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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
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Structure of 4659-45-4
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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.
4.5
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Search for reports by entering the product batch number.
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CAS No. : | 4659-45-4 |
Formula : | C7H3Cl3O |
M.W : | 209.46 |
SMILES Code : | O=C(Cl)C1=C(Cl)C=CC=C1Cl |
MDL No. : | MFCD00000662 |
InChI Key : | JBLIDPPHFGWTKU-UHFFFAOYSA-N |
Pubchem ID : | 78392 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P264-P280-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P363-P405-P501 |
Class: | 8 |
UN#: | 3265 |
Packing Group: | Ⅱ |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 46.65 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.03 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.21 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.37 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.2 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.62 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.09 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.5 |
Solubility | 0.0665 mg/ml ; 0.000317 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.24 |
Solubility | 0.12 mg/ml ; 0.000575 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.2 |
Solubility | 0.0132 mg/ml ; 0.0000631 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) |
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 |
-5.3 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 |
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) |
1.33 |
* 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 |
---|---|---|
Fmoc-Phe(4-nitro)-OH (2.5g), 2,6-dichlorobenzoyl chloride (0.745mL) and pyridine (1.5mL) in a solution of NMP (25mL) were added to Wang resin (0.76mmol/g, 2.3g) and stirred at room temperature for 16 hours. After removing the excess solvent, the resin was washed with DMF three times, dichloromethane three times and NMP twice. In order to conduct capping of an unreacted hydroxyl group on the resin, the resin was treated with acetic anhydride (20mL), pyridine (20mL) and NMP (20mL) for 2 hours. After removing the excess solvent, the resin was washed with DMF three times and dichloromethane three times, and dried under reduced pressure.Process 2 Removal of Fmoc group A DMF solution of 20% piperidine (25mL) was added to the resin obtained in Process 1 and reacted for 15 minutes. After removing the solvent, the resin was washed with DMF and dichloromethane three times each, and dried under reduced pressure.Process 3 Acylation reaction 2,6-dichlorobenzoyl chloride (1.1mL), 2,6-lutidine (1.6mL) and NMP (26mL) were added to 2.0g of the resin obtained in Process 2 and reacted for 6 hours. After removing the excess solvent, the resin was washed with DMF and dichloromethane three times each, and dried under reduced pressure.Process 4 Reduction of nitro group NMP (30mL) · EtOH (1.5mL) solution of SnCl2· 2H2O (15.0g) was added to 1.5g of the resin obtained in Process 3 and reacted for 16 hours. After removing the reaction solvent, the resin was washed with DMF and dichloromethane three times each.Process 5 Construction of quinazoline-2,4-dione ring 2g of the resin obtained in Process 4 was reacted in NMP solution (32mL) of methyl 2-isocyanatebenzoate (1.92g) for 16 hours. After removing the reaction solvent, the resin was washed with DMF and dichloromethane three times each. DMF solution of 20% piperidine was added to the resin for 1 hour. After removing the reaction solvent, the resin was washed with DMF and dichloromethane three times each and dried under reduced pressure.Process 6 Alkylation Methyl iodide (0.75mmol), 18-crown-6 (30mg), NMP (1mL) and K2CO3 (35mg) were added to 20mg of the resin obtained in Process 5 and reacted for 3 days. After removing the reaction solvent, the resin was washed with DMF, water, DMF and dichloromethane three times each and dried under reduced pressure.Process 7 Cleavage from resin The resin obtained in Process 6 was treated with trifluoroacetic acid containing 5% of water for 1 hour. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified with high-pressure liquid chromatography (water/acetonitrile) to obtain 8mg of the intended compound. MS(ESI MH+) : 512 CHNO : C25H19Cl2N3O5 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 0 - 20℃; for 12.0h; | EXAMPLE 16 [0322] This example describes the synthesis of which was prepared according to the procedure below. [0323] To a solution of 0.2 mmol of compound 8.4 (Example 8c or 8e) in 1 mmol of Et3N and 5 mL of dry CH2C12 was added 0.22 mmol of 2,6- dichlorobenzoyl chloride at 0C, the resulting mixture was stirred at room temperature for 12 hours. The solvent was removed and the residue was dried in vacuo. Subsequently, the residue was treated with 0. 8 mmol of LiOH-H20 in 2 mL of THF and 0.5 mL of H20. After stirring at room temperature for 30 minutes, the reaction mixture was added 1.0 mL of 1. ON aq. HC1. The organic solvent was removed, and the residue was diluted with 10 mL of brine. The mixture was extracted with EtOAc and the extract was dried with anhydrous Na2SO4. The solvent was removed and the residue was dried in vacuo to give the desired compound in 65% yield. 1H NMR (400 MHz, CD30D) 6 7.92 (s, 1 H), 7. 82 (d, J=6. 85 Hz, 1 H), 7.71 (d, J=6. 85 Hz, 1 H), 7.56 (t, J=7. 83 Hz, 1 H), 7.34 (m, 3 H), 5. 08 (dd, J=9. 78, 4.89 Hz, 1 H), 3.45 (dd, J=14. 67,4. 89 Hz, 1 H), 3.14 (dd, J=14. 67,9. 78 Hz, 1 H), 3.08 (s, 3 H) ppm; ESI-MS (m/z) : (M+H+) 416.00. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; at 3 - 20℃; for 3.16667h;Inert atmosphere; | 2,6-Dichlorobenzoyl chloride (13.7 mL,95.6 mmol) was added dropwise, over 10 minutes, to a solution of <strong>[159783-22-9]3,5-difluoropyridin-4-ylamine</strong> (10.37 g,79.7 mmol) in pyridine (160 mL) at a temperature of between 3 and 5 C, under argon. The reaction mixture was allowed to warm to room temperature over 1 hour and then stirred at room temperature for 2 hours. The volatiles were removed under reduced pressure and the resultant residue was treated with HC1 (IN, 120 mL). The resultant suspension was stirred at room temperature for 45 minutes and the precipitate was collected by filtration, washing with water. A mixture of 2,6-dichloro-N-(3,5-difluoropyridin-4-yl)-benzamide and of 2,6- dichloro-N-(2,6-dichlorobenzoyl)-N-(3,5-difluoropyridin-4-yl)-benzamide (22.0 g) was obtained.A suspension of this mixture (22.0 g) in IN NaOH (200 mL) and MeOH (200 mL) was heated at 65 C for 7 hours then slowly cooled to room temperature. The pH of the mixture was adjusted to 4-5 by dropwise addition of 12N HC1, controlling the exotherm by the use of an ice-bath. The residue was left standing at room temperature for 18 hours and then the resultant solid was collected by filtration, washing with water, to afford the title compound as an off-white solid (14.65 g, 61% yield over two steps). LCMS (Method D): RT = 2.93 min, m/z: 303 [M+H+]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; triethylamine; In tetrahydrofuran; at 90℃; for 4h; | To a solution of <strong>[271-73-8]1H-<strong>[271-73-8]pyrazolo[3,4-b]pyridine</strong></strong> (500 mg, 4.20 mmol) in THF (8 mL) was added 2,6-dichlorobenzoyl chloride (879 mg, 4.20 mmol), TEA (1.755 mL, 12.59 mmol) and DMAP (256 mg, 2.099 mmol). The reaction was stirred at 90° C. for 4 hours. LCMS show no starting material and the desired product formed. The reaction mixture was concentrated and purified by silica gel column chromatography (SiO2, EtOAc/PE=0percent to 50percent) to give (2,6-dichlorophenyl)(1H-pyrazolo[3,4-b]pyridin-1-yl)methanone. MS: 292 (M+1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 3h;Cooling with ice; | Comparative Example 2 2,6-dichloro-N-[(2,3-dihydro-1,4-benzodioxin-6-yl)methyl]benzamide To a mixture of 2,3-dihydro-1,4-benzodioxin-6-yl)methylamine (50 mg, 0.30 mmol) and dichloromethane (1 mL) were added N,N-diisopropylethylamine (0.11 mL, 0.61 mmol) and 2,6-dichlorobenzoyl chloride (0.043 mL, 0.30 mmol) under ice cooling and the resultant was stirred at room temperature for 3 hours. The reaction mixture was purified by column chromatography on silica gel (heptane:ethyl acetate=2:1) to give the title compound (94 mg, 92% yield), 1H-NMR Spectrum (CDCl3) delta (ppm): 4.24 (s, 4 H), 4.57 (d, J=5.47 Hz, 2 H), 5.94 (br. s, 1 H), 6.81-6.92 (m, 3 H), 7.21 -7.33 (m, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With aluminium trichloride; at 40℃; | Hereinafter there are listed examples of ketones obtainalbe or obtained by the process of the invention: hexanone-3 decanone-4 ... o-chloropropiophenone m-chloroacetophenone 3-chloro-5-methylpropiophenone 2,6-dichloroacetophenone m-bromopropiophenone p-bromoacetophenone p-bromopropiophenone ... |
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