Structure of 25173-76-6
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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. : | 25173-76-6 |
Formula : | C11H14O2 |
M.W : | 178.23 |
SMILES Code : | O=C(O)CCC1=CC=C(C)C(C)=C1 |
MDL No. : | MFCD03425686 |
Boiling Point : | No data available |
InChI Key : | FHEOAGCWJWUKJJ-UHFFFAOYSA-N |
Pubchem ID : | 3870218 |
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 | 6 |
Fraction Csp3 | 0.36 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 52.73 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.89 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.46 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.32 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.58 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.86 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.62 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.27 |
Solubility | 0.0961 mg/ml ; 0.000539 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.92 |
Solubility | 0.0212 mg/ml ; 0.000119 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.35 |
Solubility | 0.0791 mg/ml ; 0.000444 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 |
-4.93 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 |
0.56 |
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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.13 |
* 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 |
---|---|---|
98% | With hydrogen In methanol at 20℃; for 4 h; | A mixture of 3-(3,4-dimethyl-phenyl)-acrylic acid (19.269 g; 109.355 mmol) and 10percent palladium over activated charcoal (1.920 g) was placed under nitrogen before methanol (300 ml) was carefully added. The resulting suspension was placed under vacuum, then under hydrogen (1 atm), and the reaction mixture was vigorously stirred at rt for 4h. The reaction mixture was filtered over a pad of celite, and concentrated under reduced pressure to give the expected product 3- (3,4-dimethyl-phenyl)-propionic acid as a grey solid which was further dried under HV (19.070 g; 98percent). LC-MS: tR = 0.85 min; [M+H]+: no ionisation. |
98% | With hydrogen In methanol at 20℃; for 4 h; | A mixture of 3-(3,4-dimethyl-phenyl)-acrylic acid (19.269 g; 109.355 mmol) and 10percent palladium over activated charcoal (1.920 g) was placed under nitrogen before MeOH (300 ml) was carefully added. The resulting suspension was placed under vacuum, then under hydrogen (1 atm), and the reaction mixture was vigorously stirred at rt for 4h. The reaction mixture was filtered over a pad of celite, and concentrated under reduced pressure to give the expected product 3-(3,4-dimethyl-phenyl)-propionic acid as a grey solid which was further dried under HV (19.070 g; 98percent). LC-MS: tR = 0.85 min; [M+H]+: no ionisation. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With potassium hydroxide; sulfuric acid In diethyl ether; ethanol; water | Step 1) Synthesis of 3-(3,4-dimethylphenyl)propionic acid To a solution of 70.0 ml of diethyl malonate dissolved in 400 ml of dry ethanol was added 10.0 g of metallic sodium. The reaction mixture was stirred for 30 minutes and cooled to 0° C; and 66.5 g of 3,4-dimethylbenzyl chloride was added thereto. This reaction mixture was stirred at a room temperature for another 1 hour, heated at the boiling temperature for 4 hours and concentrated under a reduced pressure. The residue was dissolved in ethyl ether and the solution was washed with water. After further concentration under a reduced pressure, the organic phase was combined with 500 ml of water and 170 g of KOH; and this mixture was heated at the boiling temperature for 24 hours. The mixture was concentrated under a reduced pressure to about one half volume; then 200 ml of 98percent sulfuric acid was added slowly thereto. The resultant solution was heated at the boiling temperature for 24 hours, extracted twice with 300 ml of ethyl acetate. The organic solvent was distilled off under a reduced pressure and the residue was recrystallized from boiling hexane to obtain 42.1 g of the title compound as a white solid(yield: 55percent). m.p.: 82° C. 1 H-NMR(300 MHz, CDCl3) δ2.22(s, 3H, CH3), 2.24(s, 3H, CH3), 2.66(t, J=8 Hz, 2H, ArCH2), 2.89(t, J=8 Hz, 2H, CH2 CO), 6.93-7.70(m, 3H, ArH) |
55% | With potassium hydroxide; sulfuric acid In diethyl ether; ethanol; water | Step 1) Synthesis of 3-(3,4-dimethylphenyl)propionic acid To a solution of 70.0ml of diethyl malonate dissolved in 400ml of dry ethanol was added 10.0g of metallic sodium. The reaction mixture was stirred for 30 minutes and cooled to 0°C; and 66.5g of 3,4-dimethylbenzyl chloride was added thereto. This reaction mixture was stirred at a room temperature for another 1 hour, heated at the boiling temperature for 4 hours and concentrated under a reduced pressure. The residue was dissolved in ethyl ether and the solution was washed with water. After further concentration under a reduced pressure, the organic phase was combined with 500ml of water and 170g of KOH; and this mixture was heated at the boiling temperature for 24 hours. The mixture was concentrated under a reduced pressure to about one half volume; then 200ml of 98percent sulfuric acid was added slowly thereto. The resultant solution was heated at the boiling temperature for 24 hours, extracted twice with 300ml of ethyl acetate. The organic solvent was distilled off under a reduced pressure and the residue was recrystallized from boiling hexane to obtain 42.lg of the title compound as a white solid(yield: 55percent). m.p.: 82°C 1H NMR(300MHz, CDCl3) δ 2.22(s, 3H, CH3), 2.24(s, 3H, CH3), 2.66(t, J=8Hz, 2H, ArCH2), 2.89(t, J=8Hz, 2H, CH2CO), 6.93-7.70(m, 3H, ArH) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With potassium hydroxide; sulfuric acid In diethyl ether; ethanol; water | PREPARATION EXAMPLE 1 Synthesis of 3-(3,4-dimethylphenyl)propylamine To a solution of 70.0 ml of diethyl malonate dissolved in 400 ml of dry ethanol was added 10.0 g of metalic sodium. The reaction mixture was stirred for 30 minutes and cooled to 0° C; and 66.5 g of 3,4-dimethylbenzyl chloride was added thereto. This reaction mixture was stirred for 1 hour at room temperature, heated at the boiling temperature for 4 hours and concentrated under reduced pressure to produce residues, which were dissolved in ethyl ether. This ethereal solution was washed with water. To the residues obtained after a further concentration of the organic phase were added 500 ml of water and 170 g of KOH; and this mixture was heated at the boiling temperature for 24 hours. This mixture was concentrated under reduced pressure until about a half of the amount remained, and 200 ml of sulfuric acid was then slowly added thereto. The resultant solution was heated at the boiling temperature for 24 hours, extracted twice with 300 ml of ethyl ether and evaporated under reduced pressure to obtain solids, which were recrystallized from boiling hexane to provide 42.1 g of 3-(3,4-dimethylphenyl)propanoic acid as a white solid (yield 55percent), having the characteristics of: m.p. 82° C.; NMR(CDCl3, 300 MHz) δ2.22(s, 3H, CH3), 2.24(s, 3H, CH3), 2.66(t, J=8 Hz, 2H, ArCH2), 2.89(t, J=8 Hz, 2H, CH2 CO), 6.93~7.70(m, 3H, ArH). |
55% | With potassium hydroxide; sulfuric acid In diethyl ether; ethanol | Preparation Example 1: Synthesis of 3-(3,4-dimethylphenyl)propylamine To a solution of 70.0m of diethyl malonate dissolved in 400m of dry ethanol was added 10.0g of metalic sodium. The reaction mixture was stirred for 30 minutes and cooled to 0°C; and 66.5g of 3,4-dimethylbenzyl chloride was added thereto. This reaction mixture was stirred for 1 hour at room temperature, heated at the boiling temperature for 4 hours and concentrated under reduced pressure to produce residues, which were dissolved in ethyl ether. This ethereal solution was washed with water. To the residues obtained after a further concentration of the organic phase were added 500m of water and 170g of KOH; and this mixture was heated at the boiling temperature for 24 hours. This mixture was concentrated under reduced pressure until about a half of the amount remained, and 200m of sulfuric acid was then slowly added thereto. The resultant solution was heated at the boiling temperature for 24 hours, extracted twice with 300m of ethyl ether and evaporated under reduced pressure to obtain solids, which were recrystallized from boiling hexane to provide 42.1g of 3-(3,4-dimethylphenyl)propanoic acid as a white solid(yield 55percent), having the characteristics of: m.p. 82°C; NMR(CDCl3, 300MHz)δ 2.22(s, 3H, CH3), 2.24(s, 3H, CH3), 2.66(t, J=8Hz, 2H, ArCH2), 2.89(t, J=8Hz, 2H, CH2CO), 6.93~7.70(m, 3H, ArH). |
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