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| CAS No. : | 63927-22-0 |
| Formula : | C9H6BrN |
| M.W : | 208.06 |
| SMILES Code : | C1=NC=CC2=CC=CC(=C12)Br |
| MDL No. : | MFCD04973298 |
| InChI Key : | DPRIHFQFWWCIGY-UHFFFAOYSA-N |
| Pubchem ID : | 9859134 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302-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 |
|---|---|---|
| 59% | To a 100 mL round-bottomed flask equipped with condenser and N2 inlet were added 2.46 g (11.8 mmol) <strong>[63927-22-0]8-bromoisoquinoline</strong>, 1.68 mL (14.1 mmol) benzyl bromide, and 10 mL ethanol. The solution was heated at reflux for 6 hr, cooled, and evaporated. The oil was dissolved in 50 mL methanol, and 1.73 g (27.6 mmol) sodium cyanoborohydride was added. The solution was stirred at room temperature for 5 days, then diluted with water and extracted with three portions of ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was chromatographed on silica gel using hexane/ethyl acetate to afford 1.98 g (59percent) of an oil. 1H-NMR (delta, CDCl3): 2.68 (m, 2H), 2.88 (m, 2H), 3.68 (m, 2H), 3.75 (m, 2H), 7.0-7.1 (m, 2H), 7.2-7.4 (m, 6H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In sulfuric acid; | 8-bromoisoquinoline (24). To 7.0 mL (60.0 mmol) 2-bromobenzaldehyde (23) was added 10.0 mL (69.0 mmol) aminoacetaldehyde diethyl acetal. After 3 h at 100° C., the reaction mixture was cooled to room temperature and the layers separated. The organic layer was purified by vaccum distillation to give 15.89 g bromobenzalaminoacetal (b.p. 141-148° C. at approximately 1 mm Hg). To 143 g concentrated sulfuric acid at 0° C. was added 15.89 g bromobenzalaminoacetal. With mechanical stirring, the resulting mixture was added in portions over 5 min to 20 g phosphoric anhydride in 10 g concentrated sulfuric acid maintained at 160° C. After 25 min at 160° C., the reaction mixture was cooled, poured onto ice and washed with 300 mL ethyl ether. The aqueous layer was basified with solid NaOH to pH=10 and extracted with EtOAc repeatedly. The combined EtOAc layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (75*110 mm silica gel, linear gradient 0.5-3percent (10percent NH4H:MeOH):CH2CI2) produced 24. 1H NMR (CDCl3, 400 MHz) 89.627 (s, 1H, ArH); 8.622 (d, 1H, J=5.67 Hz, ArH); 7.858 (dd, 1H, J=0.87, 7.45 Hz, ArH); 7.799 (d, 1H, J=8.32 Hz, ArH); 7.631 (d, 1H, J=5.76 Hz, ArH); 7.538 (dd, 1H, J=7.50, 8.23 Hz, ArH); MS (Electrospray): m/z 207.9, 209.0 (M+H, 79Br, 81Br). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With copper(I) iodide; triethylamine;bis(triphenylphosphine)palladium(II) dichloride; In dichloromethane; | EXAMPLE 72 Preparation of 3-(8-isoquinolinyl)-2-propyn-1-ol In an inert atmosphere, 0.068 g of bis(triphenylphosphine)palladium dichloride and 0.013 g of cuprous iodide was added with stirring to a deoxygenated solution of 1 g of <strong>[63927-22-0]8-bromoisoquinoline</strong>, 0.56 mL of propargyl alcohol and 2 mL of triethylamine in 25 mL of dichloromethane. The mixture was stirred at room temperature for 2 hours and then at reflux for 20 hours. The cooled reaction was filtered and the filtrate was concentrated in vacuo. The residual oil was purified by HPLC (ethyl acetate-toluene; 2:3) to yield 0.4 g of 3-(8-isoquinolinyl)-2-propyn-1-ol, mp 138°-139° C. | |
| With copper(I) iodide; triethylamine;bis(triphenylphosphine)palladium(II) dichloride; In dichloromethane; | EXAMPLE 72 Preparation of 3-(8-isoquinolinyl)-2-propyn-1-ol In an inert atmosphere, 0.068 g of bis(triphenylphosphine)palladium dichloride and 0.13 g of cuprous iodide was added with stirring to a deoxygenated solution of 1 g of <strong>[63927-22-0]8-bromoisoquinoline</strong>, 0.56 mL of propargyl alcohol and 2 mL of triethylamine in 25 mL of dichloromethane. The mixture was stirred at room temperature for 2 hours and then at reflux for 20 hours. The cooled reaction was filtered and the filtrate was concentrated in vacuo. The residual oil was purified by HPLC (ethyl acetate-toluene; 2:3) to yield 0.4 g of 3-(8-isoquinolinyl)-2-propyne-1-ol, mp 138°-139° C. | |
| With copper(I) iodide; triethylamine;bis(triphenylphosphine)palladium(II) dichloride; In dichloromethane; | EXAMPLE 72 Preparation of 3-(8-isoquinolinyl)-2-propyn-1-ol In an inert atmosphere, 0.068 g of bis(triphenylphosphine)palladium dichloride and 0.013 g of cuprous iodide was added with stirring to a deoxygenated solution of 1 g of <strong>[63927-22-0]8-bromoisoquinoline</strong>, 0.56 mL of propargyl alcohol and 2 mL of triethylamine in 25 mL of dichloromethane. The mixture was stirred at room temperature for 2 hours and then at reflux for 20 hours. The cooled reaction was filtered and the filtrate was concentrated in vacuo. The residual oil was purified by HPLC (ethyl acetate-toluene; 2:3) to yield 0.4 g of 3-(8-isoquinolinyl)-2-propyne-1-ol, mp 138°-139° C. |
| With copper(I) iodide; triethylamine;bis(triphenylphosphine)palladium(II) dichloride; In dichloromethane; | EXAMPLE 168 Preparation of 3-(8-isoquinolinyl)-2-propyn-1-ol In an inert atmosphere. 0.068 g of bis(triphenylphosphine)palladium dichloride and 0.013 g of cuprous iodide was added with stirring to a deoxygenated solution of 1 g of <strong>[63927-22-0]8-bromoisoquinoline</strong>, 0.56 mL of propargyl alcohol and 2 mL of triethylamine in 25 mL of dichloromethane. The mixture was stirred at room temperature for 2 hours and then at reflux for 20 hours. The cooled reaction was filtered and the filtrate was concentrated in vacuo. The residual oil was purified by HPLC (ethyl acetate-toluene; 2:3) to yield 0.4 g of -(8-isoquinolinyl)-2-propyne-1-ol, mp 138°-139° C. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Inert atmosphere; | 1-(8-naphthyl)-isoquinoline (8-NAIQ). 1-(8-naphthyl)-isoquinoline was obtained from thereaction of <strong>[63927-22-0]8-bromoisoquinoline</strong> and naphthalene-1-boronic acid by Suzuki coupling [8]. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 78% | monophosphine 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphino)ferrocene; bis(dibenzylideneacetone)-palladium(0); In tetrahydrofuran; at 80℃;Inert atmosphere; | To a suspension of <strong>[63927-22-0]8-bromoisoquinoline</strong> (2.Og, 9.7mmol), Q-phos (68mg, 0.096mmol) and Pd(dba)2 (132mg, 0.14mmol) in dry THF (3OmL) was added 4OmL of (2-tert- butoxy-2-oxoethyl)zinc(II) bromide solution under N2 protection. The resulting mixture was heated at 80 0C overnight. The solvent was evaporated under vacuum and the crude residue was diluted with ethyl acetate (10OmL) and washed with water (3 x 5OmL). The combined organic layer was washed with brine, dried over Na2SO4 and the solvent was evaporated under vacuum to give a residue which was purified with silica gel chromatography to give tert-butyl 2- (isoquinolin-8-yl)acetate (1.85g, 78percent). |
| 75% | With monophosphine 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphino)ferrocene; bis(dibenzylideneacetone)-palladium(0); In tetrahydrofuran; at 80℃;Inert atmosphere; | Preparation of Compound 31-12[004881 To a suspension of <strong>[63927-22-0]8-bromoisoquinoline</strong> (1.5 g, 7.3mmol), Q-phos (52 mg, 0.O73mmol) and Pd(dba)2 (63 mg,0.1 lmmol) in dry THF (30 mL) was added 40 mL of (2-tert-butoxy-2-oxoethyl)zinc(II) bromide solution (20 ml, 0.5 M) under N2. The resulting mixture was heated at 80°C overnight. The solvent was evaporated under vacuum and the crude residue was diluted with ethyl acetate and washed with water. The combined organic layer was washed with brine, dried over Na2SO4 and the solvent was evaporated under vacuum to give a residue which was purified by silica gel chromatography to give tert-butyl 2-(isoquinolin-8-yl)acetate (Compound 31-12, 1.33g, yield 75percent) as a white solid. MS m/z 244[M+1]. ?H NMR (400 MHz, CDC13) 59.46 (s, 1H), 8.56-8.54(d, J= 5.6 Hz 1H), 7.76-7.74 (d, J= 8.0 Hz 1H), 7.66-7.6 1 (m, 2H),7.48-7.47(d, J= 6.8 Hz 1H ),4.07(s,2H), 1.42(s,9H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With sulfuric acid; at 130 - 140℃; for 0.5h; | The oil was dropped into 5OmL of concentrated H2SO4 and the mixture was heated to 130-140 0C for 30mins, then the reaction mixture was poured into 50OmL if ice-water and adjust to pH~8 with 5N sodium hydroxide solution. The aqueous solution was extracted with DCM (250mLX5) and washed with water (3 x 5OmL). The combined organic layer was washed with brine, dried over Na2SO4 and the solvent was evaporated under vacuum. The crude solid was purified with silica gel to give 8- bromoisoquinoline (2.2g, two steps 10.6%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With potassium phosphate; copper(l) iodide; L-proline; In N,N-dimethyl-formamide; at 150℃; for 16h; | Example No. 58; Preparation of Compound No. 58 [0355] A solution of 2,8-dimethyl-2,3 ,4,5-tetrahydro- lH-pyrido[4,3-b]indole (0.1 g, 0.499 mmol), <strong>[63927-22-0]8-bromoisoquinoline</strong> (0.155 g, 0.748 mmol), potassium phosphate (0.317 g, 1.495 mmol), Cul (9 mg, 0.047 mmol) and L-Proline (11 mg, 0.095 mmol) in dry DMF (3 mL) was heated at 150 °C for 16h. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain crude, which was purified by reverse phase HPLC to yield 5- (isoquinolin-8-yl)-2,8-dimethyl-2,3,4,5-tetrahydro-lH-pyrido[4,3-b]indole. 1H NMR (TFA salt, CD3OD) d (ppm): 8.8 (d, 1H), 8.62 (d, 1H), 8.42 (bs, 1H), 8.4 (d, 1H), 8.3 (t, 1H), 8.0 (d, 1H), 7.42 (s, 1H), 7.0 (d, 1H), 6.87 (bs, 1H), 4.7 (d, 1H), 4.3 (d, 1H), 3.8 (m, 1H), 3.6 (m, 1H), 3.16 (m, 4H), 2.8 (m, 1H), 2.4 (s, 3H). | |
| With potassium phosphate; copper(l) iodide; L-proline; In N,N-dimethyl-formamide; at 150℃; for 16h; | Example No. 58: Preparation of Compound No. 58[0346] A solution of 2,8-dimethyl-2,3,4,5-tetrahydro- lH-pyrido[4,3-b]indole (0.1 g, 0.499 mmol), <strong>[63927-22-0]8-bromoisoquinoline</strong> (0.155 g, 0.748 mmol), potassium phosphate (0.317 g, 1.495 mmol), Cul (9 mg, 0.047 mmol) and L-Proline (11 mg, 0.095 mmol) in dry DMF (3 mL) was heated at 150 °C for 16h. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain crude, which was purified by reverse phase HPLC to yield 5- (isoquinolin-8-yl)-2,8-dimethyl-2,3,4,5-tetrahydro-lH-pyrido[4,3-b]indole. 1H NMR (TFA salt, D o ( pm . , H , . , H , . s, H , . , H , eta nu alpha, ), 7.42 (s, 1H), 7.0 (d, 1H), 6.87 (bs, 1H), 4.7 (d, 1H), 4.3 (d, 1H), 3.8 (m, 1H), 3.6 (m, 1H), 3.16 (m, 4H), 2.8 (m, 1H), 2.4 (s, 3H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 312 mg | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; ethanol; water; at 100℃; for 18h;Inert atmosphere; | General procedure: In an argon gas atmosphere, tetrakis(triphenylphosphine)palladium (83 mg) and a 2 M aqueous sodium carbonate solution (2.2 mL) were added to a mixture of <strong>[63927-22-0]8-bromoisoquinoline</strong> (300 mg), 2,4-difluorophenylboronic acid (342 mg), 1,2-dimethoxyethane (10 mL), and ethanol (1 mL), followed by stirring for 18 hours at an oil temperature of 100° C. The reaction liquid was cooled to room temperature, and then water and ethyl acetate were added thereto to perform liquid separation. The organic layer was washed with saturated brine and then dried, followed by concentration under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate), thereby obtaining 8-(2,4-difluorophenyl)isoquinoline (312 mg). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 70% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 50 - 110℃; | To a round bottomed flask containing <strong>[63927-22-0]8-bromoisoquinoline</strong> (3g, 14.4 mmol) are addedC52CO3 (13.2 g, 40.4 mmol), glycine ethyl ester hydrochloride (2.21g, 15.9 mmol), BINAP(449 mg, 0.72 mmol) and Pd2(dba)3 (0.397 g, 0.433 mmol) followed by 50 mL toluene. Theresulting brown suspension is allowed to stir at 80C for 2 h, at 50C overnight then at 110Cfor 9 h.After cooling the suspension is filtered over Celite. The celite cake is rinsed three times withEtOAc. The combined organic phase is washed with brine, dried over Na2SO4 and filtered.Evaporation of the solvents in vacuo yields 4.64 g of a brown oil. Flash-chromatography onsilica-gel (Eluent: gradient of heptane I EtOAc 90:10 to 0:100) yields 2.33 g (70%) of the subtitle compound as yellow solid.LC-B: tR = 0.47 mm; [M+H] = 231.2; 1H-NMR (CDCI3) oe: 9.41 (5, 1 H), 8.52 (d, J = 5.7 Hz, 1H), 7.58 (d, J = 5.7 Hz, 1 H), 7.53 (t, J = 7.9 Hz, 1 H), 7.20 (d, J = 8.2 Hz, 1 H), 6.54 (d, J =7.7 Hz, 1 H), 5.49 (5, 1 H), 4.34 (q, J = 7.1 Hz, 2 H), 4.09 (d, J = 4.9 Hz, 2 H), 1.36 (t, J = 7.1Hz, 3H) |
[ 63927-22-0 ]
[ 63927-22-0 ]