Structure of 65340-70-7
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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. : | 65340-70-7 |
Formula : | C9H5BrClN |
M.W : | 242.50 |
SMILES Code : | C1=C(Br)C=CC2=C1C(=CC=N2)Cl |
MDL No. : | MFCD00511001 |
InChI Key : | KJILYZMXTLCPDQ-UHFFFAOYSA-N |
Pubchem ID : | 5139537 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P264-P271-P280-P305+P351+P338-P302+P352-P304+P340-P312-P362+P364-P403+P233-P501 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 54.45 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.37 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.51 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.65 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.12 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.76 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.28 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.17 |
Solubility | 0.0163 mg/ml ; 0.0000674 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.46 |
Solubility | 0.0833 mg/ml ; 0.000343 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.17 |
Solubility | 0.00162 mg/ml ; 0.00000668 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) |
Yes |
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 |
-5.29 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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.44 |
* 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 |
---|---|---|
With triethylamine; In DMF (N,N-dimethyl-formamide); at 130℃; for 8h; | Production Example 82 1-(6-Bromo-4-quinolyl)-4-piperidyl methyl ether A mixture of 500 mg 6-bromo-4-chloroquinoline, 330 mg <strong>[4045-25-4]4-methoxypiperidine monohydrochloride</strong>, 0.57 ML triethylamine and 10 ML N,N-dimethylformamide was stirred at 130C for 8 hours.. Ethyl acetate and water were added to the reaction solution, and the organic layer was separated.. The organic layer was washed with water and brine and dried over sodium sulfate, and the solvent was evaporated.. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give 516mg of the title compound as a pale yellow oil.1H-NMR (CDCl3) delta: 1.85-1.98(m, 2H), 2.08-2.20(m, 2H), 2.97-3.08(m, 2H), 3.38-3.55(m, 6H), 6.85(d, J=5.0Hz, 1H), 7.70(d, J=8.6Hz, 1H), 7.90(d, J=8.6Hz, 1H), 8.12(s, 1H), 8.69(d, J=5.0Hz, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.8% | In methanol; at 20 - 120℃; for 15h; | To a solution of 6-bromo-4-chloro-quinoline (12.12 g, 50 mmol) in methanol (200 mL) was added sodium methoxide (13.50 g, 250 mmol) at room temperature. Then, the reaction mixture was heated to 120 C. for 15 h in a sealed reaction flask. After cooling to room temperature, the methanol was removed under the vacuum and the residue was diluted with water. Then, the solids were collected by filtration and washed with water. After drying in air, 10.8 g (90.8% yield) of 6-bromo-4-methoxy-quinoline was isolated as a white solid which can be crystallized from acetonitrile: EI-HRMS m/e calcd for C10H8BrNO (M+) 236.9789, found 236.9784. |
36% | In methanol; at 120℃; for 1h;Microwave irradiation; | 300 mg (1.24 mmol) of 6-bromo-4-chloroquinoline [Lin et al., J. Med. Chem. 1978, 21, 268] was taken up in 4 ml methanol and 1.15 ml (6.19 mmol) methanolic sodium methylate solution (30 wt.%) was added. Then it was reacted in a single mode microwave for 1 h at 1200C. The solvent was removed in a rotary evaporator and the residue was partitioned between water and ethyl acetate. The aqueous phase was extracted with ethyl acetate and the combined organic phases were dried over magnesium sulfate. The solvent was removed by distillation at reduced pressure. In this way we obtained 150 mg (36% of theor.) of the target compound.LC-MS (method 2): R, = 1.24 min; MS (EIpos): m/z = 238 [M]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 100℃; for 1h; | A 5 mL microwave vial was charged with 4-chloro-6-bromoquinoline (0.15 g, 0.62 mmol) and a 25 wt % solution of sodium methoxide in methanol (2.0 mL, 8.8 mmol). The vial was sealed and heated to 100C for 60 minutes under microwave irradiation (Biotage, Initiator). After cooling, the solvent was removed in vacuo, the residue washed with water, filtered and dried via .yophilization to obtain 6-bromo-4-methoxyquinoline.LRMS (ESI) calc'd for C10H9BrNO [M+H]+: 238, Found: 238. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In ethanol; for 18.0h;Reflux; Inert atmosphere; | General procedure: 6-Bromo-4-chloroquinoline (1.0 equiv.) and 3,4,5-trimethoxyaniline (1.1 equiv.) were suspended in ethanol (10 mL) and refluxed for 18 h. The crude mixture was purified by flash chromatography using EtOAc:hexane followed by 1-5% methanol in EtOAc, solvent was removed under reduced pressure to afford the desired product (1, 8-11, 13-31, and 33-43). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In ethanol; for 18h;Reflux; Inert atmosphere; | General procedure: 6-Bromo-4-chloroquinoline (1.0 equiv.) and 3,4,5-trimethoxyaniline (1.1 equiv.) were suspended in ethanol (10 mL) and refluxed for 18 h. The crude mixture was purified by flash chromatography using EtOAc:hexane followed by 1-5% methanol in EtOAc, solvent was removed under reduced pressure to afford the desired product (1, 8-11, 13-31, and 33-43). |
In ethanol; at 85℃; for 18h; | General procedure: 4-chloroquin(az)oline derivative (1.0eq.), aniline derivative (1.1 eq.), were suspended in ethanol (10 mL) and refluxed for 18 h. The crudemixture was purified by flash chromatography using EtOAc:hexane followed by 1-5 % methanol in EtOAc; After solvent removal under reduced pressure, the product was obtained as a free following solid or recrystallized from ethanol/water. Compounds 4-31 were synthesized as previous described[38, 48], 32-51 were synthesized as previous described [42]. Representative supporting information provided. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | In ethanol; for 18.0h;Reflux; Inert atmosphere; | General procedure: 6-Bromo-4-chloroquinoline (1.0 equiv.) and 3,4,5-trimethoxyaniline (1.1 equiv.) were suspended in ethanol (10 mL) and refluxed for 18 h. The crude mixture was purified by flash chromatography using EtOAc:hexane followed by 1-5% methanol in EtOAc, solvent was removed under reduced pressure to afford the desired product (1, 8-11, 13-31, and 33-43). |
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