Structure of 166272-81-7
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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. : | 166272-81-7 |
Formula : | C8H7ClO3 |
M.W : | 186.59 |
SMILES Code : | COC(=O)C1=CC(O)=C(Cl)C=C1 |
MDL No. : | MFCD11505968 |
Boiling Point : | No data available |
InChI Key : | JTYWGSFSTNIJTA-UHFFFAOYSA-N |
Pubchem ID : | 11819787 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 44.75 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.04 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.01 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.83 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.91 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.85 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.93 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.5 |
Solubility | 0.588 mg/ml ; 0.00315 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.61 |
Solubility | 0.454 mg/ml ; 0.00243 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.52 |
Solubility | 0.569 mg/ml ; 0.00305 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 |
-6.01 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 |
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) |
1.42 |
* 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 |
---|---|---|
84% | With thionyl chloride; at 70℃; for 2h; | Thionyl chloride (6 g) was added to a solution of <strong>[34113-69-4]4-chloro-3-hydroxybenzoic acid</strong> (4.4 g, 25.50 mmol) in methanol (100 mL) and the reaction was stirred for 2 h at 70C. Then the reaction was concentrated in vacuo. The resulting solution was diluted with n-hexane (50 mL). The solids were collected by filtration, dried in an oven under reduced pressure to afford methyl 4-chloro-3-hydroxybenzoate as a light yellow solid (4 g, 84%). LC/MS (ES, m/z): [M+H]+ 187.0 *H NMR (300 MHz, DMSO) δ 10.69 (s, 1H), 7.55 (d, / = 2.10 Hz, 1H), 7.49 (d, / = 8.40 Hz, 1H), 7.36 - 7.40 (m, 1H), 3.83 - 3.85 (d, / = 8.40 Hz, 3H) |
83% | With thionyl chloride; at 0℃; for 3h;Reflux; | General procedure: To a solution of 2-fluoro-5-hydroxybenzoic acid(1.56 g, 10 mmol) in anhydrous methanol (10 mL), thionly chloride (1.42 mL, 20mmol) was added dropwise at 0 C. The reaction was allowed to warm to rt andreflux for 3 h. The solvent was removed under reduced pressure, water wasadded, and the mixture was extracted with DCM (80 mL). The organic layer was washedwith water, saturated brine, dried over anhydrous sodium sulfate, evaporated togive title compound as a white solid (1.5 g, 88% yield), which was used in thefollowing step without any further purification |
sulfuric acid; for 30h;Heating / reflux; | Example VII This example illustrate the preparation of [4-Methoxy-4-(3-phosphoryloxy-4-chlorophenyl)] spiro [1, 2-dioxetane-3,2'-(5-methoxy(D3)admantane)], disodium salt (56).; The sequence of the reactions in accordance herewith: (a). Synthesis of Methyl 3-hydroxy-4-chlorobenzoate (50), (a starting ester). In a 250mL round bottom flask, 15 parts of 3-hydroxy-4-chlorobenzoicacid (11, commercially available) was dissolved in methanol (150mL) and concentrated sulfuric acid (2mL). The reaction mixture was heated at reflux for 30 hours. TLC on silica gel plates showed formation of the product The solvent was evaporated under reduced pressure and the residue was dissoved in ethyl acetate (150 ml). The organic layer was washed with 5% aqueous sodium bicarbonate solution (100mL) and deionized water (150mL). The organic sovent was dried over anhydrous sodium sulfate and filtered. The solvent was evaporated under reduced pressure and residue purified by chromatography on silica gel column eluting with 25% ethyl acetate-hexanes. Product containing fractions were checked by TLC on silica gel plates & combined. The solvent was evaporated under reduced pressure gave 14.5 parts of the titile compound (50) as off-white solid. The structure was confirmed by 1H NMR. The reaction proceeded as follows : |
With sulfuric acid; for 2h;Reflux; | A 500 mL round bottomed flask was charged with 4-chloro-3-hydroxy-benzoic acid (30 g, 0.175 mmol), 200 mL of MeOH and 10 mL of H2SO4. The resultant mixture was refluxed for 2 hours and then concentrated. Then ethyl acetate and water was added. The organic phase was dried over anhydrous Na2SO4 and then concentrated to give methyl 4-chloro-3-hydroxy-benzoate which used directly in the next step. | |
With sulfuric acid; for 2h;Reflux; | Step 1: Preparation of methyl 4-ehIoro-3-h droxy-ben/oate A 500 ml, round bottomed flask was charged with 4-chloro-3-hydroxy-benzoic acid (30 g, 0. 1 75 mmol), 200 mL of MeOt 1 and 10 mL of H2SO4. The resultant mixture was refluxed for 2 hours and then concentrated. Then ethyl acetate and water was added. The organic phase was dried over anhydrous NajSOa and then concentrated to give methyl 4-chloro-3-hydroxy-benzoate which used directly in the next step. | |
902 mg | With sulfuric acid; at 75℃; for 14h; | To a stirred solution of <strong>[34113-69-4]4-chloro-3-hydroxybenzoic acid</strong> (690 mg, 4.00 mmol) in methanol(8.0 mL) was added sulfuric acid (10 jiL, 0.20 mmol) and the mixture was heated at 75 C for14 h. The mixture was concentrated, residue was cooled to 0 C and neutralized using aqueous sodium bicarbonate solution. The mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water followed by brine and dried over anhydrous sodium sulfate. The solution was filtered, concentrated to yield 902 mg of thedesired product. ‘H NMR (400 MHz, DMSO-d6) ö 3.91 (s, 3H), 5.66 (d, J = 4.4 Hz, 1H),7.39 (d, J = 8.3 Hz, 1H), 7.56 (dd, J = 8.3, 2.0 Hz, 1H), 7.69 (d, J = 2.0 Hz, 1H); ESI-MS (m/z) 187 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol hydrochloride; | 4-Chloro-3-hydroxy-benzoic acid methyl ester 5 g (29 mmol) of 4-Chloro-3-hydroxy-benzoic acid was suspended in 30 ml of saturated methanolic HCl and stirred at room temperature for 16 h. 20 ml of saturated methanolic HCl was added and stirred at room temperature for a further 16 h. The solvent was removed under reduced pressure, and the residue was dried under reduced pressure. Yield 5.3 g. MS (ES+): m/e=187 (M+H)+. |
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