 
                                
                                 
                                
                                
                                    Structure of 9CAA
                                    
                                    
CAS No.: 524-80-1
                                    
                                
 
                                 
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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. : | 524-80-1 | 
| Formula : | C14H11NO2 | 
| M.W : | 225.24 | 
| SMILES Code : | O=C(O)CN1C2=C(C3=C1C=CC=C3)C=CC=C2 | 
| MDL No. : | MFCD00439433 | 
| InChI Key : | PBDMLLFEZXXJNE-UHFFFAOYSA-N | 
| Pubchem ID : | 2815870 | 
| GHS Pictogram: |   | 
| Signal Word: | Warning | 
| Hazard Statements: | H302-H315-H319-H335 | 
| Precautionary Statements: | P261-P305+P351+P338 | 
| Num. heavy atoms | 17 | 
| Num. arom. heavy atoms | 13 | 
| Fraction Csp3 | 0.07 | 
| Num. rotatable bonds | 2 | 
| Num. H-bond acceptors | 2.0 | 
| Num. H-bond donors | 1.0 | 
| Molar Refractivity | 67.28 | 
| TPSA ? Topological Polar Surface Area: Calculated from  | 42.23 Ų | 
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from  | 1.61 | 
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by  | 3.88 | 
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from  | 2.88 | 
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from  | 2.29 | 
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by  | 2.24 | 
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 2.58 | 
| Log S (ESOL):? ESOL: Topological method implemented from  | -4.11 | 
| Solubility | 0.0173 mg/ml ; 0.0000768 mol/l | 
| Class? Solubility class: Log S scale  | Moderately soluble | 
| Log S (Ali)? Ali: Topological method implemented from  | -4.46 | 
| Solubility | 0.00773 mg/ml ; 0.0000343 mol/l | 
| Class? Solubility class: Log S scale  | Moderately soluble | 
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by  | -3.92 | 
| Solubility | 0.0271 mg/ml ; 0.000121 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) | No | 
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from  | -4.92 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  | 0.0 | 
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat  | 0.56 | 
| 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<2.0 | 
| Synthetic accessibility? Synthetic accessibility score:  from 1 (very easy) to 10 (very difficult) | 1.58 | 
* 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 | 
|---|---|---|
| 80% | With oxalyl dichloride; In benzene; at 35℃; for 6.0h;Inert atmosphere; | To a solution of 5 g (0.022 mol) e in 50 mL of dried benzene, 3.8 g (0.03 mol) oxalyl chloride was added dropwise. The mixture was stirred at 35 C for 6 h under N2 atmosphere. After completion of the reaction, the mixture was concentrated, then crystallized with dried petroleum ether. Pure product was obtained as white crystals, 4.3 g. Yield: 80%. 1H NMR (CDCl3, 400 MHz, delta ppm): 8.14 (d, 2H, J=7.8 Hz), 7.53 (m, 2H), 7.35 (m, 4H), 5.41 (s, 2H). 13C NMR (CDCl3, 100 MHz, delta ppm): 170.1, 139.8, 126.3, 123.5, 120.6, 120.5, 108.1, 53.6. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 90% | In N,N-dimethyl-formamide; at 35℃; for 12.0h; | To a solution of 5 g (0.03 mol) carbazole in 100 mL of DMF, 6.68 g (0.04 mol) ethyl bromoacetate was added. The mixture was stirred at 35 C for 12 h, then poured into 200 mL water, filtered. The pH of filtrate was adjusted to 1.0 with 2 M hydrochloric acid. Crude product was obtained by filtration, then dried. White crystals were obtained after crystallization (CH2Cl2/ethanol), 6.1 g. Yield: 90%. 1H NMR (CDCl3, 400 MHz, delta ppm): 13.10 (s, 1H), 8.16 (d, 2H, J=7.8 Hz), 7.55 (m, 2H), 7.42 (m, 2H), 7.22 (m, 2H), 5.23 (s, 2H). 13C NMR (DMSO-d6, 100 MHz, delta ppm): 170.2, 140.4, 125.6, 122.2, 120.1, 119.0, 109.2, 43.9. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| EXAMPLE 87 2-(N-Carbazolyl)acetic acid The title compound is prepared as per Example 63 using carbazole as the starting heterocycle. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 87% | With triethylamine; N,N-dimethyl-formamide; at 25℃;pH 8; | To a dry 250 mL three-necked flask was added 0.005 mol of carbazole, 0.005 mol of potassium chloroacetate, 0.05 mol of N, N-dimethylformamide;The flask was heated and triethylamine was added dropwise to adjust the pH to 8, heated to 25 C and stirred while TLC was monitored, and the developing agent used for TLC monitoring was ethyl acetate and petroleum ether in volume ratio Mix the solution after 1: 3;After monitoring the reaction, the three-necked flask was cooled to room temperature and the pH of the solution in the flask was adjusted to 2 by the addition of concentrated HCl.The solution obtained in Step 3) is poured into water, and after the white solid has been precipitated, it is subjected to suction filtration, washed and dried;The dried product was recrystallized using an absolute ethanol solution to give N-carboxymethylcarbazole.yield were 87%, | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 75.2% | With trichlorophosphate;Reflux; | In a dry three-necked flask,Add 1 g (4.4 mmol) of 9-carbazole acetic acid toAnd 0.58g (4.4mmol) 3- amino-5-methyl-mercapto-triazole,Add 20 mL of POCl3 and stir until completely dissolved.Warming to reflux reaction, TLC monitoring until the end of the reaction;The reaction solution was cooled to room temperature, poured into crushed ice and stirred well.Adjust the pH to 8-9 with a certain mass fraction of NaOH solution, precipitate solids, suction filtration, recrystallization,Dry to pale yellow solid (containing oxazolyl triazolothiadiazole),The yield was 75.2%. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 76.3% | With trichlorophosphate;Reflux; | In a dry three-necked flask,Add 1 g (4.4 mmol) of 9-carbazole acetic acid toAnd 0.64g (4.4mmol) 3- mercapto-4-amino-5-methylphenyl triazolo,Add 20 mL of POCl3 and stir until completely dissolved.Warming to reflux reaction, TLC monitoring until the end of the reaction;The reaction solution was naturally cooled to room temperature, poured into crushed ice and stirred well.Adjust the pH to 8-9 with a certain mass fraction of NaOH solution,Static precipitation, suction filtration, recrystallization,Dry to pale yellow solid (containing oxazolyl triazolothiadiazole),The yield was 76.3%. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 71.8% | With trichlorophosphate;Reflux; | In a dry three-necked flask,Add 1 g (4.4 mmol) of 9-carbazole acetic acid toAnd 0.92g (4.4mmol) 3- mercapto-4-amino-5-ethyl-triazole,Add 20 mL of POCl3 and stir until completely dissolved.Warming to reflux reaction, TLC monitoring until the end of the reaction;The reaction solution was naturally cooled to room temperature, poured into crushed ice and stirred well.Use a certain mass fraction of NaOH solution to adjust the pH to 8-9, static precipitation, suction filtration, recrystallization,Dry to pale yellow solid (containing carbazolyl triazolothiadiazole) in a yield of 71.8%. |