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CAS No. : | 1354777-44-8 | MDL No. : | MFCD20501470 |
Formula : | C7H4BrN3O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | N/A |
M.W : | 242.03 g/mol | Pubchem ID : | - |
Synonyms : |
|
Num. heavy atoms : | 13 |
Num. arom. heavy atoms : | 9 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 48.55 |
TPSA : | 78.87 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.85 cm/s |
Log Po/w (iLOGP) : | 0.91 |
Log Po/w (XLOGP3) : | 1.31 |
Log Po/w (WLOGP) : | 1.42 |
Log Po/w (MLOGP) : | 1.4 |
Log Po/w (SILICOS-IT) : | 1.57 |
Consensus Log Po/w : | 1.32 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.56 |
Log S (ESOL) : | -2.61 |
Solubility : | 0.591 mg/ml ; 0.00244 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.57 |
Solubility : | 0.656 mg/ml ; 0.00271 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.77 |
Solubility : | 0.41 mg/ml ; 0.00169 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.83 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
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* 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 |
---|---|---|
Multi-step reaction with 2 steps 1.1: glacial acetic acid / 0.17 h / 25 °C 1.2: 0.5 h 2.1: lithium hydroxyde monohydrate; lithium hydroxide monohydrate / tetrahydrofuran; methanol / 1 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With lithium hydroxyde monohydrate; lithium hydroxide monohydrate In tetrahydrofuran; methanol at 25℃; for 1h; | 16.2 Step 2: To a solution of methyl 6-bromo-3H-benzotriazole-4-carboxylate (440 mg, 1.72 mmol) in THF (4 mL), MeOH (2 mL), and H2O (2 mL) was added LiOH•H2O (216.33 mg, 5.16 mmol). The reaction was stirred at 25 °C for 1 hour. The reaction was diluted with water, washed with ethyl acetate, acidified to pH = 2 using HCl (2M), filtered, and the solid was dried under reduced pressure to give 6-bromo-3H-benzotriazole-4- carboxylic acid (450 mg, crude). LCMS (ESI): m/z: [M + H] calculated for C7H5BrN3O2: 241.95; found 241.8;1H NMR (400 MHz, DMSO-d6) δ ppm 16.10 (br s, 1H), 8.64 (s, 1H), 8.10 (s, 1H). | |
With lithium hydroxyde monohydrate; lithium hydroxide monohydrate In tetrahydrofuran; methanol at 25℃; for 1h; | 16.2 Step 2: To a solution of methyl 6-bromo-3H-benzotriazole-4-carboxylate (440 mg, 1.72 mmol) in THF (4 mL), MeOH (2 mL), and H2O (2 mL) was added LiOH•H2O (216.33 mg, 5.16 mmol). The reaction was stirred at 25 °C for 1 hour. The reaction was diluted with water, washed with ethyl acetate, acidified to pH = 2 using HCl (2M), filtered, and the solid was dried under reduced pressure to give 6-bromo-3H-benzotriazole-4- carboxylic acid (450 mg, crude). LCMS (ESI): m/z: [M + H] calculated for C7H5BrN3O2: 241.95; found 241.8;1H NMR (400 MHz, DMSO-d6) δ ppm 16.10 (br s, 1H), 8.64 (s, 1H), 8.10 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1-propanephosphonic acid cyclic anhydride; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 1 h / 25 °C 2: anhydrous sodium carbonate; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 1 h / 100 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 1-propanephosphonic acid cyclic anhydride; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 1 h / 25 °C 2: anhydrous sodium carbonate; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 1 h / 100 °C / Inert atmosphere 3: hydrogenchloride / lithium hydroxide monohydrate; ethyl acetate / 0.5 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
550 mg | With 1-propanephosphonic acid cyclic anhydride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 25℃; for 1h; | 16.3 Step 3: To a solution of 6-bromo-3H-benzotriazole-4-carboxylic acid (430 mg, 1.78 mmol) and (1R)-1-[3-(difluoromethyl)-2-fluoro-phenyl]ethanamine (403 mg, 2.13 mmol) in THF (5 mL) was added T3P (3.17 mL, 5.33 mmol) and DIEA (2.48 mL, 14.21 mmol). The reaction was stirred at 25 °C for 1 hour. The reaction was diluted with water, extracted with ethyl acetate, washed with brine, dried over Na2SO4,filtered, and the solvent was removed under reduced pressure. The residue was purified by column chromatography to give 6-bromo-N-[(1R)-1-[3-(difluoromethyl)-2-fluoro-phenyl]ethyl]- 3H-benzotriazole-4-carboxamide (550 mg, 75% yield). LCMS (ESI): m/z: [M + H] calculated for C16H13BrF3N4O: 413.0; found 412.8;1H NMR (400 MHz, methanol-d4) δ ppm 8.23 (d, J = 33.2 Hz, 2H), 7.51 - 7.68 (m, 2H), 7.30 - 7.32 (m, 1H), 7.02 (t, J = 54.8 Hz, 1H), 5.58 - 5.63 (m, 1H), 1.68 (d, J = 7.2 Hz, 3H). |
550 mg | With 1-propanephosphonic acid cyclic anhydride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 25℃; for 1h; | 16.3 Step 3: To a solution of 6-bromo-3H-benzotriazole-4-carboxylic acid (430 mg, 1.78 mmol) and (1R)-1-[3-(difluoromethyl)-2-fluoro-phenyl]ethanamine (403 mg, 2.13 mmol) in THF (5 mL) was added T3P (3.17 mL, 5.33 mmol) and DIEA (2.48 mL, 14.21 mmol). The reaction was stirred at 25 °C for 1 hour. The reaction was diluted with water, extracted with ethyl acetate, washed with brine, dried over Na2SO4,filtered, and the solvent was removed under reduced pressure. The residue was purified by column chromatography to give 6-bromo-N-[(1R)-1-[3-(difluoromethyl)-2-fluoro-phenyl]ethyl]- 3H-benzotriazole-4-carboxamide (550 mg, 75% yield). LCMS (ESI): m/z: [M + H] calculated for C16H13BrF3N4O: 413.0; found 412.8;1H NMR (400 MHz, methanol-d4) δ ppm 8.23 (d, J = 33.2 Hz, 2H), 7.51 - 7.68 (m, 2H), 7.30 - 7.32 (m, 1H), 7.02 (t, J = 54.8 Hz, 1H), 5.58 - 5.63 (m, 1H), 1.68 (d, J = 7.2 Hz, 3H). |
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