Structure of 199177-26-9
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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. : | 199177-26-9 |
Formula : | C7H5BrO2 |
M.W : | 201.02 |
SMILES Code : | O=CC1=CC(O)=CC(Br)=C1 |
MDL No. : | MFCD06797981 |
Boiling Point : | No data available |
InChI Key : | XVFGERBEZKEGSS-UHFFFAOYSA-N |
Pubchem ID : | 16641084 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 41.55 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.35 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.5 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.97 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.55 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.18 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.91 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.04 |
Solubility | 0.184 mg/ml ; 0.000913 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.93 |
Solubility | 0.237 mg/ml ; 0.00118 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.63 |
Solubility | 0.473 mg/ml ; 0.00236 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 |
-5.75 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 |
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) |
1.36 |
* 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 boron tribromide; In dichloromethane; at -78 - 20℃; for 2h; | A solution of BBr3 (29.1 mL of a 1.0 M solution in DCM, 29.1 mmol) was added slowly to a solution of 170a (2.5 g, 11.62 mmol) in anhydrous DCM (25 mL) maintained under N2 at -78 C. The orange solution was warmed to RT, stirred for 2 h, and poured onto ice. The mixture was extracted with CH2Cl2 (100 mL), and the organic layer was washed with H2O (50 mL) and brine (50 mL). The solvents were evaporated, and the remaining oil was purified by flash chromatography on silica gel eluting with a EtOAc/hexanes gradient (0% to 20% EtOAc) to provide the desired phenol. To a solution of this phenol in pyridine (10 mL) under argon was slowly added acetic anhydride (0.6 mL, 6.33 mmol). After 2 h, the volatile materials were removed to provide 3-bromo-5-formyl-phenyl acetate (170b, 1.02 g, 40%). | |
With boron tribromide; In dichloromethane; at -78 - 20℃; for 2h; | step 1-A solution of BBr3 (29.1 mL of a 1.0 M solution in DCM, 29.1 mmol) was added slowly to a solution of 45a (2.5 g, 11.62 mmol) in anhydrous DCM (25 mL) maintained under N2 at -78 C. The orange solution was warmed to RT, stirred for 2 h, and poured onto ice. The mixture was extracted with DCM (100 mL), and the organic layer was washed with H2O (50 mL) and brine (50 mL). The solvents were evaporated, and the remaining oil was purified by flash chromatography on SiO2 eluting with an EtOAc/hexane gradient (0% to 20% EtOAc) to provide the desired phenol. To a solution of this phenol in pyridine (10 mL) under argon was slowly added acetic anhydride (0.6 mL, 6.33 mmol). After 2 h, the volatile materials were removed to provide 3-bromo-5-formyl-phenyl acetate (45b, 1.02 g, 40 %). | |
With boron tribromide; In dichloromethane; at -78 - 20℃; for 2h; | A solution of BBr3 (29.1 mL of a 1.0 M solution in DCM, 29.1 mmol) was added slowly to a solution of 62a (2.5 g, 11.62 mmol) in anhydrous DCM (25 mL) maintained under N2 at -78 C. The orange solution was warmed to RT, stirred for 2 h, and poured onto ice. The mixture was extracted with CH2Cl2 (100 mL), and the organic layer was washed with H2O (50 mL) and brine (50 muL). The solvents were evaporated, and the remaining oil was purified by flash chromatography on silica gel eluting with a EtOAc/hexanes gradient (0% to 20% EtOAc) to provide the desired phenol. To a solution of this phenol in pyridine (10 mL) under argon was slowly added acetic anhydride (0.6 mL, 6.33 mmol). After 2 h, the volatile materials were removed to provide 3-bromo-5-formyl-phenyl acetate (62b, 1.02 g, 40%). |
With boron tribromide; In dichloromethane; at -78 - 20℃; for 2h; | A solution of BBr3 (29.1 mL of a 1.0 M solution in DCM, 29.1 mmol) was added slowly to a solution of R-17a (2.5 g, 11.62 mmol, CAS Reg. No. 262450-65-7) in anhydrous DCM (25 mL) maintained under N2 at -78 C. The orange solution was warmed to RT, stirred for 2 h, and poured onto ice. The mixture was extracted with DCM (100 mL), and the organic layer was washed with H2O (50 mL) and brine (50 mL). The solvents were evaporated, and the remaining oil was purified by SiO2 chromatography eluting with a EtOAc/hexanes gradient (0% to 20% EtOAc) to provide the desired phenol. To a solution of this phenol in pyridine (10 mL) under argon was slowly added acetic anhydride (0.6 mL, 6.33 mmol). After 2 h, the volatile materials were removed to provide 3-bromo-5-formyl-phenyl acetate (R-17b, 1.02 g, 40%). | |
With boron tribromide; In dichloromethane; at -78 - 20℃; for 2h; | step 1-A solution of BBr3 (29.1 mL of a 1.0 M solution in DCM, 29.1 mmol) was added slowly to a solution of R-17a (2.5 g, 11.62 mmol, CASRN 262450-65-7) in anhydrous DCM (25 mL) maintained under N2 at -78 C. The orange solution was warmed to RT, stirred for 2 h, and poured onto ice. The mixture was extracted with DCM (100 mL), and the organic layer was washed with H2O (50 mL) and brine (50 mL). The solvents were evaporated, and the remaining oil was purified by SiO2 chromatography eluting with a EtOAc/hexanes gradient (0% to 20% EtOAc) to provide the desired phenol. To a solution of this phenol in pyridine (10 mL) under argon was slowly added acetic anhydride (0.6 mL, 6.33 mmol). After 2 h, the volatile materials were removed to provide 3-bromo-5-formyl-phenyl acetate (R-17b, 1.02 g, 40%). | |
A solution of BBr3 (29.1 mL of a 1.0 M solution in CH2Cl2, 29.1 mmol) was added slowly to a solution of 119 (2.5 g, 11.62 mmol) in anhydrous CH2Cl2 (25 mL) under nitrogen at -78 C. The orange solution was warmed to RT, stirred for 2 h, and poured onto ice. The mixture was extracted with CH2Cl2 (100 mL), and the organic layer was washed with H2O (50 mL) and brine (50 mL). The solvents were evaporated, and the remaining oil was purified by flash chromatography on silica gel (0% to 20% EtOAc/hexanes) to provide the desired phenol. To a solution of this phenol in pyridine (10 mL) under argon was slowly added acetic anhydride (0.6 mL, 6.33 mmol). After 2 h, the volatile materials were removed to provide 3-bromo-5-formyl-phenyl acetate (120, 1.02 g, 40%). | ||
With boron tribromide; In dichloromethane; at -78 - 20℃; for 2h; | step 1-A solution of BBr3 (29.1 mL of a 1.0 M solution in DCM, 29.1 mmol) was added slowly to a solution of 27a (2.5 g, 11.62 mmol) in anhydrous DCM (25 mL) maintained under N2 at -78 C. The orange solution was warmed to RT, stirred for 2 h, and poured onto ice. The mixture was extracted with DCM (100 mL), and the organic layer was washed with H2O (50 mL) and brine (50 mL). The solvents were evaporated, and the remaining oil was purified by flash chromatography on silica gel eluting with a EtOAc/hexanes gradient (0% to 20% EtOAc) to provide the desired phenol. To a solution of this phenol in pyridine (10 mL) under argon was slowly added acetic anhydride (0.6 mL, 6.33 mmol). After 2 h, the volatile materials were removed to provide 3-bromo-5-formyl-phenyl acetate (27b, 1.02 g, 40%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With sodium hydride; In N,N-dimethyl-formamide; at 0 - 20℃; | Example 1 5A: 3 -Bromo-5-methoxybenzaldehyde j00295j 3-Bromo-5-hydroxybenzaldehyde (0.5 g, 2.487 mmol) was dissolved in DMF(14.63 mL) and cooled to 0 C. NaH (0.119 g, 4.97 mmol) was added in three portions.The flask was immediately allowed to warm to ambient temperature and Mel (0.93 3 mL,14.92 mmol) was added, and the reaction stirred overnight. The reaction was diluted with water and partially concentrated in vacuo. The material was diluted with DCM and washed twice with water, washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude material was purified by silica gel column chromatography (gradientfrom 0 to 100% EtOAc in hexanes) to yield Example 15A (0.488 g, 2.27 mmol, 9 1%).?H NMR (400 MHz, CHLOROFORM-cl) oe ppm 9.91 (1 H, s), 7.58 (1 H, t, J=1.38 Hz), 7.28 - 7.35 (2 H, m, J=2.38, 2.13, 2.01, 2.01 Hz), 3.86 (3 H, s). |
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