Structure of 873-62-1
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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. : | 873-62-1 |
Formula : | C7H5NO |
M.W : | 119.12 |
SMILES Code : | C1=C(C=CC=C1C#N)O |
MDL No. : | MFCD00002252 |
InChI Key : | SGHBRHKBCLLVCI-UHFFFAOYSA-N |
Pubchem ID : | 13394 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 33.18 |
TPSA ? Topological Polar Surface Area: Calculated from |
44.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.2 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.7 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.26 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.79 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.34 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.26 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.14 |
Solubility | 0.857 mg/ml ; 0.0072 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.24 |
Solubility | 0.686 mg/ml ; 0.00576 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.86 |
Solubility | 1.65 mg/ml ; 0.0139 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.82 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.03 |
* 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 |
---|---|---|
22% | With bromine; acetic acid; at 20℃; for 18.0h; | Step 1 : 4-Bromo-3-cyanophenolTo a mixture of 3-cyanophenol (3.2 g, 26.8 mmol) in glacial acetic acid (20 ml) was added a solution of bromine (4.2 g, 23.3 mmol) in acetic acid (5 ml) dropwise over 5 minutes. The mixture was stirred at room temperature for 18 hours. The mixture was filtered. The filtrate was added to water (100 ml) containing a few mg of sodium thiosulfate. The insoluble material was collected and the filter cake was added to warm methanol (15 ml) and was filtered through celite. The filtrate was slowly diluted with water and the precipitate was collected and dried to give the title compound, 183-5C, mp (1.0 g, 22%). |
With N-Bromosuccinimide; tetrafluoroboric acid diethyl ether complex; In acetonitrile; at -20 - 20℃; for 5.0h; | 3-Hydroxybenzonitrile (2. 0g, 16. [8MMOL)] was dissolved in acetonitrile [(20ML)] and cooled [TO-20C.] [TETRAFLUOROBORIC] acid diethyl ether complex (2. [3ML,] 16. [8MMOL)] followed by N- bromosuccinimide (3. 0g, 16. [8MMOL)] were added and the mixture allowed to warm to ambient temperature. The resulting mixture was stirred for 5 hours, treated with aqueous sodium hydrogen sulfate solution (38%, [10MI)] and extracted with methyl 2-methylpropyl ether (x2). The organic extracts were combined, washed with water (x2) and brine, dried under magnesium sulphate and evaporated in vacuo. The residue was purified by silica gel chromatography eluting with a mixture of methyl 2-methylpropyl ether/dichloromethane (2: 98) to give the title compound (1.58g). MS (ES+) m/e 197 [M- [H]] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With potassium carbonate; In N,N-dimethyl-formamide; at 130℃; for 1h;Microwave irradiation; | Tert-butyl 4-(3-cyanophenoxy)benzoate. To the solution of tert-butyl 4- fluorobenzoate (500 mg, 2.55 mmol) and 3-hydroxybenzonitrile (306 mg, 2.55 mmol) in N,N- dimethylformamide(80 mL) was added potassium carbonate (528 mg, 3.8 mmol), the mixture was stirred at 130 C for 1 hour under microwave. Then evaporated the solvent purified by column chromatography (silica gel, Petroleum ether / ethyl acetate = 10: 1) to give tert-butyl4- (3-cyanophenoxy)benzoate (185 mg, 57%), as oil, 1H-NMR (300 MHz, CD3OD) delta 8.00(m, 2H), 7.56 (m, 2H), 7.43 (m ,2H), 7.05 (m, 2H), 1.59(s, 9H). |
57% | With potassium carbonate; In N,N-dimethyl-formamide; at 130℃; for 1h;Microwave irradiation; | To the solution of <strong>[58656-98-7]ter<strong>[58656-98-7]t-butyl 4-fluorobenzoate</strong></strong> (500 mg, 2.55 mmol) and 3-hydroxybenzonitrile (306 mg, 2.55 mmol) in N,N-dimethylformamide (80 mL) was added potassium carbonate (528 mg, 3.8 mmol), the mixture was stirred at 130 C. for 1 hour under microwave. Then evaporated the solvent purified by column chromatography (silica gel, Petroleum ether/ethyl acetate=10:1) to give tert-butyl-4-(3-cyanophenoxy)benzoate (185 mg, 57%), as oil, 1H-NMR (300 MHz, CD3OD) delta 8.00 (m, 2H), 7.56 (m, 2H), 7.43 (m, 2H), 7.05 (m, 2H), 1.59 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With caesium carbonate; In N,N-dimethyl-formamide; at 120℃; for 1h; | Step 1)3-(3- Chloro-4-nitro-phenoxy)-benzonitrile A mixture of <strong>[2106-50-5]2-chloro-4-fluoro-1-nitro-benzene</strong> (15 g, 85 mmol), 3-hydroxybenzonitrile (10.1 g,85 mmol) and Cs2CO3 (30.4 g, 93.5 mmol) in DMF (100 mL) was heated at 120 C for 1 h.EtOAc was added and the mixture was washed with water and brine. The organic layer was dried(Na2SO4), filtered, and evaporated to give 3-(3-chloro-4-nitro-phenoxy)-benzonitrile (23 g, 99%)as a yellow solid. |
99% | With caesium carbonate; In N,N-dimethyl-formamide; at 120℃; for 1h; | A mixture of <strong>[2106-50-5]2-chloro-4-fluoro-1-nitro-benzene</strong> (15 g, 85 mmol), 3-hydroxybenzonitrile (10.1 g, 85 mmol) and Cs2CO3 (30.4 g, 93.5 mmol) in DMF (100 mL) was heated at 120 C for 1 h.EtOAc was added and the mixture was washed with water and brine. The organic layer was dried (Na2SO4), filtered, and evaporated to give 3-(3-chloro-4-nitro-phenoxy)-benzonitrile (23 g, 99%) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 12h; | Methyl 4-(1-hydroxyethyl)benzoate (540 mg, 3 mmol), 3-hydroxybenzonitrile (360 mg, 3 mmol), triphenylphosphine (1.04 mg, 4 mmol), azodicarboxylic acid diisopropyl ester (800 mg, 4 mmol) in tetrahydrofuran (130 mL) were stirred at 20 C. for 12 hours. Water was added and the mixture was extracted with ethyl acetate (150 mL×3), the combined organic phase was dried by sodium sulfate, then filtered. The filtrate was evaporated in vacuum and the residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=3:1) to give methyl 4-(1-(4-cyanophenoxy)ethyl)benzoate (370 mg, 45%) as colorless oil. LRMS (M+H+) m/z: calcd 281.11. found 281. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1 g | With caesium carbonate; In N,N-dimethyl-formamide; at 60℃; for 17h; | To a suspension of compound B5 (4.00 g, 25.2 mmol) and Cs2C03 (16.4 g, 50.5 mmol) in DMF (50 mL) was added 3-cyanophenol (3.16 g, 26.5 mmol), the mixture was stirred at 60C for 17 hours to give a brown suspension. Crude LCMS (RT: 1.384 min) showed the reaction was completed. The mixture was poured into water (400 mL), a lot of white solid appeared, filtered, the filter cake was washed with water (30 mL x 3) to give the crude product. The crude product was purified by Combi flash to give 1.00 g of compound B6 as a yellow powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | Dissolve phenyl dichlorophosphate (4.9 g, 23.2 mmol) in 200 mL of DCM,Add <strong>[14019-62-6]glycine isopropyl ester hydrochloride</strong> (3.2g, 20.8mmol) and lower the temperature to -20 C.Triethylamine (6.4 g, 63.2 mmol) was added, and after stirring for 20 min, 6A (2.5 g, 20.8 mmol) was added, and the temperature was slowly raised to room temperature and stirred for 20 min.The reaction solution was washed with 200 ml of a saturated disodium hydrogen phosphate solution and 200 ml of a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure.The residue was further purified by silica gel column chromatography (ethyl acetate / petroleum ether = (v / v) 1/3 to 1/1) to obtain the target compound 14B as a pale yellow oil (2g, 25% yield). |
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