Structure of 1093254-29-5
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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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CAS No. : | 1093254-29-5 |
Formula : | C14H9Cl2FN2O |
M.W : | 311.14 |
SMILES Code : | N#CC1=CC(Cl)=CC(OC2=C(Cl)C=CC(CN)=C2F)=C1 |
MDL No. : | MFCD26127383 |
* 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 |
---|---|---|
1% | In a 24-well Bohdan block, ethyl 5-hydroxy-1 H-indole-2-carboxylate (0.100 g, 0.487 mmol), 2-(4-morpholinyl)ethanol (0.160 g, 1.22 mmol) and PS-triphenylphosphine (406 mg, 1.22 mmol) were dissolved in THF (1 ml_). Di-terf-butyl azodicarboxylate (1.22 M in THF, 1 ml.) was added and the block shaken overnight. The reactor block was drained into a second Bohdan block and rinsed with THF. 1 N LiOH (1 mL) was added and the reactor block shaken for 6 hours at RT. 1 N HCI (1 mL) was added and the block was drained into a 24-well plate, rinsed with THF and the solvent evaporated. The residue was dissolved in DMF and filtered to remove salts. To the DMF solution was added 3-[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5- chlorobenzonitrile (50 mg, 0.161 mmol) followed by HATU (61.1 mg, 0.161 mmol) and DIPEA (30 muL, 0.222 mmol) and the reaction mixture stirred overnight. The resulting solution was diluted to 2 mL with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1 % TFA) to afford the title compound (0.003 g, 1%) as a glass. 1H NMR (400 MHz, CDCI3;/ delta ppm 9.05 - 9.11 (m, 1 H), 7.35 - 7.37 (m, 1 H), 7.34 (s, 1 H), 7.27 - 7.31 (m, 2 H), 7.15 - 7.18 (m, 1 H), 7.05 (d, 1 H), 7.02 (dd, 1 H), 6.99 (dd, 1 H), 6.79 (d, 1 H), 6.50 - 6.57 (m, 1 H), 4.73 (d, 2 H), 4.13 - 4.18 (m, 2 H), 3.72 - 3.79 (m, 4 H), 2.82 - 2.90 (m, 2 H), 2.60 - 2.69 (m, 4 H). LCMS m/z 583.1 (M+1 ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2% | In a 24-well Bohdan block, ethyl 5-hydroxy-1 /-/-indole-2-carboxylate (0.100 g, 0.487 mmol), 2-(1-methyl-2-pyrrolidinyl)ethanol (0.157 g, 1.22 mmol) and PS- triphenylphosphine (406 mg, 1.22 mmol) were dissolved in THF (1 ml_). Di-terf-butyl azodicarboxylate (1.22 M in THF, 1 ml.) was added and the block shaken overnight. The reactor block was drained into a second Bohdan block and rinsed with THF. 1 N LiOH (1 ml.) was added and the reactor block shaken for 6 hours at RT. 1 N HCI (1 ml.) was added and the block was drained into a 24-well plate, rinsed with THF and the solvent evaporated. The residue was dissolved in DMF and filtered to remove salts. To the DMF solution was added 3-[3-(aminomethyl)-6-chloro-2- fluorophenyl]oxy}-5-chlorobenzonitrile (50 mg, 0.161 mmol) followed by HATU (61.1 mg, 0.161 mmol) and DIPEA (30 mul_, 0.222 mmol) and the reaction mixture stirred overnight. The resulting solution was diluted to 2 ml. with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA) to afford the title compound (0.007 g, 2%) as a glass. 1H NMR (400 MHz, CDCI3)/ delta ppm 9.50 (br. s., 1 H), 7.22 - 7.39 (m, 4 H), 7.13 - 7.18 (m, 1 H), 7.05 - 7.12 (m, 1 H), 6.95 - 7.03 (m, 2 H), 6.84 - 6.91 (m, 2 H), 4.66 - 4.75 (m, 2 H), 4.07 - 4.17 (m, 1 H), 3.91 - 4.00 (m, 1 H), 3.27 - 3.41 (m, 1 H), 2.76 - 2.91 (m, 4 H), 2.39 - 2.51 (m, 1 H), 2.24 - 2.36 (m, 1 H), 2.16 (br. s., 2 H), 1.91 - 2.08 (m, 3 H). LCMS m/z 581.1 (M+1 ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6% | In a 24-well Bohdan block, ethyl 5-hydroxy-1 /-/-indole-2-carboxylate (0.100 g, 0.487 mmol), 1 ,3-butanediol (0.1 10 g, 1.22 mmol) and PS-triphenylphosphine (406 mg, 1.22 mmol) were dissolved in THF (1 mL). Di-terf-butyl azodicarboxylate (1.22 M in THF, 1 mL) was added and the block shaken overnight. The reactor block was drained into a second Bohdan block and rinsed with THF. 1 N LiOH (1 mL) was added and the reactor block shaken for 6 hours at RT. 1 N HCI (1 mL) was added and the block was drained into a 24-well plate, rinsed with THF and the solvent evaporated. The residue was dissolved in DMF and filtered to remove salts. To the DMF solution was added 3-[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5- chlorobenzonitrile (50 mg, 0.161 mmol) followed by HATU (61.1 mg, 0.161 mmol) and DIPEA (30 muL, 0.222 mmol) and the reaction mixture stirred overnight. The resulting solution was diluted to 2 mL with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1 % TFA) to afford the title compound (0.016 g, 6%) as a glass. 1H NMR (400 MHz, CDCI3): delta ppm 9.42 (br. s., 1 H), 7.26 - 7.38 (m, 4 H), 7.16 (t, 1 H), 7.05 (d, 1 H), 7.00 - 7.03 (m, 1 H), 6.92 - 6.98 (m, 1 H), 6.80 (d, 1 H), 6.69 (t, 1 H), 4.72 (d, 2 H), 4.07 - 4.24 (m, 3 H), 1.89 - 2.02 (m, 2 H), 1.29 (d, 3 H). LCMS m/z 540.3 (M-1 ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3% | In a 24-well Bohdan block, ethyl 5-hydroxy-1 /-/-indole-2-carboxylate (0.100 g, 0.487 mmol), 3-(dimethylamino)-1-propanol (0.126 g, 1.22 mmol) and PS- triphenylphosphine (406 mg, 1.22 mmol) were dissolved in THF (1 mL). Di-terf-butyl azodicarboxylate (1.22 M in THF, 1 mL) was added and the block shaken overnight. The reactor block was drained into a second Bohdan block and rinsed with THF. 1 N LiOH (1 mL) was added and the reactor block shaken for 6 hours at RT. 1 N HCI (1 mL) was added and the block was drained into a 24-well plate, rinsed with THF and the solvent evaporated. The residue was dissolved in DMF and filtered to remove salts. To the DMF solution was added 3-[3-(aminomethyl)-6-chloro-2- fluorophenyl]oxy}-5-chlorobenzonitrile (50 mg, 0.161 mmol) followed by HATU (61.1 mg, 0.161 mmol) and DIPEA (30 muL, 0.222 mmol) and the reaction mixture stirred overnight. The resulting solution was diluted to 2 mL with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1 % TFA) to afford the title compound (0.008 g, 3%) as a glass. 1H NMR (400 MHz, CDC3-d): delta ppm <n="116"/>9.26 (br. s., 1 H), 7.30 - 7.36 (m, 2 H), 7.25 - 7.27 (m, 1 H), 7.22 - 7.24 (m, 1 H), 7.13 (t, 1 H), 6.95 - 7.00 (m, 2 H), 6.88 (dd, 1 H), 6.79 (d, 1 H), 6.73 - 6.78 (m, 1 H), 4.69 (d, 2 H), 4.01 (t, 2 H), 3.68 - 3.75 (m, 2 H), 3.00 - 3.08 (m, 2 H), 2.68 (s, 6 H). LCMS m/z 555.2 (M+1 ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3% | In a 24-well Bohdan block, ethyl 5-hydroxy-1 H-indole-2-carboxylate (0.100 g, 0.487 mmol), 2-(dimethylamino)ethanol (0.109 g, 1.22 mmol) and PS-triphenylphosphine (406 mg, 1.22 mmol) were dissolved in THF (1 mL). Di-terf-butyl azodicarboxylate (1.22 M in THF, 1 mL) was added and the block shaken overnight. The reactor block was drained into a second Bohdan block and rinsed with THF. 1 N LiOH (1 mL) was added and the reactor block shaken for 6 hours at RT. 1 N HCI (1 mL) was added <n="118"/>and the block was drained into a 24-well plate, rinsed with THF and the solvent evaporated. The residue was dissolved in DMF and filtered to remove salts. To the DMF solution was added 3-[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5- chlorobenzonitrile (50 mg, 0.161 mmol) followed by HATU (61.1 mg, 0.161 mmol) and DIPEA (30 mul_, 0.222 mmol) and the reaction mixture stirred overnight. The resulting solution was diluted to 2 ml. with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1 % TFA) to afford the title compound (0.008 g, 3%) as a glass. 1H NMR (400 MHz, CDCI3): delta ppm 9.28 (s, 1 H), 7.31 - 7.38 (m, 3 H), 7.29 (d, 1 H), 7.14 - 7.17 (m, 1 H), 7.00 - 7.04 (m, 2 H), 6.96 (dd, 1 H), 6.80 - 6.83 (m, 1 H), 6.73 (t, 1 H), 4.72 (d, 2 H), 4.19 (t, 2 H), 3.04 (t, 2 H), 2.59 (s, 6 H). LCMS m/z 541.1 (M+1 ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | In a 1 dram vial, 3-[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5- chlorobenzonitrile (25 mg, 0.080 mmol), DIPEA (0.014 mL, 0.080 mmol) and 2-(3- pyridinyl)-1 ,3-thiazole-4-carboxylic acid (16.57 mg, 0.080 mmol) were dissolved in DMF (1 mL). HATU was added (30.6 mg, 0.080 mmol) and the solution stirred overnight. The reaction mixture was diluted to 2 mL with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA) to afford the title compound (0.021 g, 42%) as a white solid. 1H NMR (400 MHz, CDCI3;.' δ ppm 9.40 (br. s., 1 H), 8.75 - 8.86 (m, 1 H), 8.58 (d, 1 H), 8.34 (s, 1 H), 7.89 (t, 1 H), 7.81 (dd, 1 H), 7.35 - 7.41 (m, 1 H), 7.33 (t, 1 H), 7.26 - 7.31 (m, 1 H), 7.16 (t, 1 H), 6.99 (s, 1 H), 4.75 (d, 2 H). LCMS m/z 498.9 (M+1 ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | In a 1 dram vial, 3-[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5- chlorobenzonitrile (25 mg, 0.080 mmol), DIPEA (0.014 mL, 0.080 mmol) and 1 H- <strong>[37718-11-9]pyrazole-4-carboxylic acid</strong> (9.01 mg, 0.080 mmol) were dissolved in DMF (1 mL). HATU was added (30.6 mg, 0.080 mmol) and the solution stirred overnight. The reaction mixture was diluted to 2 mL with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1 percent TFA) to afford the title compound (0.013 g, 31 percent) as a white solid. 1H NMR (400 MHz, Acetone-cfe): delta ppm 8.09 (br. s., 2 H), 8.00 (br. s., 1 H), 7.63 (t, 1 H), 7.40 - 7.48 (m, 2 H), 7.36 - 7.40 (m, 2 H), 5.63 (br. s., 1 H), 4.60 (d, 2 H). LCMS m/z 404.9 (M+1 ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; | In a 1 dram vial, 3-[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5- chlorobenzonitrile (25 mg, 0.080 mmol), DIPEA (0.014 mL, 0.080 mmol) and 1 ,2,3- thiadiazole-4-carboxylic acid (10.46 mg, 0.080 mmol) were dissolved in DMF (1 mL). HATU was added (30.6 mg, 0.080 mmol) and the solution stirred overnight. The reaction mixture was diluted to 2 mL with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1 % TFA) to afford the title compound (0.016 g, 46%) as a white solid. 1H NMR (400 MHz, Acetone-d6): delta ppm 9.55 (s, 1 <n="110"/>H), 8.94 (br. s., 1 H), 7.63 (t, 1 H), 7.53 (t, 1 H), 7.41 - 7.46 (m, 1 H), 7.37 - 7.41 (m, 2 H), 4.79 (d, 2 H). LCMS m/z 422.8 (M+1 ). |