Structure of 127049-87-0
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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. : | 127049-87-0 |
Formula : | C7H5BrCl2 |
M.W : | 239.93 |
SMILES Code : | CC1=C(Cl)C(Br)=CC=C1Cl |
MDL No. : | MFCD09878179 |
Boiling Point : | No data available |
InChI Key : | DGAYFCFQKDUHQN-UHFFFAOYSA-N |
Pubchem ID : | 14801175 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 49.13 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.56 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.14 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.06 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.51 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.24 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.9 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.38 |
Solubility | 0.01 mg/ml ; 0.0000417 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.85 |
Solubility | 0.0341 mg/ml ; 0.000142 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.88 |
Solubility | 0.0032 mg/ml ; 0.0000133 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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) |
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 |
-4.82 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 |
0.55 |
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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.71 |
* 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 |
---|---|---|
99.5% | With bromine; iodine; In tetrachloromethane; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; | EXAMPLE 1-1 Preparation of 2,4-dichloro-3-methylbromobenzene To a solution of 48.8 g (0.3 mol) of 2,6-dichlorotoluene in 60 ml of carbon tetrachloride, 0.7 g of iron powder and 0.1 g of iodine were added. Then, 52.8 g (0.33 mol) of bromine was dropwise added thereto at room temperature while maintaining the reaction temperature at a level of from 22 to 25 C. After completion of the dropwise addition, the reaction was continued at the same temperature until generation of hydrogen bromide ceased. After the reaction, the reaction solution was added to 300 ml of ice water and extracted with 300 ml of 1,2-dichloroethane. The organic layer was separated and washed sequentially with water, a saturated sodium hydrogen sulfite aqueous solution, water and a saturated sodium chloride aqueous solution. Then, the solvent was distilled off under reduced pressure to obtain 71.9 g (yield: 99.5%) of desired 2,4-dichloro-3-methylbromobenzene. Melting point: 32-33 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 6.0h;Heating / reflux; | Treat a mixture of <strong>[127049-87-0]1-bromo-2,4-dichloro-3-methyl-benzene</strong> (76.01 g, 0.316 mol) and N-bromosuccinimide (59.2 g, 0.332 mol) in CCl4 (500 mL) with benzoyl peroxide (0.77 g, 3.18 mmol) and is heat to reflux for 6 hours under N2. Cool the reaction mixture to 0 C. and filter using hexanes to rinse the solids. Extract the filtrate with water and saturated NaHCO3. Dry the organic layer (Na2SO4) and remove the solvent in vacuo to afford 97.89 g (97%) of the titled product. Rf=0.34 (100% hexanes). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With bromine; iodine; iron; In tetrachloromethane; at 20.0℃; for 3.33333h; | Treat a mixture of 2,6-dichlorotoluene (50.0 g, 0.31 mol), iodine (0.10 g, 0.39 mmol), and 325 mesh iron powder (0.70 g, 12.5 mmol) in CCl4 (60 mL) dropwise with bromine (52.8 g, 0.33 mol) over 20 minutes and is stir for 3 hours at room temperature. Pour the mixture into ice water and extract with 1,2-dichloroethane. Wash the organic layer with saturated sodium bisulfite and dry using Na2SO4. Remove the solvent in vacuo to afford 76.01 g (100%) 1-bromo-2,4-dichloro-3-methyl-benzene. |
With bromine; iodine; iron; In tetrachloromethane; at 20.0℃; for 48.0h; | To a mixed solution of compound 39-a-1 (5 g, 31.06 mmol), iron powder (87 mg, 1.55 mmol) and iodine (39mg, 0.15 mmol) in carbon tetrachloride was added dropwise bromine (5.22 g, 32.61 mmol) at room temperature. Afterthe addition was complete, the reaction solution was stirred at room temperature for two days. The reaction solutionwas quenched with sodium bisulfite solution, extracted with dichloromethane (2*50 ml), and the organic phase waswashed with saturated brine (30 ml), concentrated and dried to give compound 39-a (4.77 g) as a colorless oil directlyused in the next reaction, purity 76%, yield 64%, MS m/z(ESI):N/A. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 90.0℃; for 5.0h; | To a stirred solution of <strong>[127049-87-0]1-bromo-2,4-dichloro-3-methylbenzene</strong> (500 mg, 2.09 mmol) and 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (637 mg, 2.51 mmol) in 1.4- dioxane was added potassium acetate (304 mg, 3.10 mmol), and the mixture was degassed for 10 min. [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2; 152 mg, 0.2 mmol) was added, and the mixture was degassed for 10 min. The mixture was heated at 90 C for 5 h, was cooled and was diluted with EtOAc. The organic layer was washed with water and brine, dried over Na2S04, and concentrated. Purification by MPLC with 5% EtOAc- Hexane as eluent afforded the title compound as a colorless liquid (430 mg): *H NMR (300 MHz, CDCl3) delta 7.41 (dd, / = 2.07, 8.10 Hz, 1H), 7.26 - 7.23 (m, 1H), 2.47 (s, 3H), 1.37 (s, 12H). Note: The title compound obtained was impure (containing diborane) and used in next step without further purification. |
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