Structure of 1070879-27-4
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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.
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CAS No. : | 1070879-27-4 |
Formula : | C10H8BrNO |
M.W : | 238.08 |
SMILES Code : | COC1=CC=C2C(Br)=CC=NC2=C1 |
MDL No. : | MFCD08063187 |
InChI Key : | HSLGTRSMCWHZQH-UHFFFAOYSA-N |
Pubchem ID : | 21568292 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.1 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 55.94 |
TPSA ? Topological Polar Surface Area: Calculated from |
22.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.33 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.98 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.01 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.19 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.1 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.72 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.7 |
Solubility | 0.0479 mg/ml ; 0.000201 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.11 |
Solubility | 0.186 mg/ml ; 0.00078 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.69 |
Solubility | 0.00489 mg/ml ; 0.0000206 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 |
-5.64 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 |
0.55 |
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) |
1.66 |
* 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 triphenylphosphine; lithium chloride;bis-triphenylphosphine-palladium(II) chloride; In DMF (N,N-dimethyl-formamide); at 20 - 120℃; for 16h; | 4 g of triphenylphosphine, 5.3 g of lithium chloride, 14 ml of tetramethyltin and 2.1 g of bis(triphenylphosphine)palladium(II) chloride are added to a solution of 6 g of <strong>[1070879-27-4]4-bromo-7-methoxyquinoline</strong> in 100 ml of DMF, under an inert atmosphere of argon at a temperature in the region of 20° C. The reaction medium is heated at a temperature in the region of 120° C. for 16 hours. After cooling, the insoluble material is filtered off. The filtrate is concentrated under reduced pressure. The residue obtained is taken up in 300 ml of EtOAc and 300 ml of water. After separation of the phases by settling, the organic phase is dried over magnesium sulfate, filtered and then concentrated under reduced pressure. The oil obtained is taken up in 300 ml of EtOAc and 300 ml of water and then acidified with hydrochloric acid to pH 1. The aqueous phase is basified with sodium hydroxide to pH 10 and then extracted with 300 ml of EtOAc. After separation of the phases by settling, the organic phase is dried over magnesium sulfate, filtered and then concentrated under reduced pressure to give 2.7 g of 4-methyl-7-methoxyquinoline, the characteristics of which product are as follows: 1H NMR spectrum (300 z, (CD3)2SO d6, delta in ppm): 2.65 (s: 3H); 3.94 (s: 3H); 7.23 (broad d, J=4.5 Hz: 1H); 7.28 (dd, J=9 and 3 Hz: 1H); 7.40 (d, J=3 Hz: 1H); 8.01 (d, J=9 Hz: 1H); 8.58 (d, J=4.5 Hz: 1H). Mass IE m/z=173 M+. base peak m/z=158 (M-CH3)+ m/z=143 (M-CH2O)+. m/z=130 (m/z=158-CO)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With phosphorus(V) oxybromide; at 110℃; | General procedure: According to Scheme C,7-Methoxyquinolin-4-ol (1 eq) and POBr3 (10.4 eq.) Were placed in a round bottom flask,And the mixture was stirred for 3 hours. After completion of the reaction, the reaction solution was slowly added to the ice water and basified to pH 8 or more with ammonia water.The organic layer was extracted three times with ethyl acetate from the mixture of water and solution, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained mixture was subjected to column chromatography to give 4-bromo-7-methoxyquinoline. (1 eq.), 2-benzyl-4,4,5,5-tetramethyl-l, 3,2-dioxaborolane (1.2 eq.), Potassium carbonate (3 eq.), Tetrakis Phosphine) palladium (0) (0.05 eq.) Was stirred at 100 for 6 h under a solution of 1,4-dioxane and water in a ratio of 4: 1. After cooling to room temperature, the mixture was extracted three times with ethyl acetate, dried over anhydrous magnesium sulfate and filtered, and then concentrated under reduced pressure. Subsequently, a 4-benzylquinoline compound was obtained by column chromatography. |
With phosphorus(V) oxybromide; at 110℃; for 3.0h; | 22.74 g of 4-hydroxy-7-methoxyquinoline are added to 200 g of phosphorus oxybromide preheated to a temperature in the region of 110 C. The reaction medium is heated at this same temperature for 3 hours. The reaction medium is poured, while hot, into a mixture of 500 ml of EtOAc and 500 ml of ice-cold water. The medium is neutralized with potassium carbonate to pH 7. After separation of the phases by settling, the organic phase is dried over magnesium sulfate, evaporated under reduced pressure and then purified by column chromatography (SiO2, EtOAc/cyclohexane 50/50 by volume as eluents, Ar), and 14.6 g of the expected product are obtained. [1475] 1H NMR spectrum (300 MHz, (CD3)2SO d6, delta in ppm): 3.97 (s: 3H); 7.43 (dd, J=9 and 3 Hz: 1H); 7.49 (d, J=3 Hz: 1H); 7.79 (d, J=4.5 Hz: 1H); 8.06 (d, J=9 Hz: 1H); 8.67 (d, J=4.5 Hz: 1H). [1476] Mass IE m/z=237 M+. base peak [1477] 4-Hydroxy-7-methoxyquinoline is prepared according to the process described in: J. Am. Chem. Soc., 68, 1268, 1946. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Exemplary of the 4-bromoquinoline compounds are: 4-bromoquinoline; 4-bromo-6-methoxyquinoline; 4-bromo-6-methylquinoline; 4-bromo-7-methoxyquinoline; 4-bromo-6,7-dimethoxyquinoline; 4-bromo-6,7-methylenedioxyquinoline; ... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; | General procedure: According to Scheme C,7-Methoxyquinolin-4-ol (1 eq) and POBr3 (10.4 eq.) Were placed in a round bottom flask,And the mixture was stirred for 3 hours. After completion of the reaction, the reaction solution was slowly added to the ice water and basified to pH 8 or more with ammonia water.The organic layer was extracted three times with ethyl acetate from the mixture of water and solution, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained mixture was subjected to column chromatography to give <strong>[1070879-27-4]4-bromo-7-methoxyquinoline</strong>. (1 eq.), 2-benzyl-4,4,5,5-tetramethyl-1, 3,2-dioxaborolane (1.2 eq.), Potassium carbonate (3 eq.), Tetrakis Phosphine) palladium (0) (0.05 eq.) Was stirred at 100 C for 6 h under a solution of 1,4-dioxane and water in a ratio of 4: 1. After cooling to room temperature, the mixture was extracted three times with ethyl acetate, dried over anhydrous magnesium sulfate and filtered, and then concentrated under reduced pressure. Subsequently, a 4-benzylquinoline compound was obtained by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | (0640) <strong>[1070879-27-4]4-bromo-7-methoxyquinoline</strong> (204 mg, 0.86 mmol) was dissolved in anhydrous THF in -78C, n- butyl lithium was added slowly. The reaction mixture was stirred at -78C for 2h, and then 3-methyl-4-anisaldehyde (257 mg, 1.72 mmol) was added slowly, the mixture was slowly warmed to room temperature and stirred overnight. The mixture was then diluted with water and extracted with ethyl acetate. The organic phase was dried and concentrated. The crude product was purified by flash chromatography (dichloromethane / ethyl acetate 0-10%) to yield product as a yellow solid (243 mg, 91% yield). ESI-MS m/z: 310.1444 [M+H]+; Punty: 99.6%. 1H NMR (400 MHz, chlorofornw/) delta 8.89 (d, J= 4.5 Hz, 1H), 7.77 (d, J = 9.3 Hz, 1H), 7.63 (dd, J = 4.5, 0.9 Hz, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.15- 7.02 (m, 3H), 6.75 (d, J = 9.0 Hz, lH), 6.39 (s, 1H), 3.92 (s, 3H), 3.79 (s, 3H), 2.16 (s, 3H). 13C NMR (101 MHz, CDCI3) delta 160.05, 157.80, 150.33, 148.58, 133.87, 129.80, 126.07, 125.09, 120.63, 119.78, 1 16.29, 110.08, 72.69, 55.64, 55.48, 16.48. |
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