Structure of 52787-14-1
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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. : | 52787-14-1 |
Formula : | C11H12O4 |
M.W : | 208.21 |
SMILES Code : | O=C(OC)C1=CC=C(CC(OC)=O)C=C1 |
MDL No. : | MFCD07779210 |
Boiling Point : | No data available |
InChI Key : | QAQYBHOZQQRJBA-UHFFFAOYSA-N |
Pubchem ID : | 10536335 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.27 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 53.59 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.6 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.48 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.12 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.19 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.84 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.99 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.92 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.43 |
Solubility | 0.769 mg/ml ; 0.00369 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.86 |
Solubility | 0.29 mg/ml ; 0.00139 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.96 |
Solubility | 0.228 mg/ml ; 0.00109 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) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.06 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 |
0.0 |
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) |
1.62 |
* 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 |
---|---|---|
94.4% | With lithium hydroxide monohydrate; water; In tetrahydrofuran; ethanol; at 25℃; for 10h; | 2- (4- (methoxycarbonyl) phenyl) acetic acid (58,24.04 dirty 1) to the reaction flask, 31111 water, 31111 5ml tetrahydrofuran and a mixed solvent of ethanol raw materials were dissolved. Was then added Eta0Eta-Eta20 (1.068,25.24pipiomicron1) alpha25 C was stirred for 10 hours the reaction is substantially complete. The solution was spin-off in tetrahydrofuran and ethanol, followed by addition of 26ml of dilute hydrochloric acid (lmmol / L), and a white precipitate formed, suction, infrared drying to give a white solid 4.4g, 94.4% yield |
83% | With potassium carbonate; In methanol; water; at 20℃; for 4h; | A solution of methyl 4- (2-methoxy-2-oxoethyl) benzoate 26, (800 mg, 3.85 ramol) and K2CO3 (929 mg, 5.67 mmol) in water/methanol mixture (20 mL, 1:1) was stirred at room temperature 4 hrs. After concentrating the reaction mixture to 5 mL diluted with water (20 mL) . Then the aqueous layer was washed with dichloromethane (20 mL chi 2), and acidified to pH~3 with 12M HC1. The aqueous solution was extracted with ethyl acetate (20 mL * 2) . Organics was combined, dried over NaaSOi and evaporated in vacuo to give titled compound 27. (620 mg, 83%). NMR (CHCI3, 400 MHz): delta 7.90 (d, J=8.1 Hz, 1H), 7.42 (d, J=8.1, 1H) , 3.85 (s, 3H) , 3.68 (s, 2H) ; [M+H]+ = 195.4 (APCI+) . |
80% | With hydrogenchloride; In methanol; at 20 - 50℃; for 28h; | Step 2: 2-(4-(Methoxycarbonyl)phenyl)acetic Acid A stirred solution of methyl 4-(cyanomethyl)benzoate (22.0 g, 0.125 mol) in methanol (550 mL) was bubbled through with hydrogen chloride gas for 8 h under reflux conditions. The reaction mixture was cooled to 20 C., stirred for an additional 24 h and filtered. The filtrate was evaporated under reduced pressure. The resultant residue was dissolved in diethyl ether, washed sequentially with water and saturated aqueous sodium hydrogen carbonate, dried over sodium sulfate and evaporated to afford the methyl ester as a solid residue. 1H NMR (400 MHz, CDCl3): 8.00 (d, J=8 Hz, 2H); 7.35 (d, J=8.4 Hz, 2H); 3.91 (s 3H); 3.70 (s, 3H); 3.68 (s, 2H). GCMS: 209 (M+H). The methyl ester (8.21 g, 0.039 mmol) was dissolved in methanol, treated with sodium hydroxide (1.58 g, 0.039 mol), heated to 50 C., stirred for 4 h, cooled to room temperature, stirred for an additional 24 h and concentrated in vacuo. The resultant residue was partitioned between diethyl ether and water. The aqueous layer was acidified with concentrated HCl. The resultant precipitate was removed by filtration and dried overnight, under vacuum, to afford 2-(4-(methoxycarbonyl)phenyl)-acetic acid (80%) as an off-white solid. 1H NMR (400 MHz, DSMO-d6): 7.90 (d, J=8 Hz, 2H); 7.422 (d, J=8 Hz, 2H); 3.85 (s 3H) 3.68 (s, 2H). [M+H] 195 |
64.4% | With potassium carbonate; In methanol; water; at 20℃; for 1.5h; | Methyl 4-(2-methoxy-2-oxoethyl)benzoate (100 mg, 0.48 mmol), methanol (1.5 mL), water (1.5 mL) and anhydrous potassium carbonate (116 mg, 0.72 mmol) were added in a 10 mL single-neck flask, and the mixture was stirred at room temperature for 1.5 hours. After the materials had all reacted when being determined by TLC, solvent was removed in vacuo, and the residue was redissolved in ethyl acetate (1 mL) and separated by preparative thin layer chromatography (petroleum ether: ethyl acetate = 1:1) to give a product (white solid, 60 mg), with a yield of 64.4%. 1H NMR (400 MHz, CDCl3) delta 8.00 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 3.91 (s, 3H), 3.70 (s, 2H). |
With lithium hydroxide; In tetrahydrofuran; methanol; water; | iv. 4-Methoxycarbonylphenylacetic acid. To a solution of methyl 4-methoxycarbonylphenylacetate (3.15 g) dissolved in tetrahydrofuran (100 mL), methanol (25 mL) and water (25 mL) at 0 C. was added lithium hydroxide (0.7 g) and the solution was allowed to stir for 2 h. The solution was acidified to pH 2.5 and the product extracted into ethyl acetate. The organic layer was dried (MgSO4) and evaporated to give an oil which was crystallized from hexane to give the mono-acid; TLC: Rf =0.65, methanol:dichloromethane (20:80); MS: m/z=195(M+1). | |
A stirred solution of methyl 4-(cyanomethyl)benzoate (22.0 g, 0.125 mol) in methanol (550 mL) was bubbled through with hydrogen chloride gas for 8 h under reflux conditions. The reaction mixture was cooled to 20 C., stirred for an additional 24 h and filtered. The filtrate was evaporated under reduced pressure. The resultant residue was dissolved in diethyl ether, washed sequentially with water and saturated aqueous sodium hydrogen carbonate, dried over sodium sulfate and evaporated to afford the methyl ester as a solid residue. 1H NMR (400 MHz, CDCl3): 8.00 (d, J=8 Hz, 2H); 7.35 (d, J=8.4 Hz, 2H); 3.91 (s 3H); 3.70 (s, 3H); 3.68 (s, 2H). GCMS: 209 (M+H). The methyl ester (8.21 g, 0.039 mmol) was dissolved in methanol, treated with sodium hydroxide (1.58 g, 0.039 mol), heated to 50 C., stirred for 4 h, cooled to room temperature, stirred for an additional 24 h and concentrated in vacuo. The resultant residue was partitioned between diethyl ether and water. The aqueous layer was acidified with concentrated HCl. The resultant precipitate was removed by filtration and dried overnight, under vacuum, to afford 2-(4-(methoxycarbonyl)phenyl)-acetic acid (80%) as an off-white solid. 1H NMR (400 MHz, DSMO-d6): 7.90 (d, J=8 Hz, 2H); 7.422 (d, J=8 Hz, 2H); 3.85 (s 3H) 3.68 (s, 2H). [M+H] 195 |
A158946 [22744-12-3]
2-(4-(Methoxycarbonyl)phenyl)acetic acid
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A243218 [52787-19-6]
2-(3-(Methoxycarbonyl)phenyl)acetic acid
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A144199 [N/A]
2-(2-(Methoxycarbonyl)phenyl)acetic acid-Deleted-NAME
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A158946 [22744-12-3]
2-(4-(Methoxycarbonyl)phenyl)acetic acid
Similarity: 1.00
A243218 [52787-19-6]
2-(3-(Methoxycarbonyl)phenyl)acetic acid
Similarity: 1.00
A144199 [N/A]
2-(2-(Methoxycarbonyl)phenyl)acetic acid-Deleted-NAME
Similarity: 0.98