities were achieved by compounds 7d and 7f, resp. Hence, these compounds may be valuable starting points for development of new anti-cancer drugs.
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Keywords: 7-Deazapurine ; Anticancer ; CDK9/CylinT ; Haspin ; Protein kinase
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Purchased from AmBeed: 98437-24-2 ; 71597-85-8 ; 3680-69-1 ; 6165-68-0 ; 51067-38-0 ; 87199-18-6
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CAS No. : | 71597-85-8 |
Formula : | C6H7BO3 |
M.W : | 137.93 |
SMILES Code : | C1=C(C=CC(=C1)O)B(O)O |
MDL No. : | MFCD01074628 |
InChI Key : | COIQUVGFTILYGA-UHFFFAOYSA-N |
Pubchem ID : | 2734360 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 3.0 |
Molar Refractivity | 38.29 |
TPSA ? Topological Polar Surface Area: Calculated from |
60.69 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 |
0.47 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.93 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.36 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.2 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.4 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.37 |
Solubility | 5.89 mg/ml ; 0.0427 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.31 |
Solubility | 6.7 mg/ml ; 0.0486 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.68 |
Solubility | 28.6 mg/ml ; 0.207 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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.81 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 |
---|---|---|
100% | With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In DMF (N,N-dimethyl-formamide); water; at 80℃; for 16h; | A solution of the product of preparation 49 (0.75 g, 2.25 mmol), 4-hydroxy phenylboronic acid (0.62 g, 4.50 mmol) and 1, 1'- bis (diphenylphosphino) ferrocenyl palladium (II) chloride (0.11 g, 0.14 mrnol) in N, N-dimethylformamide (14 mL) was treated with 2M aqueous sodium carbonate solution (4 mL) and the resulting mixture was heated at 80 C for 16 hours. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel, eluting with ethyl acetate: pentane, 25: 75, to afford the title compound as a pale pink crystalline solid in quantitative yield, 0. 73 g. 'H NMR (400MHz, CDCI3) 8 : 1.47 (9H, s), 4. 33-4. 41 (2H, m), 4. 87-4. 94 (1H, bs), 6.89 (2H, d), 7.21 (1H, d), 7.37 (1H, dd), 7.43-7. 45 (4H, m); LRMS ESI m/z 298 [M-H]- |
With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In DMF (N,N-dimethyl-formamide); water; at 80℃; for 16h; | A solution of the iodide from preparation 61 (0.75g, 2.25 mmol), 4-hydroxy phenylboronic acid (0.62g, 4.50 mmol), 1,1'-bis(diphenylphosphino)ferrocenyl palladium(II)chloride (0.11g, 0.14 mmol), in N,N-dimethylformamide (14 ml) was treated with 2M aqueous sodium carbonate (4 ml) and the resulting mixture heated at 80 C. under a nitrogen atmosphere for 16 hours. The solvent was removed in vacuo and the residue purified by column chromatography on silica gel eluting with ethyl acetate:pentane (1:3) to give the title compound as a pale pink crystalline solid (0.73g). 1HNMR (400 MHz, CDCl3) delta: 1.47 (s, 9H), 4.33-4.41 (m, 2H), 4.87-4.94 (bs, 1H), 6.89 (d, 2H), 7.21 (d, 1H), 7.37 (dd, 1H), 7.43-7.45 (m, 4H) ppm. MS (electrospray) m/z 298 [M-H]-, 322 [M+Na]+ | |
With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In DMF (N,N-dimethyl-formamide); water; at 80℃; for 16h; | A solution of the iodide from preparation 131 (0.75 g, 2.25 mmol), 4-hydroxy phenylboronic acid (0.62 g, 4.50 mmol), 1,1'-Bis(diphenylphosphino)ferrocenyl palladium(II)chloride (0.11 g, 0.14 mmol), in N,N-dimethylformamide (14 ml) was treated with 2M aq. sodium carbonate (4 ml) and the resulting mixture heated at 80 C. under a nitrogen atmosphere for 16 hours. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel eluting with ethyl acetate:pentane (1:3) to give the title compound as a pale pink crystalline solid (0.73 g). 1HNMR (400 MHz, CDCl3) delta: 1.47 (s, 9H), 4.33-4.41 (m), 4.87-4.94 (bs, 1H), 6.89 (d, 2H), 7.21 (d, 1H), 7.37 (dd, 1H), 7.43-7.45 (m, 4H) ppm. MS (electrospray) m/z 298 [M-H]-, 322 [M+Na]+ |
With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In DMF (N,N-dimethyl-formamide); water; at 80℃; for 16h; | A solution of the iodide from preparation 75 (0.75g, 2.25mmol), 4-hydroxy phenylboronic acid (0.62g, 4.50mmol), 1,1'-bis(diphenylphosphino)ferrocenyl palladium(ll)chloride (0.11g, 0.14mmol), in A/,A/-dimethylformamide (14ml) wastreated with 2M aq. sodium carbonate (4ml) and the resulting mixture heated at 80C under a nitrogen atmosphere for 16 hours. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel eluting with ethyl acetate:pentane (1:3) to give the title compound as a pale pink crystalline solid ( 0.73g).1HNMR (400MHz, CDCI3) 5 : 7.43-7.45 (m, 4H), 7.37 (dd, 1H), 7.21 (d, 1H), 6.89 (d, 2H), 4.87-4.94 (bs, 1H), 4.33-4.41 (m, 2H), 1.47 (s, 9H) ppm.MS (electrospray) m/z 298 [M-H]", 322 [M+Naf |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Preparation 12 : tert-Butyl [(4'-hydroxybiphenyl-3-yl)methyl]carbamate; Nitrogen was bubbled through a stirred solution of the bromide from preparation 11 (5.12Kg; 17.9 mol), 4-hydroxyphenylboronic acid (2.71 Kg; 19.7 mol) and sodium carbonate (2.848Kg; 26.8 mol) in a mixture of 1 ,4 dioxane (25.6L) and demineralised water (25.6L) at 20 to 250C for 1 hour. Then 1,1'-/s(diphenylphosphino)ferrocenyl palladium(ll)chloride(14.6g; 0.0179 mol) was added to the mixture and the nitrogen bubbling was continued for a further 30 minutes. Subsequently, the reaction was heated at 65 to 7O0C under a nitrogen blanket for 2 hours. The reaction was cooled to 20 to 25C, ethyl acetate (41 L) was added and the resulting mixture was stirred vigorously for 10 minutes, the phases were then separated. The organic phase was washed with a solution of citric acid (1.9Kg) in demineralised water (18.9L) followed by a solution of sodium chloride (3.15Kg) in demineralised water (18.9L). The ethyl acetate solution was treated with activated carbon (Darco KB 100mesh, wet powder; 5.12Kg) and stirred for 12 hours. The EPO <DP n="35"/>resulting slurry was then filtered through Arbocel and the cake was washed with methanol (25.6L). The combined filtrate was distilled and replaced with toluene under reduced pressure at 40 to 500C to a final volume of approximately 15L. The solution was then cooled to 10C over 2 hours and the resulting suspension was stirred at 1O0C for 12 hours. The product was isolated by filtration and washed with cyclohexane (2 x 2.56L) to provide the title compound as a white solid (4.26 Kg).1H NMR (400MHz1 CDCI3) delta: 1.47 (s, 9H), 4.33-4.41 (m, 2H), 4.87-4.94 (bs, 1H), 6.89 (d, 2H), 7.21 (d, 1H), 7.37 (dd, 1H), 7.43-7.45 (m, 4H) ppm. MS (electrospray) m/z 298 [M-H]", 322 [M+Na]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 2h;Heating / reflux; | Example 1 : {6-[4-(2-MorphoIin-4-yl-ethoxy)-phenyl]-quinazoIin-4-yI}-(4- morphoIin-4-yI-phenyI)-amine Step 1: 4-Amino-4'-(2-morphoIin-4-yl-ethoxy)-biphenyl-3-carbonitriIeA mixture of intermediate 1 ( 0.5g) 4-hydroxyphenylboronic acid (565mg) and tetrakis (triphenylphosphine) palladium (0) (290mg) in DME / 2M aqueous sodium carbonate (2:1, 15ml) was heated at reflux for 2hr. The cooled mixture was diluted with ethyl EPO <DP n="18"/>acetate and washed with further aqueous base. The organic phase was dried (MgSO4) and reduced onto silica gel. Flash chromatography with CH2Cl2 to 5% methanol in CH2Cl2 as eluant gave the coupling product, slightly contaminated with triphenylphosphine oxide by NMR. This material (340mg) was heated with 2- chloroethyl morpholine hydrochloride (330mg) and potassium carbonate (670mg) in acetone (20ml) at reflux overnight. The cooled reaction was partitioned between CH2Cl2 and 2M hydrochloric acid (aq). The acid phase was separated, basified and extracted with CH2Cl2 (2x),. These organic washes were concentrated to give the title compound as a brown solid (342mg) LC-MS rt 2.15 M+ 3241H NMR delta 7.55 (2H, m) ,7.38 (2H, d, J 8.21Hz), 6.95 ( 2H, d, J 8.21Hz), 6.78 (IH, m), 4.24 ( 2H, br s) 4.14 (2H, t, J 6.3Hz), 3.72 (4H, m), 2.82 (2H, m), 2.59 (4H5 m) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With water; sodium carbonate;tetrakis(triphenylphosphine) palladium(0); tetrabutylammomium bromide; In ethanol; toluene; at 100℃; | 4-(6-aminonaphthalen-2-yl)phenol (16)Palladium tetrakis(triphenylphosphine) (34.7 mg, 0.03 mmol) was added to a solution of compound 15 (200 mg, 0.9 mmol) and 4-hydroxyphenylboronic acid (165.5 mg, 1.2 mmol) in a mixed solvent of toluene (15 ml) and ethanol (5 ml), followed by the addition of tetrabutyl ammonium bromide (19 mg, 0.06 mmol) and sodium carbonate (2M aq., 4.0 ml). The solution was degassed by bubbling nitrogen for 10 min and then heated at 100 0C overnight. After cooling down to room temperature, the mixture was partitioned between ethyl acetate and water. <n="55"/>Organic layer was separated, washed with brine, dried over sodium sulfate and concentrated to about 5 ml using vacuum. Precipitate was filtered out and washed with cold methanol to obtain product 16 (151 mg, Y: 71 percent) as a pale yellow solid, which was already pure enough and was used directly in next step without further purification. 16: 1H NMR (DMSO-d6): delta 9.45 (IH, br), 7.80 (IH, b), 7.62 (IH, d, J= 8.8 Hz), 7.53 (4H, m), 6.93 (IH, d, A, J1 = 8.8 Hz, J2 = 2.0 Hz), 6.82 (3H, m), 5.35 (2H, b). HRMS (EI) m/z calcd. for [Ci6Hi3NO]+ 235.0097, found 235.0091. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 10h; | (1) The following reagents and solvents were put into a reaction container. 4,4'-dichlorodiphenyl sulfone: 10 g 4-hydroxyphenylboric acid: 5.8 g sodium hydrogen carbonate: 10 g dioxane: 400 ml water: 200 ml tetrakistriphenylphosphine palladium: 0.8 g Subsequently, the reaction solution was heated to 90 C. and agitation was performed at this temperature (90 C.) for 10 hours. At this time, the degree of proceeding of the reaction was ascertained with TLC appropriately. Then, the reaction was terminated with an ammonium chloride aqueous solution, and an organic phase was extracted with ethyl acetate. The resulting organic phase was washed with water and saturated saline solution in that order and was dried with anhydrous magnesium sulfate. A crude product obtained by concentrating the organic phase under reduced pressure was refined through column chromatography. The thus obtained product was used as-is in the following step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In methanol; water; toluene;Inert atmosphere; Reflux; | General procedure: To a solution of bromobiphenylaldehyde (6, 260 mg, 1 mmol) and various phenyl boronic acids (7a-j, 1 mmol) in 2 M aqueous sodium carbonate (2 mL) and toluene/ethanol (9:3 mL) is added a catalytic amount (0.4% mol) of tetrakis-triphenylphosphine palladium, and the mixture was reflux under argon atmosphere for 2-3 h. After completion of reaction, the suspension is cooled and extracted with ethyl acetate (3 × 30 mL) and the organic phase was washed with water and brine, dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure to get the crude product. This residue was further purified by column chromatography using ethyl acetate and hexane to afford the pure terphenylaldehydes (8). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With potassium carbonate; In water; N,N-dimethyl-formamide; at 100.0℃; for 3.0h; | A mixture of 3-cyano-4-trifluoromethyl- l -fluorobenzene (70 g, 0.37 mol, Oakwood), 4-hydroxyphenylboronic acid (50 g, 0.36 mol, Boron Molecular), K2C03 (70 g) and DMF/water (400 mL/40 mL) was heated to 100C for 3h. After cooling to RT, the mixture was diluted with water (1 L) and extracted with EtOAc (1.5 L). The organic layer was washed with water (0.5 L) and brine, concentrated and purified by chromatographed over silica gel with 4% MeOH in chloroform to give (4-(3-cyano-4-(trifluoromethyl)phenoxy)phenyl)boronic acid as pink solid (50 g, 45%). |
42% | With caesium carbonate; In N,N-dimethyl-formamide; at 100.0℃; for 4.0h; | A mixture of compound 27 (2.1 g, 10.9 mmol), compound 28 (2.4 g), and Cs2C03 (3.5 g, 10.9 mmol) in DMF (14 mL) was heated at 100C for 4 hours. After cooling to room temperature, the mixture was diluted with water (l OOmL) and extracted with EtOAc (3x100 mL). The combined organic layer was washed with brine, concentrated and purified by column chromatography (silica gel,EtOAc/hexanes 1/1 ) to give (4-(3-cyano-4-trifluoromethyl)phenoxy)phenyl)boronic acid (29) (pink solid, 42%). ? NMR (400MHz, CD3OD): 7.59 - 7.86 (3H, m), 7.31 - 7.37 ( 1 H, m), 7.19 - 7.26 (1 H, m), 6.9 - 7.10 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7-Bromo-1H-indene (250 mg, 1.28 mmol), 4-hydroxyphenylboronic acid (212 mg, 1.54 mmol), sodium carbonate (270 mg, 2.56 mmol), Pd(PPh3)4 (catalytic amount), 1,4-dioxane (10 mL), and water (3 mL) were added, and stirred at 90 C for 8 hours. The solvent was distilled away under reduced pressure. Ethyl acetate was used as an extraction solvent, and after washing with a 1 N hydrochloric acid aqueous solution and saturated brine, the resultant was dried over magnesium sulfate. The solvent was distilled away under reduced pressure. To half of the resulting residue, methanol (10 mL) and a catalytic amount of 10% palladium-carbon were added, and stirred in a hydrogen atmosphere at room temperature overnight. The insoluble material was filtered off, and the solvent was distilled away under reduced pressure. An operation similar to that in Step 2 of Example 9 was performed on the resulting residue to thus obtain the title compound. Yield: 3.1 mg (0.007 mmol) MS (ESI, m/z) 442 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; N,N-dimethyl-formamide; for 8h;Reflux; | A 250 mL of round-bottom flask was charged with 4-hydroxyphenylboronic acid (1.10 g, 8.0 mmol), <strong>[13667-12-4]1-bromo-4-phenylethynylbenzene</strong> (2) (1.80 g, 7.0 mmol), K2CO3 (4.40 g, 32.0 mmol), Pd(PPh3)4 (0.025 g, 0.021 mmol), DMF (50 mL), and water (10 mL). The mixture was heated to reflux and stirred for 8 h. Then the mixture was poured into a water solution of 10% K2CO3 (200 mL), and then the precipitate was filtered under reduced pressure as a gray solid. The obtained residue was purified by column chromatography on silica gel (petroleum ether as eluting agent) to give the corresponding pure cross-coupling product 4 as a white powder (1.42 g, 75%). m.p. = 228-230 C. 1H NMR (400 MHz, Acetone-d6): 8.56 (s, 1H), 7.67 (d, J = 8.3 Hz, 1H), 7.59 (dd, J = 13.3, 5.2 Hz, 6H), 7.49-7.37 (m, 3H), 6.97 (d, J = 8.6 Hz, 2H). 13C NMR (101 MHz, Acetone-d6): 141.88(1C), 132.81(2C), 132.29(2C), 132.10(1C), 129.48(2C), 129.32(2C), 128.88(2C), 127.17(2C), 124.19(1C), 121.92(1C), 116.65(1C), 116.72(1C), 90.36(1C), 90.13(1C). ESI-MS (m/z): calcd for C20H14O 270.1045, found 270.1048. |
75% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; N,N-dimethyl-formamide; for 8h;Reflux; | To a 250 ml three-necked flask was added 1.10 g (0.0080 mol) of 4-hydroxybenzeneboronic acid, 1.80 g (0.0070 mol) of 4- (2-phenylethynyl) -bromobenzene, 4.4 g (0.032 mol) of K2CO3, 50 ml of DMF, 10 ml of water and 0.025 g (0.000021 mol) of tetraphenylphosphine palladium catalyst were charged and heated to reflux for 8 hours.The reaction was poured into 200 ml of water and filtered to give a gray solid which was separated by column chromatography and eluted with petroleum ether to give a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,4-dioxane; water;Inert atmosphere; Reflux; | General procedure: To 0.329 g (1.5 mmol) 4-iodoaniline, 1.8 mmol ArB(OH)2, 0.318 g (3 mmol) Na2CO3 and 75 mg (0.075 mmol) PdCl2(PPh3)2, 15 mL of a blended solution of dioxane and water (v/v = 3/1) was added under N2 atmosphere. Then the reaction was heated to reflux and monitored by TLC. Upon cooling, the reaction mixture was dilute with sat. NH4Cl solution, then extracted with EA (3×20 mL), and the organic layer was washed with saturated NaCl aqueous solution, dried over anhydrous Na2SO4 and purified by flash chromatography to afford different 4-aminobiphenyl derivatives. According to the reductive amination procedure, the 4-aminobiphenyl derivative was further treated with salicylaldehyde and to afford the corresponding compound 5&6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; water; at 90℃; for 3h;Inert atmosphere; | In a 100mL three-necked flask, were added 4-hydroxyphenyl boronic acid (10.0g, 61.4mmol), 4- bromothiazole (10.2g, 73.7mmol), potassium carbonate (25.4g, 184.2mmol), 1,4- dioxane (30mmol), water (10mL) and bis triphenylphosphine palladium dichloride (2.15g, 3.07mmol). Under nitrogen, the reaction system was heated to 90 , stirred for 3h. Concentrated under reduced pressure to remove the solvent by distillation, the residue was dissolved in ethyl acetate (100 mL), saturated brine was added, extracted liquid separation. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product as a pale yellow oil, purified by column chromatography to give the title product as a beige solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With palladium diacetate; potassium carbonate; triphenylphosphine; In water; N,N-dimethyl-formamide; at 100℃; for 3h;Inert atmosphere; Sealed tube; Microwave irradiation; | <strong>[16870-28-3]2-hydroxy-4-iodobenzoic acid</strong> (50 mg, 0.189 mmol), 4-hydroxyphenylboronic acid (31.3 mg, 0.227 mmol), PPh3 (7.4 mg, 0.028 mmol), K2CO3 (91.4 mg, 0.662 mmol), Pd(AcO)2 (2.12 mg, 0.0095 mmol), 1:1 DMF: H2O (2 ml) were used. Purification was carried out by flash chromatography, eluting with an AcOEt: CH3CN:H2O:CH3OH mixture (gradient from 70:5:2.5:2.5 to 60:10:10:10). Compound 99 was obtained in the form of a solid. Yield after purification: 100 % (44 mg). 1H NMR (500 MHz, methanol-d4) delta 7.86 (d, J = 8.6 Hz, 1H), 7.48 (m, 2H), 7.07-7.05 (m, 2H), 6.89-6.85 (m, 2H). 13C NMR (126 MHz, methanol-d4) delta 174.5 (CO), 163.0 (C), 158.9 (C), 148.6 (C), 132.3 (C), 131.9 (CH), 129.2 (CH), 118.0 (CH), 116.6 (CH), 114.9 (CH), 113.8 (C). HRMS (TOF, ES-): Calculated for C13H9O4: (M-H)-: m/z 229.0501. 229.0510 found (deviation 3.9 ppm). m.p. (C) = 265.8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.5% | Use a vacuum pump to vacuum the reactor to -0.1Mpa, reduce the temperature of the reactor to 10, add 1.66kg (10mol) <strong>[22237-13-4]p-ethoxyphenylboronic acid</strong>, 1.57kg (20mol) acetyl chloride, 15L toluene into the reactor, and mix Stir until uniform, and then add 2mol aluminum chloride. During the reaction process, the temperature is increased by 10C every 15 minutes, until the temperature is increased to 80C, and then react at a constant temperature for 2h (the monochloroethane gas generated during the reaction is removed to the recovery system by vacuum ) To obtain the intermediate compound, add potassium carbonate solution to adjust the pH of the system to 9 to obtain an aqueous layer, continue to use sulfuric acid to adjust the aqueous layer to pH 3, extract with ethyl acetate, collect the organic layer, concentrate, and reweight with heptane Crystallized to obtain 1.29 kg of p-hydroxyphenylboronic acid, with a yield of 93.5% and a purity of 99.1%. |
Tags: 71597-85-8 synthesis path| 71597-85-8 SDS| 71597-85-8 COA| 71597-85-8 purity| 71597-85-8 application| 71597-85-8 NMR| 71597-85-8 COA| 71597-85-8 structure
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