Structure of 223576-64-5
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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. : | 223576-64-5 |
Formula : | C8H6BClO3 |
M.W : | 196.40 |
SMILES Code : | ClC1=CC=C(OC(B(O)O)=C2)C2=C1 |
MDL No. : | MFCD18383028 |
InChI Key : | IODPQZJZPKMFKV-UHFFFAOYSA-N |
Pubchem ID : | 18476279 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 51.05 |
TPSA ? Topological Polar Surface Area: Calculated from |
53.6 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.89 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.77 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.35 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.4 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.68 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.69 |
Solubility | 0.397 mg/ml ; 0.00202 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.64 |
Solubility | 0.452 mg/ml ; 0.0023 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.8 |
Solubility | 0.313 mg/ml ; 0.00159 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) |
No |
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 |
-6.16 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 |
1.0 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) |
2.71 |
* 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 |
---|---|---|
83% | Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In hexane; Dimethyl ether at -60 - -10℃; for 1.25 h; Stage #2: With Triisopropyl borate In hexane; Dimethyl ether at -60℃; Stage #3: With hydrogenchloride In hexane; Dimethyl ether; water for 1 h; |
5-Chlorobenzofuran was prepared by heating 4-chlorophenoxyacetaldehyde dimethylacetal in polyphosphoric acid; yield: 73percent. [0323] To a solution of 8.8 g (57.7 mmol) 5-chlorobenzofuran in 250 ml dry ether were added 7.32 g (63.0 mmol) tetramethylethylenediamine (TMEDA). The solution was kept below -60° C. under argon, while 37.5 ml of a 1.6M solution of butyllithium in hexane was added dropwise. It was warmed to -10° C. during 45 min and stirred at this temperature for another 30 min. The mixture was cooled again below -60° C. followed by dropwise addition of 35.7 g (190 mmol) triisopropyl borate. After warming to room temperature the mixture was quenched with 70 ml 2N hydrochloric acid and stirred for 1 h. The organic layer was washed three times with 30 ml 2N hydrochloric acid, twice with water, and extracted with 2N sodium hydroxide solution, successively. The alkaline aqueous layer was brought to pH5 and extracted with tert.-butylmethylether. All organic layers were combined, dried over sodium sulfate, and concentrated in vacuo to give the pale yellow crystalline boronic acid which was used for the next step without further purification. [0324] yield: 9.4 g (83percent); MS 196 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With hydrogenchloride; n-butyllithium In PPA; hexane | Step A: 5-Chlorobenzofuran-2-boronic acid 5-Chlorobenzofuran was prepared by heating 4-chlorophenoxyacetaldehyde dimethylacetal in polyphosphoric acid; yield: 73percent. To a solution of 8.8 g (57.7 mmol) 5-chlorobenzofuran in 250 ml dry ether were added 7.32 g (63.0 mmol) tetramethylethylenediamine (TMEDA). The solution was kept below -60° C. under argon, while 37.5 ml of a 1.6M solution of butyllithium in hexane was added dropwise. It was warmed to -10° C. during 45 min and stirred at this temperature for another 30 min. The mixture was cooled again below -60° C. followed by dropwise addition of 35.7 g (190 mmol) triisopropyl borate. After warming to room temperature the mixture was quenched with 70 ml 2N hydrochloric acid and stirred for 1 h. The organic layer was washed three times with 30 ml 2N hydrochloric acid, twice with water, and extracted with 2N sodium hydroxide solution, successively. The alkaline aqueous layer was brought to pH5 and extracted with tert.-butylmethylether. All organic layers were combined, dried over sodium sulfate, and concentrated in vacuo to give the pale yellow crystalline boronic acid which was used for the next step without further purification. yield: 9.4 g (83percent); MS 196 (M+). |
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