Structure of 205-25-4
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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. : | 205-25-4 |
Formula : | C16H11N |
M.W : | 217.27 |
SMILES Code : | C1(NC2=C3C=CC=C2)=C3C4=CC=CC=C4C=C1 |
MDL No. : | MFCD00215940 |
InChI Key : | UGFOTZLGPPWNPY-UHFFFAOYSA-N |
Pubchem ID : | 67459 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 17 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 73.31 |
TPSA ? Topological Polar Surface Area: Calculated from |
15.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.13 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.3 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.47 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.68 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.61 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.84 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.64 |
Solubility | 0.00502 mg/ml ; 0.0000231 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.34 |
Solubility | 0.00982 mg/ml ; 0.0000452 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.64 |
Solubility | 0.0000497 mg/ml ; 0.000000229 mol/l |
Class? Solubility class: Log S scale |
Poorly 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) |
Yes |
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) |
Yes |
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 |
-4.57 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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.22 |
* 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 |
---|---|---|
87% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0℃; for 24h; | Preparation of compound 3-3 [148] After dissolving compound 3-2 (20 g, 92 mmol) in dimethylformamide (DMF) at 0C, N-bromosuccinimide (NBS) (16.3 g, 92 mmol) was slowly added to the reaction mixture and the reaction mixture was stirred for 24 hours. After completing the reaction, the organic layer was extracted EA and was dried with MgSO4 to remove the remaining moisture. The obtained organic layer was separated through column to obtain compound 3-3 (23.5 g, 87 %). |
86% | With N-Bromosuccinimide; In tetrahydrofuran; at 0 - 20℃; for 12h; | The 20.4g (0.1mol) 7H- benzo [c] carbazole was dissolved in tetrahydrofuran (THF, 500mL), and then the resulting solution was stirred at 0 10 minutes. Thereto was added N- bromosuccinimide (NBS, 18.68g, 0.105mol), the resulting mixture was stirred at normal temperature for 12 hours, then extracted with ethyl acetate and distilled water. The organic layer was dried over anhydrous magnesium sulfate (MgSO4) was dried, then the solvent was removed, and subjected to silica gel column chromatography to give 25.4g (86%) Compound B-1. |
80% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 24h; | After dissolving compound 1-9 (8.7 g, 40.1 mmol) in dimethylformamide (DMF) (50 mL), and adding N-bromosuccinimide (NBS) (4.7 g, 40.1 mmol), the reaction mixture was stirred for a day at room temperature. After terminating the reaction, the reaction mixture was extracted with EA, and the organic layer was concentrated. The resulting product was purified by a silica column to give compound 1-10 (9.5 g, 80 %). |
78% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 24h; | Preparation of Compound 7-1 [193] 7H-benzo[c]carbazole (50g, 0.23mol) was dissolved in DMF 1.4L, and NBS (41g, 0.23mol) was added, after which the mixture was stirred at room temperature for 24 hours. After termination of the reaction, the resultant mixture was extracted with EA and the organic layer was distilled under reduced pressure. Silica column separation was then performed, yielding Compound 7-1 (53.2g, 78%). |
77% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 2h;Inert atmosphere; Cooling with ice; | Under nitrogen atmosphere, N-bromosuccinimide (12.6 g) was added to a solution of 7H-benzo [c] carbazole (15.7 g) in N, N-dimethylformamide (250 mL) under ice cooling, and the temperature was raised to room temperature And the mixture was stirred for 2 hours. The resulting reaction solution was extracted with toluene, the toluene layer was washed with saturated brine, dried with anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain the objective 10-bromo-7H-benzo [c] carbazole (16.2 g, yield 77%) |
39% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 12h; | After introducing 7H-benzo[cjcarbazole (50 g, 230 mmol) and DMF (200 mL) into a flask, the mixture was stirred, and N-bromosuccinimide (42 g, 230 mmol) dissolved in DMF (50 mL) was added thereto. The resultant mixture was stirred at room temperature for 12 hours, and extracted with distilled water and MC. The obtained organic layer was dried with magnesium sulfate, and distilled under reduced pressure. The residue was purified by column chromatography to obtain compound A (10-bromo-7H-benzo[cjcarbazole) (1 6g, yield: 23.5%) |
70.8 g | With N-Bromosuccinimide; In dichloromethane; at -5 - 0℃; for 3h; | D: Add 65.1 g of benzo [c] carbazole and 600 ml of dichloromethane to a clean and dry 1000 mL four-neck reaction flask.Stir until dissolved, then cool to -5 , add 54g NBS in batches, after the addition is complete, hold the reaction at -5-0 for 3h,HPLC followed the completion of the benzo [c] carbazole reaction. After the reaction was completed, 300 ml of clear water was added to the reaction material.After stirring for a period of time, the layers were separated, the organic phase was removed, and the solvent was removed under reduced pressure to obtain a dark brown oil.450 ml of toluene and 3 g of activated carbon were added, and the mixture was stirred under reflux for 1 h, then filtered while hot, and the solvent was removed under reduced pressure from the filtrate.A pale yellow oil was obtained, 90 ml of ethanol was added, and after dissolving, crystallized at room temperature, suction filtration was performed,A white solid was obtained, 70.8 g was obtained by drying, HPLC: 99.27%, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.17 g | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; for 8h;Reflux; Inert atmosphere; | 3-bromo fluoranthene 3.10g, tris di benzylideneacetone di palladium (0) 0.18g, tri-t-butyl phosphine tetrafluoro hydro borate 0.23g, sodium-t-butoxide1.30g, dehydration xylene 100mL synthesized to the argon atmosphere, the material compound (A) 2.17g, andthe method of the wily idea was injected in the flask and it mixed reflux 8 hours heating The reacting solution was extracted in toluene to theroom temperature after doing the cooling and it filteredcellite. The filter liquor was concentrated and the residue was refined to the silica gel column chromatographyand the yellow entity 2.71g was obtained. |