Structure of 167487-83-4
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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. : | 167487-83-4 |
Formula : | C10H10N2O2 |
M.W : | 190.20 |
SMILES Code : | O=C(C1=C2NC=NC2=CC=C1)OCC |
MDL No. : | MFCD20692524 |
InChI Key : | BIROFVBTDWNLKU-UHFFFAOYSA-N |
Pubchem ID : | 13180239 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 52.18 |
TPSA ? Topological Polar Surface Area: Calculated from |
54.98 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.88 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.71 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.74 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.2 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.74 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.37 |
Solubility | 0.803 mg/ml ; 0.00422 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.48 |
Solubility | 0.629 mg/ml ; 0.00331 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.39 |
Solubility | 0.0768 mg/ml ; 0.000404 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 |
-6.25 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) |
1.63 |
* 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 |
---|---|---|
61% | Step 1: ethyl 1H-benzimidazole-4-carboxylate 2.50 g (15.4 mmol) 1H-benzimidazole-4-carboxylic acid in 100 mL ethanol are combined with 50 mL saturated ethanolic hydrochloric acid solution and refluxed for 15 hours. The reaction mixture is poured into saturated, aqueous potassium carbonate solution and extracted with ethyl acetate. The combined organic phases are dried on sodium sulphate and evaporated down to 50 mL using the rotary evaporator and filtered. 1.80 g (9.46 mmol, 61%) ethyl 1H-benzimidazole-4-carboxylate are obtained as a colourless solid. Rf=0.92 [silica gel, dichloromethane/methanol (80/20)] MS [ESI (M+H)+]]=191 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | Step 2: ethyl 1-(3-tert-butoxycarbonylamino-3-methyl-butyl)-1H-benzimidazole-4-carboxylate; 0.502 g (12.6 mmol) sodium hydride (60% in mineral oil) are added batchwise at 5 C. to 3.09 g (13.9 mmol) <strong>[167487-83-4]ethyl 1H-benzimidazole-4-carboxylate</strong> in 15 mL dimethylformamide and stirred for 30 minutes at ambient temperature. The reaction mixture is then combined with 1.75 g (9.20 mmol) tert-butyl (3-chloro-1,1-dimethyl-propyl)-carbamate and 0.310 g (0.840 mmol) tetraabutylammonium iodide and stirred for 24 hours at 60 C. The reaction mixture is poured into ice water and the aqueous phase is extracted with ethyl acetate. The combined organic phases are dried on sodium sulphate and concentrated by evaporation in the rotary evaporator. The residue is purified by reversed-phase flash column chromatography {Varian Microsorb C18-reverse-phase [acetonitrile (0.1% trifluoroacetic acid)/water (0.13% trifluoroacetic acid)=10:90?100:0], thus obtaining 0.850 g (2.26 mmol, 16%) ethyl 1-(3-tert-butoxycarbonylamino-3-methyl-butyl)-1H-benzim idazole-4-carboxylate. Rf=0.48 [silica gel, dichloromethane/methanol/ammonia (95/5/0.1)]MS [ESI (M+H)+]=376 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | Into a 100-mL round-bottom flask was placed a suspension of sodium hydride (1.24 g, 31.00 mmol, 1.20 equiv) in DMF (10 mL). Ethyl 1H-1,3-benzodiazole-4-carboxylate (4.9 g, 25.76 mmol, 1.00 equiv) was added to the reaction solution at 0 C. The resulting solution was stirred for 1 h at 0 C. Next, iodomethane (3.66 g, 25.79 mmol, 1.00 equiv) was added to the reaction mixture at 0 C. The resulting solution was allowed to react, with stirring, for an additional 2 h while the reaction mixture temperature was maintained 0 C in an ice bath. Then, the reaction was quenched by the addition of 100 mL of water. The resulting solution was extracted with 3x200 mL of dichloromethane. The combined organic layers were washed with 3x200 mL of H2O. The resulting mixture was concentrated under vacuum and the resulting residue was purified by silica gel column with dichloromethane/methanol (97:3) as eluent to furnish 2.4 g (46%) of ethyl 1-methyl-1H-1,3-benzodiazole-4-carboxylate as a red solid. |
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