Structure of 93224-85-2
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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. : | 93224-85-2 |
Formula : | C7H4BrClO2 |
M.W : | 235.46 |
SMILES Code : | O=C(O)C1=C(Cl)C=CC=C1Br |
MDL No. : | MFCD00672929 |
Boiling Point : | No data available |
InChI Key : | URGXUQODOUMRFP-UHFFFAOYSA-N |
Pubchem ID : | 33125 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 46.11 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.57 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.65 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.8 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.94 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.54 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.3 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.68 |
Solubility | 0.495 mg/ml ; 0.0021 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.05 |
Solubility | 2.11 mg/ml ; 0.00898 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.25 |
Solubility | 0.134 mg/ml ; 0.000568 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 |
-6.56 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 |
0.56 |
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) |
1.48 |
* 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 |
---|---|---|
In methanol; | To a solution of 2-bromo-6-chlorobenzoic acid (17.7 g, 75.2 mmol) in methanol (200 mL) at 0 C. was added (trimethylsilyl)diazomethane (2M in hexanes, 100 mL, 0.200 mol). The solution was stirred at 0 C. for 1.5 hours, then warmed to room temperature and washed with aqueous sodium bicarbonate and brine, dried over Na2SO4, filtered and concentrated. The residue was subjected to silica gel chromatography eluted with 0-5% ethyl acetate in hexanes to provide methyl 2-bromo-6-chlorobenzoate as a pale yellow oil that gave proton NMR spectra consistent with theory. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | LiOH.H20 (180 mg, 4.24 mmol) was added to a solution of 2-bromo-6-chlorobenzoic acid (i-la) (1.0 g, 4.24 mmol) in THF (30 ml). The mixture was stirred at 25 C for lh. Then the Me2S04 (1.1 g, 8.48 mmol) was added to the reaction mixture. The mixture was warmed to 85 C and stirred at 85 C for 21 h. After cooled, H3.H20 was added dropwise to the mixture until pH=7-8. The solution was poured into water and THF was evaporated. The water layer was extracted with EA (60 ml). The organic layer was dried over Na2S04 and concentrated to obtain 800 mg (75%) of the title compound. LCMS (ESI): calc'd for C8H6BrC102 [M+H]+: 251, found: 251. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.4% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3.66667h; | To a solution 2-bromo-6-chlorobenzoic acid (9.5 g, 0.041 mol) and potassium carbonate (8.6 g, 0.061 mol) in N,N-dimethylformamide (50 mL) was added methyl iodide (11.2 g, 0.081 mol) dropwise over a 10 minute period. The reaction mixture was stirred at RT for 3.5 hours and was subsequently diluted with water (500 mL). The aqueous phase was back-extracted with EtOAc (3*300 mL). The organic layers were combined, washed with 1M HCl aq (100 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the title compound (10.0 g, 99.4%). 1H NMR (400 MHz, CDCl3) delta ppm 7.413 (d, J=8 Hz, 1H), 7.29 (d, J=8 Hz, 1H), 7.137 (t, J=8 Hz, 1H), 3.9 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | LiOH.H20 (180 mg,4.24 mmol) was added to a solution of 2-bromo-6-chlorobenzoic acid (i-la) (1.0 g, 4.24mmol) in THF (30 ml). The mixture was stirred at 25 C for lh. Then the Me2SO4 (1.1 g, 8.48mmol) was added to the reaction mixture. The mixture was warmed to 85 C and stirred at 85C for 21 h. After cooling, NH3.H20 was added dropwise to the mixture until pH=7-8. Thesolution was poured into water and THF was evaporated. The water layer was extracted withEA (60 ml). The organic layer was dried over Na2SO4 and concentrated to obtain 800 mg(75%) of the title compound. LCMS (ESI): calc?d for C8H6BrC1O2 [M+H]: 251, found: 251. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With glycerol-based sulfonic acid functionalized carbon catalyst; for 6h;Reflux; Green chemistry; | General procedure: To a stirred solution of substituted aryl carboxylic acid 1 (0.15 mol) in methanol (0.75 mol) glycerol-based solid acid catalyst (28 wt% of aryl carboxylic acid) was added and heated to reflux for 6 h. After completion of the reaction as indicated by TLC, the reaction mixture was cooled to room temperature. The catalyst was separated by filtration and was washed with methanol for recycle. Methanol was then distilled off under reduced pressure to get the pure methyl ester 2. |
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