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Chemical Structure| 5182-44-5 Chemical Structure| 5182-44-5

Structure of 5182-44-5

Chemical Structure| 5182-44-5

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Product Details of [ 5182-44-5 ]

CAS No. :5182-44-5
Formula : C8H9ClO
M.W : 156.61
SMILES Code : C1=C(C=CC=C1Cl)CCO
MDL No. :MFCD00002892
Boiling Point : No data available
InChI Key :NDWAVJKRSASRPH-UHFFFAOYSA-N
Pubchem ID :78856

Safety of [ 5182-44-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 5182-44-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 2
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 42.39
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

20.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.03
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

1.73
Log Po/w (WLOGP)?

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

1.87
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.

2.46
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

2.64
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.15

Water Solubility

Log S (ESOL):?

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

-2.21
Solubility 0.959 mg/ml ; 0.00613 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-1.77
Solubility 2.65 mg/ml ; 0.0169 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

-3.23
Solubility 0.0916 mg/ml ; 0.000585 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.

-6.03 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

2.0
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)

1.12

Application In Synthesis of [ 5182-44-5 ]

* 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 [ 5182-44-5 ]

[ 5182-44-5 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 5182-44-5 ]
  • [ 16799-05-6 ]
YieldReaction ConditionsOperation in experiment
71% With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 5h; Add triphenylphoshpine (3.90 g, 14.9 mmol) to a stirred solution of 3- chlorophenethyl alcohol (2.0 mL, 14.8 mmol), carbon tetrabromide (4.91 g, 14.8 mmol) and anhydrous dichloromethane (100 mL). Stir for 5 h under nitrogen at room temperature, and then wash with water (100 mL) and brine (100 mL). Dry the dichloromethane layer over magnesium sulfate, filter, and concentrate on a rotary evaporator to give the crude product. The crude product is purified by flash chromatography on silica gel eluting with 100% hexanes to yield 2. 30 g (71%) of 1- (2- bromo-ethyl) -3-chloro-benzene: TLC: Rf in 100% hexanes : 0.27 ; LH NMR (CDC13) : 7.26-7. 11 (m, 3H), 7.09-7. 07 (m, 1H), 3.54 (t, 2H), 3.12 (t, 2H).
64.6% Production Example 5 Synthesis of 3-chlorophenethyl bromide 3-Chlorophenethyl alcohol (1.0 ml) was treated as in Production Example 1 to give the title compound (1.417 g) as a pale yellow oil (yield: 64.6%). 1H-NMR (400 MHz, CDCl3): delta(ppm) 3.14(2H, t, J=8.6Hz), 3.56(2H, t, J=8.6Hz), 7.11(1H, m), 7.21(1H, s), 7.45(2H, m).
With bromotriphenylphosphonium bromide; In acetonitrile; for 24h; According to Scheme 11, a solution of 3-chlorophenethyl alcohol (5 g, 32 mmol) in 50 mL of dry MeCN was treated with dibromotriphenylphosphorane (13.54 g, 32 mmol) for 24 h. The reaction mixture was filtered and the solvent was removed in vacuo. The residue was triturated with hexane and filtered. Evaporation of the solvent provided 6.5 g of 3-chlorophenethyl bromide
22.4 g With phosphorus tribromide; at 0 - 80℃; for 2.16667h; Specific operations are as follows: 20g of m-chlorophenylacetic acid was added to 200ml of tetrahydrofuran, cooled to 0 C with stirring,At the beginning of batch addition of 8.9g of lithium aluminum hydride, the temperature was raised to 25 ~ 30 after the addition, the reaction 4h after the addition of water 300ml, dichloromethane400 ml of the mixture was separated, and the organic phase was added with 20 g of anhydrous sodium sulfate and dried under reduced pressure at 30-35 C. to obtain a pale yellow oil (S1-1): 18.3 g; Dropping phosphorus tribromide, the dropping temperature during the control at 0 ~ 10 C, dropping completed,After stirring for 10min, the temperature was raised to 75-80 C,After stirring for 2h, 30ml of saturated sodium bicarbonate solution, 200ml of ethyl acetate,The mixture was stirred for 20 minutes, and the filtrate was concentrated under reduced pressure at 40-45 C. to give a yellow liquid (intermediate S2): 22.4 g. Yield: 87.0%.

  • 2
  • [ 5182-44-5 ]
  • [ 16799-05-6 ]
  • [ 791-28-6 ]
YieldReaction ConditionsOperation in experiment
57% With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 18h;Product distribution / selectivity; To a solution of 2- (3-chlorophenyl) ethanol (1.06 g, 6.0 mmol) in CH2CL2 (50 mL) at RT under nitrogen was added CBr4 (1.98 g, 5.8 mmol) and PPh3 (1.57 g, 5.8 mmol). After stirring at RT for 18 h the reaction mixture was concentrated and the residue diluted with ETZO (30 mL) resulting in precipitation of triphenylphosphine oxide. The ethereal solution was decanted, evaporated and purified via flash chromatography (silica, hexane) to provide 2- (3-CHLORO) phenylethyl bromide as a clear oil (57%). 1H NMR (400 MHz, DMSO-d6) 8 7.39-7. 22 (m, 3 H), 7.18-7. 09 (m, 1 H), 3.63-3. 51 (m, 2 H), 3.25-3. 17 (m, 2 H); 13C NMR (100.6 MHz, DMSO-d6) B 141.2, 134.6, 130.7, 129.3, 127.6, 127.3.
  • 4
  • [ 3973-08-8 ]
  • [ 5182-44-5 ]
  • 3-chlorophenethyl thiazole-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
65.5% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0 - 20℃; for 5h; General procedure: 2.5mmol thiazole-4-carboxyli acid and 2.0mmol alcohol were dissolved in 25mL dichloromethane (DCM) in a dry flask with continuous stirring, followed by the addition of 2.5mmol 3-(3-dimethylaminopropyl) -1-ethylcarbodiimide hydrochloride. When the temperature of the reaction system cooled to 0°C, 0.2mmol 4-dimethylaminopyridine was added dropwise and reacted for 1hat 0°C. Then the temperature was elevated to room temperature for another 4h reaction. The reaction was stopped by adding 25mL saturated NaHCO3 solution and extracted twice with 20mL dichloromethane (2×20mL). The extracted organic layers were first dried by anhydrous Na2SO4, and then filtered and concentrated under vacuum distillation, obtaining the crude products. Finally, the crude products were further purified using column chromatography (ethy lacetate:petroleum ether, 1:5).
 

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