Structure of 329218-12-4
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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. : | 329218-12-4 |
Formula : | C7H6BrClO |
M.W : | 221.48 |
SMILES Code : | OCC1=CC(Br)=C(Cl)C=C1 |
MDL No. : | MFCD08059085 |
InChI Key : | ZUXLQZNUPRSYEX-UHFFFAOYSA-N |
Pubchem ID : | 50998689 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | 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 | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 45.28 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.19 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.8 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.44 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.99 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.66 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.36 |
Solubility | 0.0978 mg/ml ; 0.000441 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.88 |
Solubility | 0.291 mg/ml ; 0.00131 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.7 |
Solubility | 0.044 mg/ml ; 0.000199 mol/l |
Class? Solubility class: Log S scale |
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 |
-5.66 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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.45 |
* 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 |
---|---|---|
100% | With borane-THF; In tetrahydrofuran; at 0 - 20℃;Inert atmosphere; | A. (3-Bromo-4-chloro-phenyl)-methanolTo a mixture of <strong>[42860-10-6]3-bromo-4-chloro-benzoic acid</strong> (10.0 g, 42.5 mmol) in THF (50 mL) under nitrogen at 0 °C is added 1 .0 M solution of borane.THF (55.3 mL, 55.3 mmol). After stirring at ambient temperature overnight the reaction is poured into a mixture of NaHCO3/H2O/ice and extracted with EtOAc. The organic layer is washed with saturated aqueous NaCI, dried over MgSO4, filtered and concentrated in vacuo to provide the desired product (9.4 g, 100percent) as a clear, colorless oil.1 H NMR (300 MHz, CDCI3) delta 7.61 (s, 1 H), 7.41 (d, J = 5.1 Hz, 1 H), 7.21 (d, J = 5.1 Hz, 1 H), 4.63 (s, 2H), 2.12 (br s, 1 H). |
92% | With dimethylsulfide borane complex; In tetrahydrofuran; at 20℃; | General procedure: <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> (34.2 g, 145.25 mmol) was dissolved in THF (250 ml)and cooled to 0 °C, to this was added borane-methyl sulfide complex (153 ml,305.02 mmol) and the reaction was warmed to room temperature and stirred overthe weekend. The reaction was very carefully quenched with saturated Na2CO3 (100mL), extracted with EtOAc (3 x 100 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford a colourless liquid. The crude product was purifiedby distillation at 0.2 mBar, collecting fractions that distilled at 100 °C to afford (3-bromo-4-chlorophenyl)methanol (29.5 g, 92 percent) as a colourless liquid. |
90% | With dimethylsulfide borane complex; In tetrahydrofuran; at 0 - 80℃; for 1.5h;Reflux; | Example 6, Step 1To a solution of 3-bromo-4-benzoic acid 6-1 (4.0 g, 17.0 mmol) in anhydrous TI{F (18 mL) was slowly added BH3.DMS (1.6 g, 20.4 mmol) at 0°C then the reaction was refluxed at 80°C for 90 mm. The mixture was cooled and concentrated in vacuo, diluted with water and extracted with DCM. The organic layer was washed with saturated aqueous sodium bicarbonate solution then brine, dried over Na2SO4 and concentrated in vacuo. The residue waspurified by chromatography over silica gel (eluting with hexanes/EtOAc 100:0 to 0:100) to afford 3.4 g (90percent) of intermediate 6-2. |
Example 12 4-Aminomethyl-cyclohexanecarboxylic acid {1-[3-(3-amino-1H-indazol-6-yl)-4-chloro-phenyl]-2-phenyl-ethyl}-amide 12A. 3-Bromo-4-chloro-benzaldehyde: To a cooled (0° C.), clear, colorless solution of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> (1.0 g, 4.25 mmol) in THF (43 mL) was added dropwise a 1.0 M borane-THF complex (12.7 mL, 12.7 mmol). After 15 min, the reaction was warmed to rt and then to reflux. After 2 h, the reaction was cooled to rt, then to 0° C., and then quenched with MeOH (10 mL). The reaction was warmed to rt and after 15 min., the reaction was concentrated. The residue was dissolved in EtOAc and washed with 1.0 N HCl, sat. NaHCO3, brine, dried over Na2SO4, filtered and concentrated to give a clear, colorless liquid. The liquid was dissolved in CH2Cl2 (17 mL) and cooled to 0° C. Next Dess-Martin periodinane (2.16 g, 5.10 mmol) was added. The resulting cloudy pale orange suspension was stirred for 30 min. and then diluted with Et2O (50 mL). The reaction was filtered through a plug of silica gel and the filtrate was concentrated to give an off-white solid. Column chromatography on silica gel (gradient elution 0-25percent EtOAc in Hex) gave 0.815 g (87percent) of the aldehyde as a white solid. 1H NMR (400 MHz, CDCl3) delta: 9.94 (s, 1H), 8.13 (d, J=1.8 Hz, 1H), 7.77 (dd, J=8.1, 2.0 Hz, 1H), 7.63 (d, J=7.9 Hz, 1H). | ||
With borane; In tetrahydrofuran; at 65℃; for 12h; | A solution of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> (3.53 g, 15 mmol) was dissolved in anhydrous THF (20 [ML)] and cooled to 0 C prior to addition of borane [(1M] soln in [THF,] 20 mL, 20 mmol). The solution was then heated at 65 C for 12 hours then cooled to 0 C and methanol was added dropwise to quench excess borane. The solvent was evaporated under reduced pressure, the residue was redissolved in ethyl acetate and washed with saturated NH4Cl then brine, dried over sodium sulphate. The solvent was removed in vacuo to afford 3.23 g of title compound. [ <P>C7H6BRC10] Mass (calculated): [221], [MH NOT] found. NMR (400 MHz, CDC13) : 4.6 (2H, s, CH20H); 7.15 [(1H,] dd, [J=] 1 and 8 Hz, aryl- H); 7.35 [(1H,] d, [J =] 8 Hz, aryl-H); 7.55 [(1H,] d, [J = 1 HZ,] aryl-H). | |
Step 1:199.0 g (0.845 mol) of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> were dissolved in 2.5 litres of THF, the mixture was cooled to -10° C. and 1.69 litres (1.69 mol) of a 1 M solution of borane in THF were added at this temperature. The reaction mixture was warmed to RT overnight, and saturated aqueous ammonium chloride solution was then added. After the addition of water, the mixture was extracted twice with ethyl acetate and the combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. This gave, as a crude product, 206 g of (3-bromo-4-chlorophenyl)methanol which were used in the subsequent step without further purification. | ||
Example 28A2-Bromo-4-(bromomethyl)-1-chlorobenzene Step 1:199.0 g (0.845 mol) of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> were dissolved in 2.5 litres of THF, the mixture was cooled to -10° C. and 1.69 litres (1.69 mol) of a 1 M solution of borane in THF were added at this temperature. The reaction mixture was warmed to RT overnight, and saturated aqueous ammonium chloride solution was then added. After addition of water, the mixture was extracted twice with ethyl acetate. The combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. This gave 206 g of (3-bromo-4-chlorophenyl)methanol as a crude product which was reacted without further purification. | ||
With borane-THF; In tetrahydrofuran; at -10 - 20℃; | Step 1: [0430] 199.0 g (0.845 mol) of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> were dissolved in 2.5 litres of THF, the solution was cooled to ?10° C. and 1.69 litres (1.69 mol) of a 1 M solution of borane in THF were added at this temperature. The reaction mixture was warmed to RT overnight, and saturated aqueous ammonium chloride solution was then added. After addition of water, the mixture was extracted twice with ethyl acetate, and the combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. This gave, as a crude product, 206 g of (3-bromo-4-chlorophenyl)methanol which were used without further purification for the next step. |
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