Structure of 59662-46-3
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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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CAS No. : | 59662-46-3 |
Formula : | C17H18O2 |
M.W : | 254.32 |
SMILES Code : | CCCCC1=CC=C(C=C1)C1=CC=C(C=C1)C(O)=O |
MDL No. : | MFCD00222812 |
Boiling Point : | No data available |
InChI Key : | BVBTVBVHIQDKKW-UHFFFAOYSA-N |
Pubchem ID : | 2757304 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 19 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.24 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 78.22 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.76 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.6 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.39 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.16 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.51 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.29 |
Log S (ESOL):? ESOL: Topological method implemented from |
-5.08 |
Solubility | 0.0021 mg/ml ; 0.00000828 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-6.15 |
Solubility | 0.000182 mg/ml ; 0.000000715 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.89 |
Solubility | 0.000325 mg/ml ; 0.00000128 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
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) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-3.88 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
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) |
1.8 |
* 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 |
---|---|---|
There are prepared analogously: 4-(4-ethylphenyl)-benzoic acid, 4-(4-n-propylphenyl)-benzoic acid, 4-(4-n-butylphenyl)-benzoic acid, 4-(4-n-hexylphenyl)-benzoic acid, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.1% | With water; sodium hydroxide; In tetrahydrofuran;Reflux; | [00269] General Method 13: The synthesis of a biaryl or aryl-heteroaryl carboxylic acid from l-bromo-4-butylbenzene and an aryl- or heteroaryl boronic acid. An illustration of this method is depicted for 4-(4-butylphenyl)benzoic acid. [00271] A mixture of methyl 4-(4-butylphenyl)benzoate (89.0 g, 0.332 mol), NaOH (26.6 g, 0.664 mol) in THF/H20 (500 mL/100 mL) was heated to reflux overnight. After TLC showed the reaction was complete, THF was removed. The residue was adjusted pH -3-4 with 2 N HC1 solution. The resulting mixture was filtered and the cake was washed with water, dried to give 4-(4-butylphenyl)benzoic acid (60.0 g, yield: 71.1%), as a white solid. (ESI) m/z 255.0 (M + H)+. |
71.1% | With water; sodium hydroxide; In tetrahydrofuran; | A mixture of methyl 4?-butyl-[1,1?-biphenylj-4-carboxylate (89.0 g, 0.332mol), NaOH (26.6 g, 0.664 mol) in THF/H20 (500 mL/100 mL) was heated to reflux overnight.After TLC showed the reaction was complete, THF was removed. The residue was adjusted pH=34 with 2 N HC1 solution. The resulting mixture was filtered and the cake was washed with water, and dried to give 4?-butyl-[1,1?-biphenylj-4-carboxylic acid (60.0 g, 71.1%) as a white solid. |
71.1% | With sodium hydroxide; In tetrahydrofuran; water;Reflux; | A mixture of methyl 4?-butyl-[1,1?-biphenylj-4-carboxylate (89.0 g, 0.332 mol), NaOH (26.6 g, 0.664 mol) in THF/H20 (500 mL/100 mL) was heated to reflux overnight. After TLC showed the reaction was complete, THF was removed. The residue was adjusted pH=34 with 2 N HC1 solution. The resulting mixture was filtered and the cake was washed with water, and dried to give 4?-butyl- [1,1 ?-biphenylj -4-carboxylic acid (60.0 g, 71.1%) as a white solid. |
With hydrogenchloride; In water; | A mixture of methyl 4-(4-butylphenyl)benzoate (89.0 g, 0.332 mol), NaOH (26.6 g, 0.664 mol) in THF/H2O (500 mL/100 mL) was heated to reflux overnight. After TLC showed the reaction was complete, THF was removed. The residue was adjusted pH ?3-4 with 2 N HCl solution. The resulting mixture was filtered and the cake was washed with water, dried to give 4-(4-butylphenyl)benzoic acid (60.0 g, yield: 71.1%), as a white solid. (ESI) m/z 255.0 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54.4% | With sodium hydrogencarbonate; HATU; In tetrahydrofuran; N,N-dimethyl-formamide; at 25℃; for 5h; | [00351] To a solution of Compound 278A1 (1.00 g, 2.39 mmol), 4-(4- butylphenyl)benzoic acid (0.728 g, 2.89 mmol) and NaHC03 (0.742 g, 8.84 mmol) in dry THF (30 mL) and DMF (30 mL) was added HATU (1.09 g, 2.89 mmol). The mixture was stirred at 25 C until LCMS indicated the reaction was finished (5 hrs). THF was evaporated and the mixture was poured into water (100 mL) and extracted with DCM (80 mL x 2). The combined organic layers were evaporated and purified by silica-gel column chromatography to give Compound 278A2 (800 mg, yield: 54.4 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[00243] A mixture of <strong>[59662-46-3]4-(4-butylphenyl)benzoic acid</strong> (1.5 eq), HCTU (1.5 eq), HOBT (1.5 eq) and DIPEA (1.5 eq) in dry DMF (6 - 8 mL/eq) was stirred at 20C for 30 min. Then the above mixture was added to Compound 129D2 (1 eq) and shaken at 20 C for 1.5 hrs. After LCMS showed the reaction was completed, the mixture was filtered and the residue was washed with DMF (3 x 10 mL/mmol), DCM (3 x 10 mL/mmol), THF (3 x 10 mL/mmol) and petroleum ether (3 x 10 mL/mmol) to give Compound 129E1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; In N,N-dimethyl-formamide; toluene; at 20℃; | General procedure: was prepared by stirring amixture of 1a (1.16 g, 5 mmol),SOCl2 (0.59 g, 5 mmol), and several drops of DMF in toluene (30 mL) at ambient temperaturefor 5 hr. The solvent was removed under vacuum. A brown liquid (2a) was obtainedand used to next step without further purifying. | |
With thionyl chloride; In N,N-dimethyl-formamide; toluene; at 20℃; for 5h; | General procedure: 2a was prepared by heating and stirring a mixture of 4-ethyl(4-trans-cyclohexyl)benzoicacid(1a) (1.16 g, 5 mmol) and SOCl2 (0.60 g, 5 mmol) and several drops of DMF in toluene (25 mL) at ambient temperature for 5 hr. The solvent was then removed under vaccum condition. A brown liquid (2a) was obtained and used to next step without further purifying. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.6% | The coupling of an acid chloride to an amine is is described for this example.A mixture of <strong>[59662-46-3]4-(4-butylphenyl)benzoic acid</strong> (200 mg, 0.79 mmol) in thionyl chloride (5.0 mL)was stirred at 60 C for 16 h. The solution was concentrated and dissolved in dichloromethane(2 mL). To the solution of Compound 119-B (500 mg, 0.73 mmol) and triethylamine (74 mg,0.73 mmol) in dichloromethane (15 mL) was added the above solution of 4-(4-butylphenyl)benzoyl chloride in dichloromethane. The reaction mixture was stirred at 25 C for3 h. The reaction was concentrated to dryness and the residue was purified by flash columnchromatography (eluted with 5% dichloromethane in methanol). The desired fractions were concentrated to afford Compound 119-C (650 mg, 96.6% yield) as a white solid. LCMS (5- 95AB/1.5 mm): tR = 0.95 1 mi [M + Hj 921.4. Alternatively, this coupling reaction can be performed using 4?-butyl-[1,1?-biphenylj-4-carboxylic acid using General Method HATUconditions in Example 4. | |
96.6% | The coupling of an acid chloride to an amine is General Method Acid Chlorideand is described for this example. A mixture of <strong>[59662-46-3]4-(4-butylphenyl)benzoic acid</strong> (200 mg, 0.79mmol) in thionyl chloride (5.0 mL) was stirred at 60 C for 16 h. The solution was concentrated and dissolved in dichloromethane (2 mL). To the solution of Compound 331-B (500 mg, 0.73 mmol) and triethylamine (74 mg, 0.73 mmol) in dichloromethane (15 mL) was added the above solution of 4-(4-butylphenyl)benzoyl chloride in dichloromethane. The reaction mixture wasstirred at 25 C for 3 h. LCMS showed that all of start material was consumed completely. TLC (10% dichloromethane in methanol, Rf = 0.4). The reaction was concentrated to dryness and the residue was purified by flash column chromatography (eluted with 5% dichloromethane in methanol). The desired fractions were concentrated to afford Compound 331-C (650 mg, 0.71 mmol, 96.6% yield) as a white solid. LCMS (5-95AB/1.5 mm): tR = 0.95 1 mi [M + Hj 921.4.Alternatively, this coupling reaction can be performed using 4?-butyl-[1,1?-biphenylj-4- carboxylic acid using General Method HATU conditions in Example 4. |
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