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Yuan, Gengyang ; Dhaynaut, Maeva ; Lan, Yu ; Guehl, Nicolas J. ; Huynh, Dalena ; Iyengar, Suhasini M. , et al.
Abstract: Metabotropic glutamate receptor 2 (mGluR2) is a therapeutic target for several neuropsychiatric disorders. An mGluR2 function in etiology could be unveiled by positron emission tomography (PET). In this regard, 5-(2-fluoro-4-[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-7-carboxamide ([11C]13, [11C]mG2N001), a potent negative allosteric modulator (NAM), was developed to support this endeavor. [11C]13 was synthesized via the O-[11C]methylation of phenol 24 with a high molar activity of 212 ± 76 GBq/μmol (n = 5) and excellent radiochemical purity (>99%). PET imaging of [11C]13 in rats demonstrated its superior brain heterogeneity and reduced accumulation with pretreatment of mGluR2 NAMs, VU6001966 (9) and MNI-137 (26), the extent of which revealed a time-dependent drug effect of the blocking agents. In a nonhuman primate, [11C]13 selectively accumulated in mGluR2-rich regions and resulted in high-contrast brain images. Therefore, [11C]13 is a potential candidate for translational PET imaging of the mGluR2 function.
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Purchased from AmBeed: 16289-54-6 ; 5521-55-1 ; 22047-25-2 ; 98-80-6 ; 40155-47-3 ; 5720-05-8 ; 879-65-2 ; 98-96-4 ; 31519-62-7 ; 23688-89-3 ; 23611-75-8 ; 33332-25-1 ; 20737-42-2 ; 61442-38-4 ; 17933-03-8 ; 50681-25-9 ; 13924-99-7 ; 40155-43-9 ; 166744-78-1 ; 36070-80-1 ; 4595-61-3 ; 118853-60-4 ; 41110-28-5 ; 40155-42-8 ; 937669-80-2 ; 31462-59-6 ; 16419-60-6 ; 5424-01-1 ; 59-67-6 ; 34604-60-9 ; 27398-39-6 ; 1196151-53-7 ; 19847-12-2 ; 13965-03-2 ; 876161-05-6 ; 27825-21-4 ; 2164-61-6 ; 4604-72-2 ; 98-97-5 ; 24005-61-6 ; 5521-61-9 ; 2516-34-9 ; 2719-27-9 ; 123-90-0 ; 6761-50-8 ; 625-43-4 ; 872-64-0 ; 1309866-36-1 ; 36932-49-7 ; 1528085-68-8 ; 1195533-51-7 ; 13534-79-7
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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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Structure activity relationship of pyrazinoic acid analogs as potential antimycobacterial agents
Hegde, Pooja V. ; Aragaw, Wassihun W. ; Cole, Malcolm S. ; Jachak, Gorakhnath ; Ragunathan, Priya ; Sharma, Sachin , et al.
Abstract: Tuberculosis (TB) remains a leading cause of infectious disease-related mortality and morbidity. Pyrazinamide (PZA) is a critical component of the first-line TB treatment regimen because of its sterilizing activity against non-replicating Mycobacterium tuberculosis (Mtb), but its mechanism of action has remained enigmatic. PZA is a prodrug converted by pyrazinamidase encoded by pncA within Mtb to the active moiety, pyrazinoic acid (POA) and PZA resistance is caused by loss-of-function mutations to pyrazinamidase. We have recently shown that POA induces targeted protein degradation of the enzyme PanD, a crucial component of the CoA biosynthetic pathway essential in Mtb. Based on the newly identified mechanism of action of POA, along with the crystal structure of PanD bound to POA, we designed several POA analogs using structure for interpretation to improve potency and overcome PZA resistance. We prepared and tested ring and carboxylic acid bioisosteres as well as 3, 5, 6 substitutions on the ring to study the structure activity relationships of the POA scaffold. All the analogs were evaluated for their whole cell antimycobacterial activity, and a few representative mols. were evaluated for their binding affinity, towards PanD, through isothermal titration calorimetry. We report that analogs with ring and carboxylic acid bioisosteres did not significantly enhance the antimicrobial activity, whereas the alkylamino-group substitutions at the 3 and 5 position of POA were found to be up to 5 to 10-fold more potent than POA. Further development and mechanistic anal. of these analogs may lead to a next generation POA analog for treating TB.
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Keywords: Tuberculosis ; Pyrazinoic acid ; pyrazinamide
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Purchased from AmBeed: 16289-54-6 ; 5521-55-1 ; 22047-25-2 ; 98-80-6 ; 40155-47-3 ; 5720-05-8 ; 879-65-2 ; 98-96-4 ; 31519-62-7 ; 23688-89-3 ; 23611-75-8 ; 33332-25-1 ; 20737-42-2 ; 61442-38-4 ; 17933-03-8 ; 50681-25-9 ; 13924-99-7 ; 40155-43-9 ; 36070-80-1 ; 4595-61-3 ; 118853-60-4 ; 41110-28-5 ; 40155-42-8 ; 937669-80-2 ; 98-98-6 ; 31462-59-6 ; 16419-60-6 ; 5424-01-1 ; 59-67-6 ; 34604-60-9 ; 27398-39-6 ; 1196151-53-7 ; 19847-12-2 ; 13965-03-2 ; 876161-05-6 ; 27825-21-4 ; 2164-61-6 ; 4604-72-2 ; 98-97-5 ; 24005-61-6 ; 103-67-3 ; 5521-61-9 ; 2516-34-9 ; 2719-27-9 ; 123-90-0 ; 6761-50-8 ; 625-43-4 ; 872-64-0 ; 36932-49-7 ; 1528085-68-8 ; 1195533-51-7 ; 13534-79-7
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CAS No. : | 16419-60-6 |
Formula : | C7H9BO2 |
M.W : | 135.96 |
SMILES Code : | C1=CC=CC(=C1B(O)O)C |
MDL No. : | MFCD00093526 |
InChI Key : | NSJVYHOPHZMZPN-UHFFFAOYSA-N |
Pubchem ID : | 2733267 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
88% | With potassium fluoride; iodine; In 1,4-dioxane; at 80℃; for 1h; | General procedure: A mixture of the arylboronic acid (0.55mmol), KF (96mg, 1.65mmol) and I2 (127mg, 0.50mmol) in 1,4-dioxane (5mL) was stirred at 80C for 1h. Then it was filtered through silica gel, eluting with Et2O (10mL) and the solvent was removed by rotary evaporation. When necessary, the product was purified by chromatography on silica gel (petroleum ether/Et2O 98:2). |
75% | With 1,10-Phenanthroline; oxygen; potassium iodide; copper(ll) bromide; In N,N-dimethyl-formamide; at 80℃; for 20h; | General procedure: under oxygen, a sealed reaction tube was charged with KX (X = I, Br) (0.2 mmol), arylboronic acid (0.3 mmol), CuBr2 (4.5 mg, 10 mol %), 1,10-phen (7.2 mg, 20 mol %) and DMF (2 mL). The mixture was stirred at 80 or 130 C. After the completion of the reaction, the solvent was evaporated under reduced pressure and the residue was purified by flash column chromatography on silica gel to give the product. |
72% | With iodine; potassium carbonate; In acetonitrile; at 80℃; for 10h;Inert atmosphere; Schlenk technique; Sealed tube; | General procedure: Arylboronic acid 1 (0.5 mmol) and K2CO3 (1 mmol, 138.0mg) were added to a 20 mL Schlenk-tube equipped with amagnetic stir bar. The tube was evacuated twice and backfilledwith N2. MeCN (2 mL) and I2 (0.75 mmol, 191 mg)were added to the tube at r.t. under a stream of N2, and thetube was sealed and placed into a pre-heated oil bath at 80 Cfor 8-12 h. The resulting solution was cooled to r.t. and H2O(10 mL) was added. The aq layer was extracted with EtOAc (3 × 5 mL). For products 2s and 2t, HCl (1 M) was added tothe aq solution until pH 2 before extraction. The combinedorganic phase was dried over anhydrous Na2SO4, filteredand concentrated by rotary evaporation. Purification of theresidue by column chromatography on silica gel providedthe desired product 2a-v |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46%Chromat. | With potassium carbonate; In water; at 100℃; for 24h;Inert atmosphere; | General procedure: A mixture of aryl halide (0.5 mmol, 1.0 equiv.), phenylboronic acid (0.6 mmol, 1.2 equiv.), K2CO3 (2 mmol, 4equiv.), the Pd-NP-PIL catalyst (1.7 mol% based on the arylhalide substrate) in water (3 mL) was heated to 100 C under nitrogen with vigorous stirring for 4 h. The reaction mixture was then cooled at r.t. and the product was extracted with diethyl ether (3×3 mL). The combined extracts were washed with brine (15 mL), dried over anhydrous MgSO4, filtered and the solution was analyzed by GC. The structure of the products was also confirmed by 1H NMR spectroscopy. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step C: 2-[1-(3-Nitrophenyl)ethylamino]-4-[benzimidazol-1-yl]-6-(2-methylphenyl)pyrimidine The title compound was prepared from 2-[1-(3-nitrophenyl)ethylamino]-4-[benzimidazol-1-yl]-6-chloropyrimidine and 2-methylphenylboronic acid according to the precedure described in EXAMPLE 306, Step C and using [1,1'-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) as catalyst. Mass spectrum (CH3CN/TFA/NH4O2CH/ESI) 451.3 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With disodium hydrogenphosphate; disodium bis(2-aminopyrimidine-4,6-diolate)palladium acetate; In water; at 50 - 120℃; for 0.166667h;Microwave irradiation; | In a 35 mL microwave reaction vessel, commercially available 4-bromo-3- methylbenzoic acid (0.2 g, 0.93 mmol), o-tolylboronic acid (0.151 g, 1.12 mmol) and Na2HPO4 (0.66 g, 4.65 mmol) were sequentially added. H20 (6.0 mL) was added and the mixture stirred at 50 C to dissolve most of the materials. Bis-(disodium 2-aminopyrimidine-4,6-diolate) palladium acetate [prepared as described in I Am. Chem. Soc. 2009, 131, 16346-1 6347] (0.01 M in Pd(II),1.50 mL, 0.0 15 mmol) was added to the reaction and the tube was heated to 120 C under microwave irradiation for 10 mm, under vigorous stirring. After cooling to r.t., the reaction was partitioned between 1.0 M HC1 solution (100 mL) and EtOAc (100 mL). The organic layer was separated, dried over Na2504, filtered and concentrated affording a solid residue (0.304 g). Purification by typical silica gel flash chromatography (CH2C12) afforded the pure titlecompound (0. 20 g, 95%) as a white wax. R= 2.20 mm. MS (ESI) m/z: 225 [M-Hf. ?H NMR (DMSO-d6): oe 12.90 (s, 1H), 7.90 (d, 1H, J= 1.0 hz), 7.80 (dd, 1H, J= 7.9, 1.6 Hz), 7.35-7.23 (m, 3H), 7.19 (d, 1H, J= 7.9 Hz), 7.07 (dd, 1H, J= 7.5, 1.4 Hz), 2.04 (s, 3H), 1.99 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84.8% | With potassium carbonate; triphenylphosphine;palladium diacetate; In 1,2-dimethoxyethane; ethyl acetate; | Step 1: Synthesis of 2-amino-2'-methyl-biphenyl Added together 2-methylphenyl boronic acid (24.7 g, 181 mmol), 2-bromo aniline (25.7 g, 151 mmol), palladium(II)acetate (0.85 g, 3.78 mmol), triphenylphosphine (4.0 g, 15.1 mmol), a 2 M solution of potassium carbonate (204 mL) and ethylene glycol dimethyl ether (223 mL) and heated the reaction mixture at reflux for 18 hours. After the reaction was cooled to room temperature, the aqueous phase was separated from the organic phase. The aqueous phase was extracted with ethyl acetate and the organic extractions were combined, dried over magnesium sulfate and filtered. The crude product was purified by silica gel column chromatography using 10% ethyl acetate in hexanes as the eluants. The pure fractions were collected, combined and concentrated to give 2-amino-2'-methyl-biphenyl (23.5 g, 84.8% yield) whose structure was confirmed by GCMS and NMR. |
84.8% | With palladium diacetate; potassium carbonate; triphenylphosphine; In 1,2-dimethoxyethane; for 18h;Reflux; | Step 1: Synthesis of 2-amino-2?-methyl-biphenyl Added together 2-methylphenyl boronic acid (24.7 g, 181 mmol), 2-bromo aniline (25.7 g, 151 mmol), palladium(II)acetate (0.85 g, 3.78 mmol), triphenylphosphine (4.0 g, 15.1 mmol), a 2 M solution of potassium carbonate (204 mL) and ethylene glycol dimethyl ether (223 mL) and heated the reaction mixture at reflux for 18 hours. After the reaction was cooled to room temperature, the aqueous phase was separated from the organic phase. The aqueous phase was extracted with ethyl acetate and the organic extractions were combined, dried over magnesium sulfate and filtered. The crude product was purified by silica gel column chromatography using 10% ethyl acetate in hexanes as the eluants. The pure fractions were collected, combined and concentrated to give 2-amino-2?-methyl-biphenyl (23.5 g, 84.8% yield) whose structure was confirmed by GCMS and NMR. |
84.8% | With palladium diacetate; potassium carbonate; triphenylphosphine; In 1,2-dimethoxyethane; for 18h;Reflux; | Step 1: Synthesis of 2-Amino-2'-methyl-biphenyl 2-methylphenyl boronic acid (24.7 g, 181 mmol), 2-bromoaniline (25.7 g, 151 mmol), palladium (II) acetate (0.85 g, 3.78 mmol), triphenylphosphine (4.0 g, 15.1 mmol) and added to a 2 M solution of potassium carbonate (204 ) and ethylene glycol dimethyl ether (223) together, and the reaction mixture was heated to reflux for 18 hours. After cooling the reaction to room temperature and separating the aqueous phase from the organic phase. The aqueous phase was extracted with ethyl acetate, the organic extracts were combined, dried over magnesium sulfate, and filtered. And the crude product was used as an eluent of 10% ethyl acetate in hexane was purified by silica gel column chromatography. The pure fractions were combined and collected, and concentrated to which 2-amino-2'-methyl-biphenyl-gain (23.5 g, 84.8% yield), its structure was confirmed by GCMS and NMR. |
62% | With C20H12N2O8PdS2(2-)*2Na(1+); sodium hydroxide; In water; at 100℃; for 3h; | General procedure: A solution of aryl bromide (0.5 mmol), arylboronic acid (0.75 mmol), NaOH (1.0 mmol), and complex 1 (0.5 mol %) in H2O (1.0 mL) was stirred at 100 C for 5 h. The reaction mixture was quenched with water (10 mL) and extracted with EtOAc (3 × 10 mL). The combined EtOAc extracts were dried over anhydrous Na2SO4, filtrated, and then the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel with PE or PE/EtOAc as the eluent to obtain the desired products. |
29.5% | With Supported Pd(OAc)2(PPh3)2 Over Mixed Magnesium Hydroxide and Cerium Carbonate Hydroxide Composite; In water; at 79.84℃; for 2h; | General procedure: A typical procedure for Suzuki reaction is as follows: arylhalide (0.5mmol) was weighed in 25mL round bottom flask containing boronic acids (0.6mmol), and Pd(OAc)2(PPh3)2/MgCe-HDC (100mg). The reactants and catalyst were dispersed in water (4mL), the RB was mounted on an oil bath at 353K and the mixture was stirred for 2h. The reaction was monitored by thin layer chromatography (TLC). After completion of the reaction, the catalyst was separated by filtration. Then the solution was extracted with ethyl acetate and brine solution. The organic phase was dried over anhydrous Na2SO4 and concentrated under vacuum. The crude product was purified by column chromatography on silicagel to afford pure product. The pure product was analyzed using 1H- and 13C-NMR techniques and compared with literature NMR data. |
With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In ethanol; water; toluene; at 100℃; for 16h; | To a 100mL round bottom flask equipped with a magnetic stir bar, o-tolylboronic acid (15mmol, 1.5equiv), K2CO3 (5.520g, 40mmol, 4.0equiv), and Pd(PPh3)4 (1154mg, 1.000mmol, 0.1equiv) were dissolved in 45mL toluene followed by the addition of 9mL of H2O and 15mL of EtOH. Then 2-bromoaniline (10mmol, 1.0equiv) was added and the resulting mixture was stirred at 100C for 16h. After cooling to room temperature, the biphasic solution was diluted with 50mL of saturated aqueous NH4Cl, and 30mL of CH2Cl2. The aqueous phase was extracted with diethyl ether (3×30mL) and the combined organic layers were washed with brine (40mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by flash column chromatography with ethyl acetate (EA) and petroleum ether (Pet) as eluent to afford the corresponding 2?-methylbiphenyl-2-amine (1p). 1H NMR (400MHz, CDCl3, TMS) delta 7.16-7.28 (m, 5H), 7.01 (d, J=7.2Hz, 1H), 6.80 (t, J=7.4Hz, 1H), 6.76 (d, J=7.6Hz, 1H), 3.44 (br s, 2H), 2.17 (s, 3H); 13C NMR (100MHz, CDCl3, TMS) delta 143.5, 138.6, 136.9, 130.2, 130.0, 130.0, 128.3, 127.7, 127.4, 126.1, 118.2, 115.0, 19.6. | |
With palladium diacetate; tricyclohexylphosphine; In water; toluene; at 100℃; for 6h; | General procedure: Reagents and conditions: (i) Pd(OAc)2, PCy3, Toluene, 0, 100C, 6h; (general yields 10-40%) | |
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 80℃; for 6h;Inert atmosphere; Schlenk technique; | General procedure: Taking 1d as an example: (A) Under a nitrogen atmosphere, a 100 mL Schlenk flask was charged with 2-bromoaniline (0.86 g, 5.0 mmol), 4-tert-butylphenylboronic acid (1.07 g, 6.0 mmol), Na2CO3 (1.33 g, 12.5 mmol), and a solvent mixture of toluene/EtOH/H2O (24 mL, 1:1:1 (v/v/v)) with stirring. Pd(PPh3)4 (0.29 g, 0.25 mmol) was added. Then, the mixture was stirred at 80 C for 6 h, cooled to room temperature, quenched with saturated NH4Cl, and extracted with EtOAc (3 × 25 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated to dryness under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of petroleum ether and ethyl acetate (10:1 (v/v)) as eluents to afford 4'-(tert-butyl)-[1,1'-biphenyl]-2-amine as a yellow oil (0.88 g, 78%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In butan-1-ol; at 55℃;Inert atmosphere; | Step 1 : To a solution of <strong>[791626-58-9]6-bromoquinolin-2-amine</strong> (5.0 g, 22 mmol), o-tolylboronic acid (4.3 g, 31 mmol), saturated sodium carbonate (2.5 ml, 22 mmol) and «BuOH (50 ml, 546 mmol) under N2 was added dichlorobis (triphenyl-phosphine)palladium (II) (1.6 g, 2.2 mmol). The reaction mixture was heated to 55 C and allowed to stir overnight. The reaction mixture was allowed to cool to RT then was extracted with EtOAc and washed with water and brine (3 x) then dried over MgS0 and concentrated in vacuo to remove solvent. The crude orange solid was dissolved in DCM and loaded onto achromatography column and eluted with 0-75% EtOAc/Hexane then 100% EtOAc to give 6-o-tolylquinolin-2-amine as light yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76.92% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; for 12h;Reflux; Inert atmosphere; | A mixture of o-tolyl boronic acid (760mg, 5.58mmol), 11 (1.5g, 5.08mmol), K2CO3 (1.05g, 7.66mmol), Pd(PPh3)4 (295mg) and H2O (3.8mL) in THF (30mL) was heated to reflux under N2 atmosphere for 12h. After the mixture was cooled to room temperature, filtered, the crude solid product 12 was purified by recrystallization with ethyl acetate. (1.2g, 76.92% yield). m.p. 208-209C; 1H NMR (400MHz, DMSO-d6): δ 12.59 (s, 1H), 8.60 (s, 1H), 8.06 (s, 1H), 7.71 (s, 2H), 7.22-7.37 (m, 4H), 4.23 (q, 2H, J=7.2Hz), 2.26 (s, 3H), 1.29 (t, 3H, J=7.2Hz); HRMS (ESI) for C19H17NO3: calcd. 308.12812 (M+H)+, found: 308.12776 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With dichlorobis(triphenylphosphine)palladium[II]; In 1,2-dimethoxyethane; | (1) Synthesis of 4-(2-methylphenyl)indene 38 g (180 mmol) of tripotassium phosphate, 100 mL of distilled water, 100 mL of DME, 10 g (73.6 mmol) of 2-methylphenylboronic acid, 12.0 g (61.5 mmol) of <strong>[16657-07-1]7-bromo-1H-indene</strong>, 1.00 g (1.42 mmol) of dichlorobis(triphenylphosphine)palladium, and 1.30 g (4.96 mmol) of triphenyl phosphine were put into a 500-mL glass reactor in that order, and then heated under reflux at 90 C. for 11 hours. This was left cooled to room temperature, then the reaction liquid was poured into 100 mL of distilled water, transferred into a separatory funnel, and extracted three times with hexane. At room temperature 6 mL of concentrated hydrochloric acid was added to the hexane solution, then stirred at room temperature for 30 minutes, the palladium compound was precipitated, filtered out through filter paper, and the filtrate was washed three times each with saturated saline water and distilled water, and dried with sodium sulfate. Sodium sulfate was filtered away, the solvent was evaporated away under reduced pressure, and the residue was purified through silica gel column chromatography (developing solvent, hexane/diisopropyl ether=20/1) to give 12.7 g (yield 100%) of 4-(2-methylphenyl)indene as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate; triphenylphosphine; In 1,2-dimethoxyethane; water; at 90℃; for 11h; | 38 g (180 mmol) of tripotassium phosphate, 100 mL of distilled water, 100 mL of DME, 10 g (73.6 mmol) of 2-methylphenylboronic acid, 12.0 g (61.5 mmol) of <strong>[16657-07-1]7-bromo-1H-indene</strong>, 1.00 g (1.42 mmol) of dichlorobis(triphenylphosphine)palladium, and 1.30 g (4.96 mmol) of triphenyl phosphine were put into a 500-mL glass reactor in that order, and then heated under reflux at 90 C. for 11 hours. This was left cooled to room temperature, then the reaction liquid was poured into 100 mL of distilled water, transferred into a separatory funnel, and extracted three times with hexane. At room temperature 6 mL of concentrated hydrochloric acid was added to the hexane solution, then stirred at room temperature for 30 minutes, the palladium compound was precipitated, filtered out through filter paper, and the filtrate was washed three times each with saturated saline water and distilled water, and dried with sodium sulfate. Sodium sulfate was filtered away, the solvent was evaporated away under reduced pressure, and the residue was purified through silica gel column chromatography (developing solvent, hexane/diisopropyl ether=20/1) to give 12.7 g (yield 100%) of 4-(2-methylphenyl)indene as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; In ethanol; water; toluene; at 90℃; for 12h;Inert atmosphere; Schlenk technique; Sealed tube; | General procedure: An oven-dried Schlenk flask containing a magnetic stir bar was charged with the appropriateboronic acid (1.5 equiv), Pd2dba3 (2.0 mol%), S-Phos (8.0 mol%) and anhydrous K2CO3 (4.0equiv). The Schlenk flask was capped with a rubber septum and then evacuated and backfilledwith argon (this sequence was repeated three times). 2-Bromo anilines (1.0 equiv) intoluene/EtOH/H2O (8: 2: 2, 0.25 M) was added through the septum via syringe and the Schlenkflask was sealed. The reaction was stirred at 90 C for 12 h under argon atmosphere beforebeing allowed to cool to room temperature. The mixture was extracted with ethyl acetate, andthe combined organic layers were washed with H2O and brine, dried over anhydrous MgSO4,concentrated by rotary evaporation. The crude material was purified by flash chromatographyon silica gel to give the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | General procedure: To a microwave vial was added N-Boc-2-amino-5-bromo-thiazole (0.09 mmol, 1 equiv.) followed by the boronic acid (0.27 mmol, 3 equiv.), Pd(PPh3)2C12 (0.005 mmol, 0.05 equiv.), aq. Cs2CO3 (4M, 0.36 mmol, 4 equiv.) and DME/EtOH/water 7:2:3 (1 mL). The reaction mixture was de-gassed with nitrogen for 2 mm and irradiated in a microwave at 130 C for 8 mi LC-MS analysis showed that the Boc group had been removed during the reaction. The reaction mixture was passed through 1 g Si-Thiol cartridges, eluting with EtOH. The filtrate was evaporated to dryness, purified by preparative LC-MS and isolated directly as the amine for use in Routes A, D (Fig. 9). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.544 g | With potassium carbonate; bis(dibenzylideneacetone)-palladium(0); 1,3,5,7-tetramethyl-8-phenyl-2,4,6-trioxa-8-phosphatricyclo[3.3.1.13,7]decane; In tetrahydrofuran; water; at 75℃; for 15h;Sealed tube; | To a solution of 245 <strong>[16657-07-1]7-bromoindene</strong> (4.182 g, 21.44 mmol) and 327 o-tolylboronic acid (3.496 g, 25.71 mmol, 1.20 eq) in 81 tetrahydrofuran (20 mL), 249 potassium carbonate (6.633 g, 47.30 mmol, 2.21 eq) was added. Then a solution of 313 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane (0.188 g, 0.64 mmol, 0.03 eq) and 314 bis(dibenzylideneacetone)palladium (0.124 g, 0.22 mmol, 0.01 eq) in tetrahydrofuran (20 mL) was added. Then 247 water (8 mL) was added. The reaction vessel was sealed. The reaction was stirred and heated to 75 C. in a sealed vessel for 15 h. The reaction was allowed to cool to room temperature. The reaction was then concentrated in vacuo. The residue underwent aqueous extraction with hexane (4×50 mL). The combined hexane extracts were washed with saturated, aqueous potassium carbonate (100 mL) and then brine (100 mL). The washed hexane extracts were dried with anhydrous magnesium sulfate and filtered. The dried filtrate was concentrated in vacuo. The crude material was purified by silica gel column chromatography with isohexane eluent to afford the 328 product as a clear, colorless oil which may begin to solidify around room temperature (2.544 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.4 mg | With copper diacetate; triethylamine; In dichloromethane; at 20℃; for 16.0h;Inert atmosphere; | 2-methylphenylboronic acid (500.0 mg, 3.7 mmol, 1.0 equiv.) was dissolved in DCM (15 mL), then tert-butyl N-[8-azabicyclo[3.2.1]octan-3-yl]carbamate (832.3 mg, 3.7 mmol, 1.0 equiv.), Cu(OAc)2 (133.6 mg, 0.7 mmol, 0.2 equiv.) and TEA (1.0 mL, 7.4 mmol, 2.0 equiv.) were added under an atmosphere of nitrogen. The reaction mixture was stirred for 16 hours at ambient temperature then quenched by the addition of water. The resulting mixture was extracted with ethyl acetate, washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate/petroleum ether (1:5) to give tert-butyl N-[8-(2- methylphenyl)-8-azabicyclo[3.2.1]octan-3-yl]carbamate (82.4 mg) as a colorless oil. LCMS Method CA: [M+H]+ = 317. |
Tags: 2-Tolylboronic acid | Benzene Compounds | Organoboron | Aryls | Boronic Acids | Organic Building Blocks | Boronic Acids/Esters | Organometallic Reagents | 16419-60-6
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