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Chemical Structure| 51760-22-6

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Product Details of [ 51760-22-6 ]

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

Safety of [ 51760-22-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 51760-22-6 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

40.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.88
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.84
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.13
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.68
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.19
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.55

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.99
Solubility 2.24 mg/ml ; 0.0103 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.27
Solubility 11.6 mg/ml ; 0.0534 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-2.92
Solubility 0.263 mg/ml ; 0.00121 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-7.03 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.48

Application In Synthesis of [ 51760-22-6 ]

* 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.

  • Downstream synthetic route of [ 51760-22-6 ]

[ 51760-22-6 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 23351-91-9 ]
  • [ 51760-22-6 ]
YieldReaction ConditionsOperation 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.
  • 2
  • [ 51760-21-5 ]
  • [ 307353-32-8 ]
  • [ 51760-22-6 ]
YieldReaction ConditionsOperation 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).
  • 3
  • [ 51760-22-6 ]
  • [ 258331-10-1 ]
  • tert-butyl 2-(2-((3-bromo-5-(hydroxymethyl)benzyl)oxy)phenyl)acetate [ No CAS ]
YieldReaction ConditionsOperation 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).
 

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