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Structure of 885270-32-6
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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. : | 885270-32-6 |
Formula : | C8H8BrClO |
M.W : | 235.51 |
SMILES Code : | COC1=CC(Cl)=CC(CBr)=C1 |
MDL No. : | MFCD08234654 |
InChI Key : | NOYAZORDAAINEF-UHFFFAOYSA-N |
Pubchem ID : | 53403078 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H314 |
Precautionary Statements: | P501-P260-P270-P264-P280-P303+P361+P353-P301+P330+P331-P363-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P405 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 50.78 |
TPSA ? Topological Polar Surface Area: Calculated from |
9.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.6 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.08 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.09 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.17 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.46 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.08 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.51 |
Solubility | 0.0724 mg/ml ; 0.000307 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.94 |
Solubility | 0.27 mg/ml ; 0.00115 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.41 |
Solubility | 0.00927 mg/ml ; 0.0000394 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) |
Yes |
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 |
-5.55 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) |
1.8 |
* 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 N,N-dimethyl-formamide; | (iii) (3-chIoro-5-methoxyphenyl)acetonitrilePhosphorous tribromide (0.28 ml) was added to a solution of the product of step (ii) (1.55 g) in ether (20 ml) at 0 0C, then stirred for 30 min. The reaction mixture was partitioned between ether and aqueous sodium hydrogen carbonate, the organics were separated then dried (MgSO4) and evaporated under reduced pressure. The residue was dissolved in DMF (20 ml) and sodium cyanide (0.5 g) was added. The mixture was stirred overnight then partitioned between ether and water; the organics were separated, washed with aqueous sodium hydrogen carbonate then dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography (eluent 1:1 ether/ isohexane) to give the subtitle compound (0.53g).1H NMR CDCl3-d6: delta 6.91-6.9 (IH, m), 6.86-6.85 (IH, m), 6.77-6.76 (IH, m), 3.79 (3H, s), 3.69 (2H, s). | |
In N,N-dimethyl-formamide;Product distribution / selectivity; | (iii) (3-chloro-5-methoxyphenyl)acetonitrile Phosphorous tribromide (0.28 ml) was added to a solution of the product of step (ii) (1.55 g) in ether (20 ml) at 0 C., then stirred for 30 min. The reaction mixture was partitioned between ether and aqueous sodium hydrogen carbonate, the organics were separated then dried (MgSO4) and evaporated under reduced pressure. The residue was dissolved in DMF (20 ml) and sodium cyanide (0.5 g) was added. The mixture was stirred overnight then partitioned between ether and water; the organics were separated, washed with aqueous sodium hydrogen carbonate then dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography (eluent 1:1 ether/isohexane) to give the subtitle compound (0.53 g). 1H NMR CDCl3-d6: delta 6.91-6.9 (1H, m), 6.86-6.85 (1H, m), 6.77-6.76 (1H, m), 3.79 (3H, s), 3.69 (2H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With phosphorus tribromide; In diethyl ether; at 0 - 20℃; for 2h; | To a solution of (3-chloro-5-methoxyphenyl)methanol (2.0 g, 1 1 .6 mmol) in diethyl ether (20 ml_) at 0 C was added phosphorus tribromide (0.5 ml_). The reaction mixture was stirred at 0 C for 2 h. Reaction was poured into saturated aqueous sodium bicarbonate (150 ml_) and extracted with ethyl acetate (200 ml_ x 2). The combined organic phases were dried over sodium sulfate, filtered and concentrated to afford 1 -(bromomethyl)-3-chloro-5-methoxybenzene (2.15 g, 9.16 mmol, 79%) as a light-yellow solid. Used in the next step directly without additional purification. |
With phosphorus tribromide; In diethyl ether; at 0℃; for 0.5h; | (iii) (3-chIoro-5-methoxyphenyl)acetonitrilePhosphorous tribromide (0.28 ml) was added to a solution of the product of step (ii) (1.55 g) in ether (20 ml) at 0 0C, then stirred for 30 min. The reaction mixture was partitioned between ether and aqueous sodium hydrogen carbonate, the organics were separated then dried (MgSO4) and evaporated under reduced pressure. The residue was dissolved in DMF (20 ml) and sodium cyanide (0.5 g) was added. The mixture was stirred overnight then partitioned between ether and water; the organics were separated, washed with aqueous sodium hydrogen carbonate then dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography (eluent 1:1 ether/ isohexane) to give the subtitle compound (0.53g).1H NMR CDCl3-d6: delta 6.91-6.9 (IH, m), 6.86-6.85 (IH, m), 6.77-6.76 (IH, m), 3.79 (3H, s), 3.69 (2H, s). | |
With phosphorus tribromide; In diethyl ether; at 0℃; for 0.5h; | Phosphorous tribromide (0.28 ml) was added to a solution of the product of step (ii) (1.55 g) in ether (20 ml) at 0 C., then stirred for 30 min. The reaction mixture was partitioned between ether and aqueous sodium hydrogen carbonate, the organics were separated then dried (MgSO4) and evaporated under reduced pressure. The residue was dissolved in DMF (20 ml) and sodium cyanide (0.5 g) was added. The mixture was stirred overnight then partitioned between ether and water; the organics were separated, washed with aqueous sodium hydrogen carbonate then dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography (eluent 1:1 ether/isohexane) to give the subtitle compound (0.53 g). 1H NMR CDCl3-d6: delta 6.91-6.9 (1H, m), 6.86-6.85 (1H, m), 6.77-6.76 (1H, m), 3.79 (3H, s), 3.69 (2H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | To a solution of 2,4-dimethyl-2-(4-(2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)thiazol-2-yl)oxazole-5-carboxamide (0.050 g, 0.136 mmol) in anhydrous dimethylformamide (3 mL) in a flamed dried flask under argon atmosphere at 0 C. was added sodium hydride (60% in mineral oil, 0.014 g, 0.339 mmol) was added in one portion. The reaction was stirred for 10 min at 0 C. then <strong>[885270-32-6]1-(bromomethyl)-3-chloro-5-methoxybenzene</strong> (0.034 g, 0.143 mmol) was added as a solid in one portion. The mixture was stirred for 90 minutes, then 1 hour at room temperature. After consumption of starting material, the reaction mixture was quenched with saturated ammonium chloride (25 mL) and extracted with ethyl acetate (2*25 mL). The combined organics were washed once with saturated sodium bicarbonate (50 mL) and dried over anhydrous sodium sulfate. The concentrated residue was purified by flash chromatography over silica gel using 95:5 dichloromethane/methanol to give N-(4-(4-(1-(3-chloro-5-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)thiazol-2-yl)-2,4-dimethyloxazole-5-carboxamide (0.068 g, 96%) as beige solid. 1H NMR (400 MHz, DMSO-d): delta 12.52 (s, 1H), 7.81 (d, 1H, J=2.0 Hz), 7.70 (dd, 1H, J=8.4, 1.6 Hz), 7.58 (s, 1H), 6.98 (d, 1H, J=8.4 Hz), 6.90 (m, 1H), 6.86 (m, 1H), 6.78 (m, 1H), 5.13 (bs, 2H), 3.74 (s, 3H), 3.01 (m, 2H), 2.75 (m, 2H), 2.48 (s, 3H), 2.40 (s, 3H). MS (ESI): Calcd. for C26H23ClN4O4S: 523, found 524 (M+1)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In water; acetonitrile; at 80℃; for 1h; | General procedure: A mixture of 1 -bromo-3-(bromomethyl)benzene(2.2 g, 8.87 mmol), 5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-2-amine (2.2 g, 10.0 mmol), [1 ,1 '-b/s(diphenylphosphino)ferrocene]dichloropalladium(ll)-dichloromethane complex (0.361 g, 0.44 mmol), potassium carbonate (2.45 g, 17.7 mmol), acetonitrile (80 ml_) and water (16 ml_) was stirred at 80 C under nitrogen for 2 h. The mixture was poured into water, extracted with ethyl acetate (150 ml_ x 2). The combined organic phase was concentrated. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate = 1 /1 ) to afford compound 5-(3-bromobenzyl)pyridin-2-amine (1 .6 g, 6.10 mmol, 68.8%) as a light-yellow oil. |
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