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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.
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Rajapaksha, Ishanka N. ; Wang, Jing ; Leszczynski, Jerzy ; Scott, Colleen N. ;
Abstract: NIR dyes have become popular for many applications, including biosensing and imaging. For this reason, the mol. switch mechanism of the xanthene dyes makes them useful for in vivo detection and imaging of bioanalytes. Our group has been designing NIR xanthene-based dyes by the donor-acceptor-donor approach; however, the equilibrium between their opened and closed forms varies depending on the donors and spacer. We synthesized donor-acceptor-donor NIR xanthene-based dyes with an alkyne spacer via the Sonogashira coupling reaction to investigate the effects of the alkyne spacer and the donors on the maximum absorption wavelength and the mol. switching (ring opening) process of the dyes. We evaluated the strength and nature of the donors and the presence and absence of the alkyne spacer on the properties of the dyes. It was shown that the alkyne spacer extended the conjugation of the dyes, leading to absorption wavelengths of longer values compared with the dyes without the alkyne group. In addition, strong charge transfer donors shifted the absorption wavelength towards the NIR region, while donors with strong π-donation resulted in xanthene dyes with a smaller equilibrium constant DFT/TDDFT calculations corroborated the exptl. data in most of the cases. Dye 2 containing the N,N-dimethylaniline group gave contrary results and is being further investigated.
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Keywords: donor-acceptor-donor ; NIR dyes ; xanthene dyes ; amine donors ; alkyne spacers
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Purchased from AmBeed: 589-87-7 ; 768-60-5 ; 201802-67-7 ; 262861-81-4 ; 57102-42-8 ; 17573-94-3 ; 1066-54-2 ; 205877-26-5 ; 28611-39-4 ; 1195931-66-8
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Krzysztof Kuciński ; Grzegorz Hreczycho ;
Abstract: Commercially available and inexpensive potassium bis(trimethylsilyl)amide (KHMDS) serves as an efficient transition metal-free catalyst for the catalytic sp C−H silylation of several terminal alkynes including two pharmaceuticals. Overall, the presented system allows the synthesis of various attractive silylacetylenes under mild conditions, making this approach an environmentally benign and sustainable alternative to existing synthetic solutions.
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Purchased from AmBeed: 768-60-5 ; 40307-11-7 ; 171290-52-1 ; 766-83-6 ; 886363-40-2 ; 62452-73-7 ; 1945-84-2 ; 29079-00-3 ; 766-97-2 ; 705-31-7 ; 23152-99-0 ; 14630-40-1 ; 766-47-2 ; 873-73-4 ; 2510-23-8 ; 704-41-6 ; 67237-53-0 ; 160542-02-9 ; 766-49-4 ; 769-26-6
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CAS No. : | 768-60-5 |
Formula : | C9H8O |
M.W : | 132.16 |
SMILES Code : | C1=C(C=CC(=C1)C#C)OC |
MDL No. : | MFCD00168815 |
InChI Key : | KBIAVTUACPKPFJ-UHFFFAOYSA-N |
Pubchem ID : | 251020 |
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 |
---|---|---|
93% | General procedure: 2-iodoaniline (500.2 mg, 2.28 mmol, 1.0 equiv) was dissolved in Et3N (4.5 mL). The resulting solution was added with PdCl2(PPh3)2 (32.1 mg, 0.046 mol, 0.02 equiv) and CuI (17.4 mg, 0.091mmol, 0.04 equiv). The orange-yellow solution was degassed by bubbling with a stream of argon into the solution at room temperature for 30 min. After degassing, phenylacetylene (0.30 mL,279.0 mg, 2.73 mmol, 1.2 equiv) was added as a neat liquid into the solution via syringe. The resulting dark brown solution was allowed to stir at room temperature under argon atmosphere overnight. The reaction was quenched by addition of sat. aq. NH4Cl. The separated aqueousphase was extracted with EtOAc (3x times). The combined organic phases were washed with sat. aq. NaCl, dried over anh. Na2SO4, filtered and concentrated to a crude product. The crudeproduct was purified by SiO2 column chromatography eluting with 0-10% EtOAc-hexane to give 398.2 mg (90%) of 2-(phenylethynyl)aniline as an orange solid. | |
75% | With sodium hydroxide; In toluene; at 130℃; for 72h; | General procedure: To a stirred solution of the corresponding 2-iodoaniline (6, 1 mmol) in toluene (3 mL) under argon atmosphere were added Pd/CuO-Fe3O4 (50 mg), NaOH (400 mg, 10 mmol), and the corresponding alkyne (2, 1.5 mmol). The resulting mixture was stirred at 130 C until the end of reaction (see Table 6). The catalyst was removed by a magnet and the resulting mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to remove the solvent. The product was purified by chromatography on silica gel (hexane/ethyl acetate) to give the corresponding compounds 7. Yields are included in Table 6. Then, to a stirred solution of 7 (1 mmol) in toluene (4 mL) was added ZnBr2 (225 mg, 1 mmol). The resulting mixture was stirred at 130 C during 24 h. The mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to give the pure products 8 in quantitative yields. Physical and spectroscopic data for compounds 7 and 8, as well as literature for known compounds, follow. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
183 mg | With piperidine; bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 80℃; for 3h;Inert atmosphere; | General procedure: To a solution of 2-disubstituted 1-methyl-1H-imidazole 1 (1 mmol) in DMF (5 mL), NBS(169 mg, 0,95 mmol) was added and the resulting reaction mixture was stirred in the dark at room temperature for 3h. Then, Pd(PPh3)2Cl2 (14 mg, 0.02 mmol, 2 mol%), CuI (8 mg, 0.04mmol, 4 mol%), an alkyne 3 (1,1 mmol) and piperidine (300 muL, 255 mg, 3 mmol) were added and the resulting reaction mixture was stirred at 80C (when trimethylsilylacetylene was employed as the alkyne, the reaction was carried out at 50C) for 3 h. The reaction mixture was diluted with EtOAc (100 mL), then saturated aqueous NH4Cl (100 mL) was added. The resulting mixture was stirred for 30 minutes and extracted with EtOAc (3x 25mL). The organic extracts were washed with water (3 x 25 mL) and brine (1 x 25 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | General procedure: 4-Bromo-3-cyanopyridine 27 (92 mg, 0.5 mmol) in THF (5 mL)was added to CuI (9.6 mg, 50 lmol), (Ph3P)4Pd (29 mg, 25 lmol)and Na ascorbate (9.9 mg, 50 lmol) in Et3N (5 mL) under Ar. Themixture was stirred at 40 C for 30 min. Phenylethyne 21a(76.5 mg, 0.75 mmol) was added and the mixture was stirred at40 C for 10 h. Evaporation and chromatography (petroleumether/EtOAc 3:1) gave 28a (80 mg, 78%) as an off-white powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42%; 12% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In toluene; at 20℃; for 18h; | According to general procedure N2, cmpd 3 (284.8 mg, 0.417 mmol), pmethoxyphenylacetylene(48.4 mg, 0.366 mmol, 0.88 equiv), [PdCl2(PPh3)2](8.7 mg, 3.0 mol%) and CuI (2.1 mg, 2.6 mol%) were stirred in a solution oftoluene (100 mL) and Et3N (10 mL) at rt for 18 h. The reaction medium was evaporated to dryness andpurified by column chromatography (SiO2, using a gradient of eluent EtOAc/petroleum ether/CH2Cl2(4/95/1 to 0/0/100). The desired mono-coupled product was obtained as a purple solid (111.5 mg, 42%),while the bis-coupled was obtained as a blue solid (40.2 mg, 12%) and a part of starting material (113.7 mg,40%) was recovered. Mono-coupled product |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64.5% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 50 - 80℃;Inert atmosphere; | <strong>[1147-23-5]5-<strong>[1147-23-5]iodocytidine</strong></strong> (0.48 g, 2 mol) was added to 100 ml of the reaction tube under nitrogen atmosphere,4-methoxyphenylacetylene (0.40 g, 3 mol),Bis triphenylphosphine palladium dichloride(0.03 g, 0.1 mmol), Cuprous iodide (0.03 g, 0.12 mmol),40 ml of triethylamine and 10 ml of N, N-dimethylformamide,and reacted at 50 to 80 C for 6 to 10 hours. The solvent was removed in vacuo,add 30 ml of methanol to dilute, remove the insoluble solid by filtration, add silica gel and remove the solvent by rotary evaporation, and then methanol / dichloromethane mixed solvent column nucleoside derivative 1 (yellow solid) 310g, the yield was 64.5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; for 10h;Inert atmosphere; | (1)To <strong>[34883-46-0]1-iodo-2-phenoxybenzene</strong> (2g, 6.8mmol)Triethylamine (20mL)Adding 4 methoxyphenylacetylene to the solution(0.98 g, 7.4 mmol), Pd(PPh3)2Cl2 (95 mg, 135 mumol), CuI (26 mg, 135 mumol).Under argon protection conditions,After the reaction was carried out for 10 h, triethylamine was removed under reduced pressure.The residue was extracted with ethyl acetate (20 mL×3) then water (10 mL)Wash twice with saturated brine (10 mL), dry over anhydrous sodium sulfate and filtered.The solvent was removed under pressure. The residue was purified by silica gel column chromatography eluting elut1-((4-Methoxyphenyl)ethynyl)-2-phenoxybenzene(1.7 g, 85% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium fluoride; sodium azide; silver carbonate; In N,N-dimethyl-formamide; at 50℃; for 6.0h; | General procedure: to a solution of phenylacetylene (1a)(0.055 mL, 0.5 mmol), 2,6-di-tert-butyl-4-methylphenol(BHT) (2a) (133 mg, 0.6 mmol), NaN3 (39 mg, 0.6 mmol)and KF (58 mg, 1.0 mmol) in DMF (1 mL) at 50 C, Ag2CO3(41 mg, 0.15 mmol) was added. The reaction mixture wasthen stirred for 6 h when TLC conformed that substrate 1a was consumed. The resulting reaction mixture was cooled toroom temperature and extracted by dichloromethane(3×15 mL). The organic layer was washed with brine(3×40 mL), dried over MgSO4 and concentrated. Purificationof the crude product via flash column chromatography (silicagel; petroleum ether) and concentratinon in vacuo affordedthe desired product of 3a-N2/3a-N1 in 91% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine; In tetrahydrofuran; at 70℃; under 7.50075e-05 Torr; for 10h;Inert atmosphere; | In this embodiment, a white light emitting material is synthesized, and the chemical structure formula of the white light emitting material is as follows:The preparation method includes the following steps:(1) 5.0 mmol of tris (4-iodophenyl) amine, 21.0 mmol of 4-methoxyphenylacetylene, 30.0 mL of tetrahydrofuran,7.0mL of triethylamine was placed in a 100mL double-necked flask equipped with a stir bar and connected to a reflux tube;(2) The above reaction mixture is evacuated with a vacuum pump so that the pressure reaches 1x10-2Pa, and then nitrogen is passed in,Repeat the evacuation and nitrogen flow three times to maintain the nitrogen atmosphere of the reaction system;(3) adding 0.125 mmol of tetra (triphenylphosphine) palladium and 0.8 mmol of cuprous iodide to the above reaction solution under a nitrogen environment;(4) The above reaction mixture was heated to 70 C. under the protection of nitrogen and kept at reflux for 10 hours.The solvent was then evaporated to dryness on a rotary evaporator and washed with a small amount of ethyl acetate to give a yellow powder.Purified by column chromatography (silica gel column model: Yantai Jiangyou F-254 200-300 mesh,The mobile phase is a mixed solvent of methylene chloride and n-hexane, and the volume ratio of methylene chloride to n-hexane is 1:30).A white solid powder was obtained, that is, the white light-emitting material.The obtained white solid powder was characterized by carbon spectrum and proton spectrum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | General procedure: A mixture of <strong>[148231-12-3]5,8-dibromoquinoxaline</strong> (3) (287 mg, 1.0 mmol), Pd(PPh3)2Cl2 (70 mg, 0.1 mmol), CuI (9.5 mg, 0.05 mmol) and PPh3 (26 mg, 0.1 mmol) in triethylamine/tetrahydrofuran 1:1 (20 mL) was stirred and heating until 70 C. Then, the respective terminal arylacetylene (4aeg) (2.5 mmol) dissolved in tetrahydrofuran (10 mL) was added dropwise. The reaction mixture was stirred under reflux for 20min under a nitrogen atmosphere. Cooled down to room temperature, the solution was evaporated, and the crude product was purified by a silica gel chromatography column using hexane/dichloromethane (70:30) as the eluent to afford the respective final compound 5a-g. 5.3.1. 5,8-Bis[(4-methoxyphenyl)ethynyl]quinoxaline: compound 5a Yield: 74 mg (55%). IR (KBr): 2956, 2919, 2850, 2210, 1602, 1565, 1507, 1464, 1248, 826 cm 1.1H NMR (400 MHz, CDCl3) d ppm: 9.00 (s, 2 H), 7.97 (s, 2 H), 7.64 (d, J ¼ 8.0 Hz, AreH, 4 H), 6.93 (d, J ¼ 8.0 Hz, AreH, 4 H), 3.85 (s, -OCH3, 6 H). 13C NMR (100 MHz, CDCl3) d ppm: 160.1, 145.4, 143.1, 133.6, 133.4, 123.9, 115.0, 114.0, 97.8, 85.1, 55.3. APPI-MS m/z: Molecular formula C26H18N2O2 requires [MthH]th 391.1441; found: 391.1443. |