Structure of 136450-06-1
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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. : | 136450-06-1 |
Formula : | C25H25NO4 |
M.W : | 403.47 |
SMILES Code : | CC(=O)C1=CC=CC(NC(=O)C2=CC=C(OCCCCC3=CC=CC=C3)C=C2)=C1O |
MDL No. : | MFCD09835307 |
InChI Key : | NTUBQTVFDLDHRH-UHFFFAOYSA-N |
Pubchem ID : | 60836 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 30 |
Num. arom. heavy atoms | 18 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 10 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 118.27 |
TPSA ? Topological Polar Surface Area: Calculated from |
75.63 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.89 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.28 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.06 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.47 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.27 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.59 |
Log S (ESOL):? ESOL: Topological method implemented from |
-5.45 |
Solubility | 0.00143 mg/ml ; 0.00000353 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-6.62 |
Solubility | 0.0000971 mg/ml ; 0.000000241 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-8.47 |
Solubility | 0.00000136 mg/ml ; 0.0000000034 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 |
No |
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) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
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 |
-5.01 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<3.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.74 |
* 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 |
---|---|---|
With sodium carbonate; In toluene; | (3) In a reactor, toluene (160 g) and 3-amino-2-hydroxyacetophenone (hereinafter referred to as "AHA") sulfate (the molecular weight, 249.3. 42.3 g) were charged and heated to 40 C. At the same temperature, to this solution, the solution of 4-(4-phenyl-1-butoxy)benzoyl chloride in toluene (79.3 g) obtained in the above step (2) and an aqueous solution of sodium carbonate (1.6 equivalents to <strong>[30131-16-9]4-(4-phenyl-1-butoxy)benzoic acid</strong>) were dropwise added simultaneously over a period of one hour, followed by heating at the same temperature for 2 hours. After the completion of the reaction, the reaction mixture was neutralized with hydrochloric acid. An organic layer was washed with water and phase separated. Then, the organic layer was cooled to 0 C. and maintained at that temperature to crystallize the product to obtain 3-[4-(4-phenyl-1-butoxy)benzoyl]amino-2-hydroxyacetophenone (66.8 g). Yield of the pure product, 97.3% (based on AHA sulfate). | |
With sodium carbonate; In toluene; | (3) In a reactor, toluene (80 g) and AHA hydrochloride (the molecular weight, 187.6. 15.9 g) were charged and heated to 40 C. At the same temperature, to this solution, the solution of 4-(4-phenyl-1-butoxy)benzoyl chloride in toluene (41.1 g) obtained in the above step (2) and an aqueous solution of sodium carbonate (1.2 equivalents to <strong>[30131-16-9]4-(4-phenyl-1-butoxy)benzoic acid</strong>) were dropwise added simultaneously over a period of one hour, followed by heating at the same temperature for 2 hours. After the completion of the reaction, the reaction mixture was neutralized with hydrochloric acid. An organic layer was washed with water and phase separated. Then, the organic layer was cooled to 0 C. and maintained at that temperature to crystallize the product to obtain 3-[4-(4-phenyl-1-butoxy)benzoyl]amino-2-hydroxyacetophenone (33.4 g). Yield of the pure product, 96.9% (based on AHA hydrochloride). | |
With sodium carbonate; In toluene; | (3) In a reactor, toluene (80 g) and AHA sulfate (21.3 g) were charged and heated to 40 C. At the same temperature, to this solution, the solution of 4-(4-phenyl-1-butoxy)benzoyl chloride in toluene (40.7 g) obtained in the above step (2) and an aqueous solution of sodium carbonate (1.6 equivalents to <strong>[30131-16-9]4-(4-phenyl-1-butoxy)benzoic acid</strong>) were dropwise added simultaneously over a period of one hour, followed by heating at the same temperature for 2 hours. After the completion of the reaction, the reaction mixture was neutralized with hydrochloric acid. An organic layer was washed with water and phase separated. Then, the organic layer was cooled to 0 C. and maintained at that temperature to crystallize the product to obtain 3-[4-(4-phenyl-1-butoxy)benzoyl]amino-2-hydroxyacetophenone (33.6 g). Yield of the pure product, 95.2% (based on <strong>[30131-16-9]4-(4-phenyl-1-butoxy)benzoic acid</strong>). |
With sodium carbonate; In toluene; | (3) In a reactor, toluene (80 g) and AHA hydrochloride (16.0 g) were charged and heated to 40 C. At the same temperature, to this solution, the solution of 4-(4-phenyl-1-butoxy)benzoyl chloride in toluene (41.4 g) obtained in the above step (2) and an aqueous solution of sodium carbonate (1.3 equivalents to <strong>[30131-16-9]4-(4-phenyl-1-butoxy)benzoic acid</strong>) were dropwise added simultaneously over a period of one hour, followed by heating at the same temperature for 2 hours. After the completion of the reaction, the reaction mixture was neutralized with hydrochloric acid. An organic layer was washed with water and phase separated. Then, the organic layer was cooled to 0 C. and maintained at that temperature to crystallize the product to obtain 3-[4-(4-phenyl-1-butoxy)benzoyl]amino-2-hydroxyacetophenone (32.1 g). Yield of the pure product, 93.3% (based on AHA hydrochloride). | |
With sodium carbonate; In toluene; | (3) In a reactor, toluene (162.0 g) and AHA sulfate (43.3 g) were charged and heated to 45 C. At the same temperature, to this solution, the solution of 4-(4-phenyl-1-butoxy)benzoyl chloride in toluene (146.5 g) obtained in the above step (2) and an aqueous solution of sodium carbonate (1.6 equivalents to <strong>[30131-16-9]4-(4-phenyl-1-butoxy)benzoic acid</strong>) were dropwise added simultaneously over a period of one hour, followed by heating at the same temperature for 2 hours. After the completion of the reaction, the reaction mixture was neutralized with hydrochloric acid. An organic layer was washed with water and separated. Then, the organic layer was cooled to 0 C. and maintained at that temperature to crystallize the product to obtain 3-[4-(4-phenyl-1-butoxy)benzoyl]amino-2-hydroxyacetophenone (68.8 g). Yield of the pure product, 96.7% (from the step (2), based on <strong>[30131-16-9]4-(4-phenyl-1-butoxy)benzoic acid</strong>). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | 270 g of 4- (phenylbutoxy) benzoic acid was added, 270 g of thionyl chloride was added and incubated at 50 C for 3 hours. After completion of the reaction, the unreacted thionyl chloride was recovered under reduced pressure. Nitrogen blowing into the thiophene chloride. Cooled to room temperature by adding 270 g of dichloromethane. Weigh 151 g of 3-amino-2-hydroxyacetophenone in 200 g of methylene chloride, 160 g of pyridine was added, and a solution of 4- (phenylbutoxy) benzoyl chloride in methylene chloride was added dropwise to the ice bath. The temperature is not more than 10 , dripping finished, 10 incubation reaction 2h, after the end of the reaction, adding to the reaction system dilute hydrochloric acid, adjust the pH to 2-3, liquid, methyl chloride layer washed to neutral, anhydrous Dried over sodium sulfate, filtered and concentrated to give a reddish brown solid, petroleum ether: ethyl acetate = 1: 1 recrystallization to give 334 g, yield 84%. |
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