Structure of 2315-81-3
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 2315-81-3 |
Formula : | C7H4ClNO |
M.W : | 153.57 |
SMILES Code : | OC1=C(Cl)C=C(C=C1)C#N |
MDL No. : | MFCD01567246 |
InChI Key : | CRYPJUOSZDQWJZ-UHFFFAOYSA-N |
Pubchem ID : | 2735739 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 10 |
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 | 38.19 |
TPSA ? Topological Polar Surface Area: Calculated from |
44.02 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 |
2.15 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.92 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.39 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.96 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.8 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.59 |
Solubility | 0.394 mg/ml ; 0.00257 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.71 |
Solubility | 0.302 mg/ml ; 0.00196 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.51 |
Solubility | 0.477 mg/ml ; 0.0031 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 |
-5.71 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) |
1.37 |
* 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 |
---|---|---|
In water; N,N-dimethyl-formamide; | Step A 3-Chloro-4-methoxybenzonitrile (26) Under N2, a solution of 3-chloro-4-hydroxybenzonitrile (15.4 g, 0.1 mole) in dry DMF (75 ml) was added rapidly dropwise to a stirred suspension of sodium hydride (4.0 g, 0.1 mole, 60% oil dispersion) in dry DMF (25 ml). After heating at 70 C. for 2 hours, the mixture was cooled to 20 C. and a solution of methyliodide (30 ml) in dry DMF (50 ml) was added dropwise. Following an 18 hour period at room temperature, the precipitate of sodium iodide was removed by filtration and the solvent was stripped from the filtrate under reduced pressure. The crystalline residue was slurried in water and the product was collected to yield 16.8 g (quant.) of 26, m.p. 105-108 C. | |
In water; N,N-dimethyl-formamide; | Step A: 3-Chloro-4-methoxybenzonitrile (26) Under N2, a solution of 3-chloro-4-hydroxybenzonitrile (15.4 g, 0.1 mole) in dry DMF (75 ml) was added rapidly dropwise to a stirred suspension of sodium hydride (4.0 g, 0.1 mole, 60% oil dispersion) in dry DMF (25 ml). After heating at 70 C. for 2 hours, the mixture was cooled to 20 C. and a solution of methyliodide (30 ml) in dry DMF (50 ml) was added dropwise. Following an 18 hour period at room temperature, the precipitate of sodium iodide was removed by filtration and the solvent was stripped from the filtrate under reduced pressure. The crystalline residue was slurried in water and the product was collected to yield 16.8 g (quant.) of 26, m.p. 105-108 C. | |
With potassium carbonate; In acetone; at 20℃; | Synthesis of Intermediate (1)[00334] In a 3-neck 100 mL round-bottomed flask, 3 -Chloro-5 -hydroxy benzonitrile (3.5 g, 1 eq.) was mixed with potassium carbonate (4.71 g, 1.5 eq.) using acetone (70 mL, 20 Vol.) as solvent. To this reaction mixture methyl Iodide (6.46 g, 2.0 eq.) was added drop-wise at room temperature and reaction was further stirred at RT for 3-4 h. Reaction completion was monitored on TLC using ethyl acetate: n-hexane (2:8) mobile phase. The reaction mixture was quenched into ice-water slurry (150 mL) and compound was extracted in the ethyl acetate (50 mol x 3). Organic layer was washed with brine solution (50 mol x 3) followed by drying using anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure to afford 3.5 g of crude compound, Yield (92.1 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.17 g | With boron tribromide; In dichloromethane; at -78 - 20℃; | To a solution of <strong>[102151-33-7]3-chloro-4-methoxybenzonitrile</strong> (4.25g) in DCM (85m1) was added a -78C dropwise 1M BBr3 in DCM (50.7m1). The reaction mixture was stirred at -78C for 10mm and at rt overnight. The mixture was then stirred at 40C for 4.5d and additional BBr3 sol. (26m1) was added on the first, second and third day, respectively. The reaction mixture wascarefully quenched with water, the solid precipitate was filtrated off. The layers were separated, the aq. phase was washed with DCM and the combined org. layers were dried over MgSO4, filtrated off and evaporated in vacuo. The crude was purified by CC (Buechi Sepacore, 50g cartridge, solvent A: Heptane, solvent B: EA, gradient in %B: 0 to 40, flow rate: 30 mI/mm) to afford 3.17g of a brown oil. LC-MS (A): tR = 0.68 mm; [M+H]: not visible. |
3.17 g | With boron tribromide; In dichloromethane; at -78 - 20℃;Inert atmosphere; | To a solution of <strong>[102151-33-7]3-chloro-4-methoxybenzonitrile</strong> (4.25g) in DCM (85 mL) was added a -78C dropwise 1 M sol. of BBr3 in DCM (50.7 mL). The reaction mixture was stirred at -78C for 10 min and at RT overnight. The mixture was then stirred at 40C for 4.5d and additional BBr3 sol. (26 mL) was added on the first, second and third day respectively. The reaction mixture was carefully quenched with water, the solid precipitate was filtrated off. The layers were separated, the aq. phase was washed with DCM and the combined org. layers were dried over MgS04, filtrated off and evaporated in vacuo. The crude was purified by CC (Buchi Sepacore, 50g cartridge, solvent A: Heptane , solvent B: EA, gradient in %B: 0 to 40, flow rate: 30 mL/min) to afford 3.17g of a brown oil. LC-MS (A): tR = 0.68 min; [M+H]+: not visible. |
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