Structure of 95333-17-8
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CAS No. : | 95333-17-8 |
Formula : | C9H5NO |
M.W : | 143.14 |
SMILES Code : | N#CC1=C2C=COC2=CC=C1 |
MDL No. : | MFCD10699413 |
InChI Key : | VCQONKRSTAUGEP-UHFFFAOYSA-N |
Pubchem ID : | 13307980 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
* 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 |
---|---|---|
16.2% | With sodium tetrahydroborate; nickel dichloride; In methanol; at 20℃; for 2h; | Add <strong>[95333-17-8]benzofuran-4-carbonitrile</strong> C1-1e (300 mg, 2.09 mmol) in methanol (50 mL). Nickel chloride (543 mg, 4.19 mmol) was slowly added with sodium borohydride (159 mg, 4.19 mmol) and allowed to react at room temperature for 2 hours. The mixture was filtered through celite, washed with methanol and evaporated. The crude product was purified on silica gel (dichloromethane: methanol = 10: 1), to give benzofuran-4-ylmethylamine C2-1 (50mg, 16.2% yield) as a yellow solid. |
16.2% | With sodium tetrahydroborate; nickel dichloride; In methanol; at 20℃; for 2h; | In a single-necked flask, add <strong>[95333-17-8]benzofuran-4-carbonitrile</strong> C1-1e (300 mg, 2.09 mmol), methanol (50 mL), nickel chloride (543 mg, 4.19 mmol), and slowly add sodium borohydride (159 mg, 4.19 mmol). , 2 hours reaction at room temperature.The mixture was filtered through celite, washed with methanol,The filtrate was concentrated under reduced pressure to obtain a crude product. The crude was purified on silica gel (dichloromethane:Methanol = 10: 1) to give benzofuran-4-ylmethylamine C2-1 (50 mg, 16.2% yield) as a yellow solid. |
16.2% | With sodium tetrahydroborate; nickel dichloride; In methanol; at 10 - 30℃; for 2h; | Add <strong>[95333-17-8]benzofuran-4-carbonitrile</strong> C1-1e (300 mg, 2.09 mmol) to a single-necked flaskMethanol (50 mL), nickel chloride (543 mg, 4.19 mmol), sodium borohydride (159 mg, 4.19 mmol) was slowly added, and the mixture was reacted at room temperature for 2 hours. The mixture was filtered through diatomaceous earth,It was washed with methanol, and the filtrate was concentrated under reduced pressure to obtain a crude product. The crude product was purified on silica gel(Dichloromethane: methanol = 10: 1) to obtain benzofuran-4-ylmethylamine C2-1(50 mg, 16.2% yield) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | A mixture of C1-1c and C1-1d (5 g, 25.1 mmol), zinc cyanide (4.2 g, 37.7 mmol) was sequentially added to a 100 mL three-necked flask. Tetrakistriphenylphosphine palladium (2.9 g, 2.5 mmol) and anhydrous N,N-dimethylformamide (50 mL). The reaction mixture was heated and stirred at 100 C for 18 hours under nitrogen. After cooling to room temperature, 200 mL of water was added and extracted with ethyl acetate.(200mL x 3). The combined organic phases were washed twice with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified on silica gel (petroleum ether: ethyl acetate = 100: 1), to give benzofuran-4-carbonitrile C1-1e (1.1g, 30% yield) as a pale yellow solid. The conversion product of C1-1d was separated and removed in this step. | |
30% | In a 500 mL single-necked flask, bromo-3- (2,2-diethoxyethoxy) benzene C1-1b (21 g, 72.6 mmol), 150 mL of toluene, and polyphosphoric acid (10.68 g, 108.93 mmol) were sequentially added. The reaction solution was heated at 95 C and stirred for 4 hours. After cooling to room temperature, the reaction solution was quenched with 1 L of ice water, and extracted with ethyl acetate (500 mL × 3). The combined organic phases were washed twice with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give a total of 5 g of a crude mixture of C1-1c and C1-1d. Step 3: Intermediate benzofuran-4-carbonitrile (C1-1e)In a 100 mL three-necked flask were added a mixture of C1-1c and C1-1d (5 g, 25.1 mmol), zinc cyanide (4.2 g, 37.7 mmol),Tetratriphenylphosphine palladium (2.9g, 2.5mmol)And anhydrous N, N-dimethylformamide (50 mL). The reaction mixture was heated and stirred at 100 C for 18 hours under nitrogen. After cooling to room temperature, 200 mL of water was added and extracted with ethyl acetate (200 mL X 3).The combined organic phases were washed twice with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified on silica gel (petroleum ether: ethyl acetate = 100: 1) to give benzofuran-4-carbonitrile C1-1e (1.1 g, 30% yield),As a pale yellow solid. The conversion product of C1-1d is separated and removed in this step. | |
1.1 g | In a 500 mL single-necked flask, bromo-3- (2,2-diethoxyethoxy) benzene C1-1b (21 g, 72.6 mmol), 150 mL of toluene, and polyphosphoric acid (10.68 g, 108.93 mmol) were sequentially added. The reaction solution was heated at 95 C and stirred for 4 hours.After cooling to room temperature, the reaction solution was quenched with 1 L of ice water, and extracted with ethyl acetate (500 mL × 3). The combined organic phases were washed twice with brine, dried over anhydrous sodium sulfate, filtered,Concentration under reduced pressure gave a crude mixture of C1-1c and C1-1d of 5 g.In a 100 mL three-necked flask were added a mixture of C1-1c and C1-1d (5 g, 25.1 mmol), zinc cyanide (4.2 g, 37.7 mmol),Tetratriphenylphosphine palladium (2.9 g, 2.5 mmol) and anhydrous N, N-dimethylformamide (50 mL).The reaction mixture was heated and stirred at 100 C for 18 hours under nitrogen.After cooling to room temperature, 200 mL of water was added and extracted with ethyl acetate (200 mL X 3).The combined organic phases were washed twice with brine, dried over anhydrous sodium sulfate, filtered,Concentrated under reduced pressure. The residue was purified on silica gel (petroleum ether: ethyl acetate = 100: 1),Benzofuran-4-carbonitrile C1-1e (1.1 g, 30% yield) was obtained as a pale yellow solid.The conversion product of C1-1d is separated and removed in this step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With palladium 10% on activated carbon; hydrogen; In methanol; water; at 60℃; for 18h; | Add <strong>[95333-17-8]benzofuran-4-carbonitrile</strong> C1-1e (1.1 g, 7.68 mmol), BOC anhydride (2.5 g, 11.52 mmol), methanol (50 mL) and 10% palladium on carbon (2 g, containing 50) in a 100 mL vial. %water). The reaction mixture was purged with hydrogen for 5 minutes, ventilated three times with a hydrogen balloon, and stirred at 60 C for 18 hours under a hydrogen balloon. The mixture was filtered through Celite, washed with methanol (50mL x 2)Washing the filtrate was concentrated under reduced pressure, to give compound C1-1f (1.5g, 79% yield). |
79% | With palladium 10% on activated carbon; hydrogen; at 60℃; for 18h; | In a 100 mL single-necked flask, <strong>[95333-17-8]benzofuran-4-carbonitrile</strong> C1-1e (1.1 g, 7.68 mmol), BOC anhydride (2.5 g, 11.52 mmol), methanol (50 mL), and 10% palladium carbon (2 g, containing 50 %water). The reaction mixture was purged with hydrogen for 5 minutes, vented three times with a hydrogen balloon, and stirred at 60 C. for 18 hours under a hydrogen balloon. The mixture was filtered through celite, washed with methanol (50 mL X 2), and the filtrate was concentrated under reduced pressure.Compound C1-1f (1.5 g, 79% yield) was obtained. |
79% | With palladium 10% on activated carbon; hydrogen; In methanol; at 60℃; for 18h; | Add <strong>[95333-17-8]benzofuran-4-carbonitrile</strong> C1-1e to a 100mL single-necked bottle in sequence(1.1 g, 7.68 mmol), BOC anhydride (2.5 g, 11.52 mmol),Methanol (50 mL) and 10% palladium on carbon (2 g, containing 50% water). The reaction mixture was purged with hydrogen for 5 minutes, vented three times with a hydrogen balloon, and stirred at 60 C. for 18 hours under a hydrogen balloon.The mixture was filtered through celite, washed with methanol (50 mL X 2), and the filtrate was concentrated under reduced pressure.Compound C1-1f (1.5 g, 79% yield) was obtained. |
140 mg | With palladium 10% on activated carbon; hydrogen; In methanol; at 30℃; under 2585.81 Torr; for 24h; | To a solution of <strong>[95333-17-8]benzofuran-4-carbonitrile</strong> (750 mg, 4.72 mmol, 1.00 equiv) in methyl alcohol (10.0 mL) was added Boc20 (3.09 g, l4.2mmol, 3.00 equiv) and Pd/C (4.72 mmol, 10.0 w. %, 1.00 equiv). The mixture was stirred at 30 C for 24 h under hydrogen (50.0 psi). The reaction mixture was filtered and concentrated under reduced pressure to give the crude material, which was purified by column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 50 / 1) to afford /er/-butyl N-( 2, 3-dihydrobenzofuran-4-ylmethyl) carbamate (140 mg, 562 pmol, 11.9% yield) as a colorless oil. 1H NMR (400MHz, CDCI3) d = 7.10 (t, J=8.0 Hz, 1H), 6.74 (dd, J=8.0, 14.0 Hz, 2H), 4.75 (br s, 1H), 4.59 (t, J=8.8 Hz, 2H), 4.28 (br d, J=5.6 Hz, 2H), 3.20 (t, J=8.8 Hz, 2H), 1.47 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl acetamide; at 140℃; for 12h;Inert atmosphere; | To a solution of 4-bromobenzofuran (5.20 g, 13.2 mmol, 1.00 equiv) in DMAC (50.0 mL) was added zinc cyanide (6.85 g, 58.3 mmol, 4.42 equiv) and Pd(PPh3)4 (1.52 g, 1.32 mmol, 0.100 equiv). The mixture was stirred at 140 C for 12 h under a nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate (80.0 mL), washed with brine (50.0 mL x 3), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a residue. The crude material was purified by column chromatography (petroleum ether / ethyl acetate = 50 / 1 to 0 / 1) to afford benzofuran-4-carbonitrile (1.60 g, 10.1 mmol, 76.2% yield, 90.0% purity) as a light-yellow oil. 1H NMR (400MHz, CDC13) d = 7.80 (d, J=2.0 Hz, 1H), 7.75 (d, =8.4 Hz, 1H), 7.60 (d, J=8.0 Hz, 1H), 7.38 (t, J=8.4 Hz, 1H), 7.03 - 7.00 (m, 1H). |