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CAS No. : | 14235-81-5 |
Formula : | C8H7N |
M.W : | 117.15 |
SMILES Code : | NC1=CC=C(C#C)C=C1 |
MDL No. : | MFCD00168824 |
InChI Key : | JXYITCJMBRETQX-UHFFFAOYSA-N |
Pubchem ID : | 3760025 |
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 |
---|---|---|
63% | With N,N,N',N'-tetramethylguanidine;copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In DMF (N,N-dimethyl-formamide); at 60℃; for 2.5h; | A mixture of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (1.10 g), 4-ethynylaniline (0.82 g), 1,1, 3,3- tetramethylguanidine (0.81 g), and copper (I) iodide (9.5 mg) in dry DMF (3.0 mL) was stirred and degassed with nitrogen. Tetrakis (triphenylphosphine) palladium (0) (115 mg) was added and the mixture heated at 60 C for 2.5 hours. The solvent was evaporated and the residue was triturated with DCM. The solid formed was filtered off and washed with water then dissolved in 1: 1 DCM/MeOH, filtered then evaporated. The solid obtained was triturated with ether and dried to give the title compound (0.67 g, 63%) ; 'HNMR (DMSO-d6) 5.50 (s, 2H), 6.55 (d, 2H), 6.95 (s, 2H), 7.15 (d, 2H), 8.35 (s, 2H) ; MS m/e MH+ 211. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Triphenylphosphine (30 mg, 115 pmol), [Pd(PPh3)2]C12 (20 mg, 285 pmol) and copper(l)iodide (16 mg, 84 pmol) were placed in a 100 ml three-necked flask and suspended in 30 ml methanol., or alternatively triphenylphosphine (30 mg, 115 pmol), [Pd(PPh3)2]C12 (20 mg, 285 pmol) and copper(l)iodide (16 mg, 84 pmol) were suspended in 30 ml methanol in a nitrogen flushed 100 ml three-necked flask. The trifluoroacetyl-5/6- aminochlorophenanthroline 4 (205 mg, 466 pmol) was transferred into the flask dissolved in20 ml methanol, in other words the educt trifluoroacetyl-5/6-aminochlorophenanthroline 4 (205 mg, 466 pmol) was transferred into the flask with 20 ml methanol. The reaction mixture was tempered or heated up to 40 00, or alternatively the reaction mixture was tempered or heated up to 4000, and nitrogen was fed into. Ethinylaniline (200 mg, 1.7 mmol) was dissolved in a few millilitres of methanol and added to the reaction mixture. Then, DIPEA(N,N-diisopropylethylamine, 2 ml) was added, and the reaction mixture was stirred overnight. After this, the reaction mixture was extracted three times with 50 ml chloroform, respectively. The chloroform phase was washed with a diluted sodium bicarbonate solution, diluted hydrochloric acid and again with a sodium bicarbonate solution. Then, the chloroform phase was dried over Na2SO4 and purified on an aluminium oxide column (eluent:chloroform). | ||
Example 1: Syntheis of the amino-reactive phosphorescent dye of the invention Nitration of <strong>[7089-68-1]2-chloro-1,10-phenanthroline</strong> 150 ml concentrated sulphuric acid was placed in a 500 ml three-necked flask and <strong>[7089-68-1]2-Chloro-1,10-phenanthroline</strong> 1 (CAS-Nr. 7089-68-1)(30g) was added while cooled with ice and stirred. The solution was heated in an oil bath to 180 °C. At 80 °C, the solution boiled and a strong smoke emission could be observed. At 160 °C, nitric acid (65 percent, 80 ml) was added dropwise while maintaining a temperature of 170 °C. The bath temperature was increased to 215 °C, and the adding was performed in such a way that the temperature was below or equal to 160 °C. After complete addition of the nitric acid, the solution was heated under reflux for 1 h to 165 to 170 °C. Following this, the reaction mixture was cooled in a ice bath, added to approximately 1 kg ice and diluted with 1 l water. A sodium hydroxide solution (50 percent w/v) was added dropwise until the pH value of the reaction mixture was in a neutral/weak alkaline range. This was accompanied by formation of a slightly yellow precipitate. The precipitate was separated and washed with water. The crude product of the reaction was dried over night at 110 °C, extracted with chloroform via Soxleth extraction and reduced to a dry powder in rotary evaporator. Reduction of 2-chloro-5/6-nitro-1,10-phenanthroline 2-Chloro-5/6-nitro-1,10-phenanthroline 2 (1 eq.) was dissolved in methanol and hydrogenated under stirring in the presence of the catalyst (palladium/coal 10percent, 10molpercent) in a hydrogenation plant until no further hydrogen consumption could be observed. The catalyst was filtered off and the filtrate was reduced to dryness under reduced pressure (complete conversion). Introduction of a trifluoro acetyl group to 5/6-amino-<strong>[7089-68-1]2-chloro-1,10-phenanthroline</strong> 5/6-Aminochlorophenanthroline 3 (230 mg, 1 mmol) was suspended in 20 ml water-free THF and tempered to 0 °C. Then, trifluoroacetic acid was added (275 mul, 3mmol). The initially formed precipitate dissolved after 30 min. The reaction was performed until completion under stirring for 24 hours at room temperature. The reaction mixture was reduced to a dry powder in rotary evaporator. Then, 20 ml water was added the dry substance, and the pH-value of the solution was adjusted with ammonia (25percent) to 8. The aqueous phase was extracted 3 times with 50 ml chloroform, respectively. The organic phase was dried over Na2SO4, reduced to a dry powder in a rotary evaporator. The crude product was purified with silica gel 60 (m=33 g) and chloroform/methanol (9/1; v/v) as eluent. Fractions containing pure product (examined by thin layer chromatography) were unified and reduced to a dry powder in a rotary evaporator (m=205 mg, 63percent yield). Coupling of TFA-protected 2-chloroaminophenanthroline and ethinylaniline Triphenylphosphine (30 mg, 115 mumol), [Pd(PPh3)2]Cl2 (20 mg, 285 mumol) and copper(I)iodide (16 mg, 84 mumol) were placed in a 100 ml three-necked flask and suspended in 30 ml methanol. The educt trifluoroacetyl-5/6-aminochlorophenanthroline 4 (205 mg, 466 mumol) was transferred into the flask with 20 ml methanol. The reaction mixture was tempered to 40 °C, and nitrogen was fed into. Ethinylaniline (200 mg, 1.7 mmol) was solved in a few millilitres methanol and added to the reaction mixture. Then, DIPEA (N,N-diisopropylethylamine, 2 ml) was added, and the reaction mixture was stirred over night. After this, mixture was extracted three times with 50 ml chloroform, respectively. The chloroform phase was washed with diluted sodium bicarbonate solution, diluted hydrochloric acid and again with sodium bicarbonate solution. Then, the chloroform phase was dried over Na2SO4 and purified with an aluminium oxide column and chloroform. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[2-[(4?-Aminophenylen)ethynylen]-l ,1 0-phenanthrolin-5/6-yl]amine 5 (1 eq.), DTPAdianhydride and triethylamine (5 eq.) were stirred in DMF under argon for 2 h at 80°C. The solvents were removed under reduced pressure. The residue was purified by RP-HPLC(water/MeCN).A potential problem regards the coupling of the antenna (compound 5) with the chelator (DTPA-anhydride) as the used DTPA- anhydride has two activated acid groups, but only the monosubstituted product is desired. The formation of a disubstituted product was reduced by applying the suitable excess of DTPA as described above and by a reaction design thatkeeps the concentration of compound 5 as small as possible. | ||
Example 1: Syntheis of the amino-reactive phosphorescent dye of the invention Nitration of <strong>[7089-68-1]2-chloro-1,10-phenanthroline</strong> 150 ml concentrated sulphuric acid was placed in a 500 ml three-necked flask and <strong>[7089-68-1]2-Chloro-1,10-phenanthroline</strong> 1 (CAS-Nr. 7089-68-1)(30g) was added while cooled with ice and stirred. The solution was heated in an oil bath to 180 °C. At 80 °C, the solution boiled and a strong smoke emission could be observed. At 160 °C, nitric acid (65 percent, 80 ml) was added dropwise while maintaining a temperature of 170 °C. The bath temperature was increased to 215 °C, and the adding was performed in such a way that the temperature was below or equal to 160 °C. After complete addition of the nitric acid, the solution was heated under reflux for 1 h to 165 to 170 °C. Following this, the reaction mixture was cooled in a ice bath, added to approximately 1 kg ice and diluted with 1 l water. A sodium hydroxide solution (50 percent w/v) was added dropwise until the pH value of the reaction mixture was in a neutral/weak alkaline range. This was accompanied by formation of a slightly yellow precipitate. The precipitate was separated and washed with water. The crude product of the reaction was dried over night at 110 °C, extracted with chloroform via Soxleth extraction and reduced to a dry powder in rotary evaporator. Reduction of 2-chloro-5/6-nitro-1,10-phenanthroline 2-Chloro-5/6-nitro-1,10-phenanthroline 2 (1 eq.) was dissolved in methanol and hydrogenated under stirring in the presence of the catalyst (palladium/coal 10percent, 10molpercent) in a hydrogenation plant until no further hydrogen consumption could be observed. The catalyst was filtered off and the filtrate was reduced to dryness under reduced pressure (complete conversion). Introduction of a Boc group to 5/6-amino-<strong>[7089-68-1]2-chloro-1,10-phenanthroline</strong> Alternatively, the amine group of <strong>[7089-68-1]2-chloro-1,10-phenanthroline</strong> 3 may be protected with a Boc group. To do this, 5/6-amino-<strong>[7089-68-1]2-chloro-1,10-phenanthroline</strong> (1 eq.) was dissolved in dry DMF and triethylamine (5 eq.). Then, DMAP (1.1 eq.) and di-t-butyldicarbonate (2 eq.) were added The solution was stirred at room temperature for 20 h. Then, water was added and the aqueous phase was extracted three times with diethylether. The combined organic phases were dried over Na2SO4 and concentrated to dryness. The crude product was purified with silica gel (CH2Cl2). (63percent yield). Coupling of the Boc-protected 2-chloro-5/6-amino-1,10-phenanthroline and 4-ethinylaniline Triphenylphosphine (30 molpercent), [Pd(PPh3)2]Cl2 (3molpercent), the protected 2-chloro-5/6-amino-1,10-phenanthroline 4 (1 eq.) and copper(I)iodide (2molpercent) were placed in a three-necked flask and suspended in 30 ml methanol. The 4-ethinylaniline (1.2 eq.) was added dissolved in 20 ml methanol. The reaction mixture was refluxed for 10 h. The mixture was extracted three times with dichloromethan, respectively. The combined organic phases were washed with water and brine before being concentrated to dryness. Purification by flash-chromatography yielded compound 5 as a brown solid. Coupling of the 19 Boc-protected [2-[(4'-aminophenylen)ethynylen]-1,10-phenanthrolin-5/6-yl]amine and DTPA-anhydride [2-[(4'-Aminophenylen)ethynylen]-1,10-phenanthrolin-5/6-yl]amine 5 (1 eq.), DTPA-dianhydride and triethylamine (5 eq.) were stirred in DMF under argon for 2 h at 80°C. The sovents were removed under reduced pressure. The residue was purified by RP-HPLC (water/MeCN). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Triphenylphosphine (30 molpercent), [Pd(PPh3)2]012 (3molpercent), the protected 2-chloro-5/6-amino- 1,10-phenanthroline 4 (1 eq.) and copper(l)iodide (2molpercent) were placed in a three-neckedflask and suspended in 30 ml methanol. The 4-ethinylaniline (1.2 eq.) was added dissolved in20 ml methanol. The reaction mixture was refluxed for 10 h. The mixture was extracted three times with dichloromethane, respectively. The combined organic phases were washed with water and brine before being concentrated to dryness. Purification by flash-chromatography yielded compound 5 as a brown solid.Compound 4 was converted in a Sonogashira cross coupling reaction to the antennacomponent (compound 5). For this reaction, chloride was chosen as leaving group, because the starting material of the synthesis, <strong>[7089-68-1]2-chloro-1,10-phenanthroline</strong>, is readily available at amuch lower price or easier obtainable than corresponding bromide or iodine compoundsusually used. Due to the spatial proximity of the chloride in position 2 and the nitrogen atomin position 1 of the phenanthroline ring, the palladium catalyst is coordinated in more favorable position by intramolecular interactions, whereby the Sonogashira cross coupling reaction can take place with a good yield, and the undesired Glaser reaction is restrained.This could also be achieved by keeping the concentration of the 4-ethinylalanine small as possible. Further, the isolation of the antenna compound (compound 5) is complex due to itsrigid molecular structure, its very poor solubility and the similar polarity of side products and degradation products of the catalyst, but is possible by applying a very shallow slope of the gradient from pure dichloromethane to a mixture of dichloromethane and methanol (10:5) in a flash chromatography. | ||
Example 1: Syntheis of the amino-reactive phosphorescent dye of the invention Nitration of <strong>[7089-68-1]2-chloro-1,10-phenanthroline</strong> 150 ml concentrated sulphuric acid was placed in a 500 ml three-necked flask and <strong>[7089-68-1]2-Chloro-1,10-phenanthroline</strong> 1 (CAS-Nr. 7089-68-1)(30g) was added while cooled with ice and stirred. The solution was heated in an oil bath to 180 °C. At 80 °C, the solution boiled and a strong smoke emission could be observed. At 160 °C, nitric acid (65 percent, 80 ml) was added dropwise while maintaining a temperature of 170 °C. The bath temperature was increased to 215 °C, and the adding was performed in such a way that the temperature was below or equal to 160 °C. After complete addition of the nitric acid, the solution was heated under reflux for 1 h to 165 to 170 °C. Following this, the reaction mixture was cooled in a ice bath, added to approximately 1 kg ice and diluted with 1 l water. A sodium hydroxide solution (50 percent w/v) was added dropwise until the pH value of the reaction mixture was in a neutral/weak alkaline range. This was accompanied by formation of a slightly yellow precipitate. The precipitate was separated and washed with water. The crude product of the reaction was dried over night at 110 °C, extracted with chloroform via Soxleth extraction and reduced to a dry powder in rotary evaporator. Reduction of 2-chloro-5/6-nitro-1,10-phenanthroline 2-Chloro-5/6-nitro-1,10-phenanthroline 2 (1 eq.) was dissolved in methanol and hydrogenated under stirring in the presence of the catalyst (palladium/coal 10percent, 10molpercent) in a hydrogenation plant until no further hydrogen consumption could be observed. The catalyst was filtered off and the filtrate was reduced to dryness under reduced pressure (complete conversion). Introduction of a Boc group to 5/6-amino-<strong>[7089-68-1]2-chloro-1,10-phenanthroline</strong> Alternatively, the amine group of <strong>[7089-68-1]2-chloro-1,10-phenanthroline</strong> 3 may be protected with a Boc group. To do this, 5/6-amino-<strong>[7089-68-1]2-chloro-1,10-phenanthroline</strong> (1 eq.) was dissolved in dry DMF and triethylamine (5 eq.). Then, DMAP (1.1 eq.) and di-t-butyldicarbonate (2 eq.) were added The solution was stirred at room temperature for 20 h. Then, water was added and the aqueous phase was extracted three times with diethylether. The combined organic phases were dried over Na2SO4 and concentrated to dryness. The crude product was purified with silica gel (CH2Cl2). (63percent yield). Coupling of the Boc-protected 2-chloro-5/6-amino-1,10-phenanthroline and 4-ethinylaniline Triphenylphosphine (30 molpercent), [Pd(PPh3)2]Cl2 (3molpercent), the protected 2-chloro-5/6-amino-1,10-phenanthroline 4 (1 eq.) and copper(I)iodide (2molpercent) were placed in a three-necked flask and suspended in 30 ml methanol. The 4-ethinylaniline (1.2 eq.) was added dissolved in 20 ml methanol. The reaction mixture was refluxed for 10 h. The mixture was extracted three times with dichloromethan, respectively. The combined organic phases were washed with water and brine before being concentrated to dryness. Purification by flash-chromatography yielded compound 5 as a brown solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | 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 |
---|---|---|
With copper(l) iodide; dichlorobis(tri-O-tolylphosphine)palladium; triphenylphosphine; In N,N-dimethyl-formamide; at 80 - 90℃; for 12h;Inert atmosphere; | Tris (4-iodobenzene) amine, 4-ethynylaniline, triphenylphosphine, bis (triphenylphosphine) palladium dichloride, cuprous iodide,Now steamed N, N- dimethylformamide,Now steamed triethylamine was added to a reaction vessel equipped with a thermometer and reflux condenser,The reaction was heated to 80 ° C for 12 hours under mechanical stirring and nitrogen protection, the temperature was raised to 90 ° C to distill off most of the triethylamine,After cooling to room temperature in the deionized water and washed with deionized water 3 to 4 times until the filtrate was colorless,After drying in vacuo at 80 ° C for 6 to 12 hours, dichloromethane was used as a developing solvent to give a pale yellow solid by column chromatography.(4- (2- (4-aminophenyl) ethynyl) phenyl) amine; tris (4-iodophenyl) amine, 4ethynylaniline, triphenylphosphine,Bis (triphenylphosphine) palladium dichloride, cuprous iodide, N, N-dimethylformamide,Triethylamine in a molar ratio of 1: 3.45: 0.15: 0.01: 0.040: 55: 66. (Where the maximum molar ratio of 1:3.45 to 3.50: 0.10 to 0.20: 0.01 to 0.03: 0.040 to 0.050: 53 to 56: 65 to 68).The monomer obtained in this example |