Structure of 51760-22-6
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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. : | 51760-22-6 |
Formula : | C8H9BrO2 |
M.W : | 217.06 |
SMILES Code : | OCC1=CC(CO)=CC(Br)=C1 |
MDL No. : | MFCD00229250 |
InChI Key : | IZWWAHXLUWAJRC-UHFFFAOYSA-N |
Pubchem ID : | 14383229 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 46.4 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.88 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.84 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.13 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.68 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.19 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.55 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.99 |
Solubility | 2.24 mg/ml ; 0.0103 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.27 |
Solubility | 11.6 mg/ml ; 0.0534 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.92 |
Solubility | 0.263 mg/ml ; 0.00121 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 |
-7.03 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) |
1.48 |
* 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 |
---|---|---|
85% | With dimethylsulfide borane complex; In tetrahydrofuran; at 0 - 20℃;Inert atmosphere; | <strong>[23351-91-9]5-bromoisophtalic acid</strong> (25.0 gram, 0.102 mol, 1 equiv) was dissolved in dry THF (500 mL) at 0 °C under argon atmosphere. 10M Borane dimethylsulfide complex (50 mL, 0.50 mmol, 5 equiv) was added and the mixture was stirred at room temperature overnight. H20 (1000 mL) was added carefully to the mixture followed by addition of EtOAc (1000 mL). After separation of the layers, the organic layer was washed with H20 (3 >< 750 mL) and brine (1000 mL). The organic layer was dried over MgSO4, filtered and (0296) concentrated in racuo yielding alcohol 7 as a white powder in 85percent yield with no need for further purification. 1H NMR (400 MHz, DMSO) 8 7.36 (s, 2H), 7.25 (s, 1H), 5.30 (t, 2H), 4.48 (d, 4H). 13C NMR (400 MHZ, DMSO) 6 145.2, 127.1, 123.1, 121.3, 62.1. IR V 3210, 2851, 1602, 1419 cm-1. HRMS (FD+) m/z caIcuIated for C8H9BrOz 215.9786, found 215.9798. Spectral data in agreement with reported data (Wytko and Weiss, 1994). |
81% | With sodium tetrahydroborate; boron trifluoride diethyl etherate; In tetrahydrofuran; at 20℃; for 2h;Inert atmosphere; Cooling with ice; | A solution of <strong>[23351-91-9]5-bromoisophthalic acid</strong> (5 g, 20.4 mmol) in tetrahydrofuran (80 ml) was added to a solution of sodium borohydride (2.76 g, 73.0 mmol) in tetrahydrofuran (20 ml) under an argon atmosphere and ice cooling, followed by stirring. Boron trifluoride diethyl ether complex (7.6 ml, 60.9 mmol) was added over 1 hour while cooling on ice, and the temperature was returned to room temperature and stirred for 1 hour. A 0.5 mol/l sodium hydroxide aqueous solution (40 ml) was added to the reaction solution, and the mixture was extracted with ethyl acetate. The aqueous layer was further extracted twice with ethyl acetate, the organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified on a column to give (5-bromo-1,3-phenylene) dimethanol (3.60 g, 81percent) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.3% | With sodium tetrahydroborate; In tetrahydrofuran; methanol; at 0℃; for 5.0h;Cooling with ice; | A three-necked flask having a capacity of 2 liters was charged with 109.2g of dimethyl 5-bromo-isophthalate and then with 400 ml of tetrahydrofuran (THF), to prepare a solution of dimethyl 5-bromoisophthalate. The solution was mixed with 16.6g of sodium borohydride and the resultant mixture liquid was agitated while cooling the mixture liquid with ice pieces. Separately, 40.5 ml of methyl alcohol were dissolved in 150 ml of THF, the resultant solution was mixed in the ice-cooled mixture liquid. Then, the resultant reaction mixture liquid was agitated for 5 hours while cooling with ice pieces. The reaction mixture liquid was added with 380 ml of water to terminate the reaction, and then mixed with a 1 mole hydrochloric acid solution to adjust the pH value of the reaction mixture liquid to 7.0. The resultant reaction mixture liquid was subjected to an extraction treatment with 380 ml of ethyl acetate and then with 200 ml of ethyl acetate. The resultant organic extract liquids were mixed with each other, and the resultant mixed extract liquid was washed with 300 ml of water and then with 80 ml of a saturated aqueous common salt solution, and the resultant washed extract liquid was dried with a drying agent consisting of anhydrous magnesium sulfate. The dried extract liquid was filtered to separate the drying agent, and the resultant filtrate was concentrated. A crude product of the target compound, namely methyl 5-bromo-3-(hydroxymethyl)benzoate was obtained in an amount of 96.5g. In the crude product, the mass ratio of the target compound, namely methyl 5-bromo-3-(hydroxymethyl)benzoate to the by-product consisting of 5-bromo-3-(hydroxymethyl)benzyl alcohol was 88:10, as determined by NMR measurement. The crude product was dissolved in 160 ml of methyl alcohol; the resultant solution was placed in a separatory funnel and mixed with 160 ml of water and 1000 ml of xylene; and the resultant mixture liquid was subjected to a phase separation. The resultant organic phase fraction was collected, washed with 160 ml of a solution of methyl alcohol in water in volume ratio of 1:1, then with 160 ml of water and finally with 160 ml of a saturated aqueous common salt solution. The washed organic phase fraction was dried with a drying agent consisting of anhydrous magnesium sulfate. The dried solution was subjected to a filtration procedure to remove the drying agent from the organic phase fraction. Then, the filtrate was concentrated. The target compound, namely, purified methyl 5-bromo-3-(hydroxymethyl)benzoate was obtained in an amount of 81.98g. The yield thereof was 83.3%. In the resultant purified product, a mass ratio of the target compound, methyl 5-bromo-3-(hydroxymethyl)benzoate to a by-product, namely, 5-bromo-3-(hydroxymethyl)benzyl alcohol was 96:1.8, determined by the NMR measurement. The results of the 1H-NMR measurement (200 MHz, delta ppm, CDCl3) were as follows 3.93(s, 3H), 4.74 (d, J = 5.6 Hz, 2H) 7.73 (s, 1H), 7.95 (s, 1H), 8.09 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃;Inert atmosphere; Cooling with ice; | A solution of (5-bromo-1 ,3-phenylene)dimethanol (CAS 51760-22-6) (32.5 g, 150 mmol) and ferf-butyl 2-(2-hydroxyphenyl)acetate (Intermediate 21 ) (15.6 g, 74.9 mmol) and PPh3 (39.3 g, 150 mmol) in THF (250 mL) was cooled to 0 C in an ice/water bath. DIAD (29.1 mL, 150 mmol) was added dropwise and the resulting yellow solution was allowed to warm to room temperature. After overnight the reaction was quenched with water, extracted with EtOAc, dried with MgS04, filtered and concentrated. The crude product was purified by flash chromatography (0-60% EtOAc: Heptanes) to provide the title compound. 1H NMR (600 MHz, DMSO-c/6) delta ppm 7.50 (s, 1 H) 7.46 (s, 1 H) 7.36 (s, 1 H) 7.16 - 7.27 (m, 2 H) 7.01 (d, J=8.07 Hz, 1 H) 6.91 (td, J=7.40, 0.87 Hz, 1 H) 5.34 (t, J=5.73 Hz, 1 H) 5.1 1 (s, 2 H) 4.50 (d, J=5.69 Hz, 2 H) 3.55 (s, 2 H) 1.34 (s, 9 H). | |
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; | Intermediate 13-A. ferf-Butyl 2-(2-((3-bromo-5-(hydroxymethyl)benzyl)oxy)phenyl)acetate A solution of (5-bromo-1 ,3-phenylene)dimethanol (CAS 51760-22-6) (32.5 g, 150 mmol) and fe/f-butyl 2-(2-hydroxyphenyl)acetate (Intermediate 2) (15.6 g, 74.9 mmol) and PPh3 (39.3 g, 150 mmol) in THF (250 mL) was cooled to 0 C in an ice/water bath. DIAD (29.1 ml_, 150 mmol) was added dropwise and the resulting yellow solution was allowed to warm to room temperature and stirred overnight. Excess base was quenched with water, the resulting mixture was extracted with EtOAc, dried with MgS04, filtered and concentrated. The residue was purified by silica gel chromatography (0-60% EtOAc/heptane) to provide the title compound. 1H NMR (600 MHz, DMSO-c/6) delta ppm 7.50 (s, 1 H) 7.46 (s, 1 H) 7.36 (s, 1 H) 7.16 - 7.27 (m, 2 H) 7.01 (d, J=8.07 Hz, 1 H) 6.91 (td, J=7.40, 0.87 Hz, 1 H) 5.34 (t, J=5.73 Hz, 1 H) 5.1 1 (s, 2 H) 4.50 (d, J=5.69 Hz, 2 H) 3.55 (s, 2 H) 1 .34 (s, 9 H). |