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Chemical Structure| 1208-87-3 Chemical Structure| 1208-87-3

Structure of 1208-87-3

Chemical Structure| 1208-87-3

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Product Details of [ 1208-87-3 ]

CAS No. :1208-87-3
Formula : C13H11ClS
M.W : 234.74
SMILES Code : ClCC1=CC=C(SC2=CC=CC=C2)C=C1
MDL No. :MFCD09907764
InChI Key :RLFHPRWHJYDGSD-UHFFFAOYSA-N
Pubchem ID :71022

Safety of [ 1208-87-3 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H314
Precautionary Statements:P260-P264-P270-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P405-P501
Class:8
UN#:3265
Packing Group:

Computational Chemistry of [ 1208-87-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 12
Fraction Csp3 0.08
Num. rotatable bonds 3
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 66.77
TPSA ?

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

25.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.89
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

4.38
Log Po/w (WLOGP)?

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

4.42
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.

4.95
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

4.59
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

4.25

Water Solubility

Log S (ESOL):?

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

-4.45
Solubility 0.00835 mg/ml ; 0.0000356 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-4.63
Solubility 0.00553 mg/ml ; 0.0000236 mol/l
Class?

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

Moderately 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

-6.05
Solubility 0.000208 mg/ml ; 0.000000887 mol/l
Class?

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

Poorly 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

Yes
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

Yes
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.

-4.62 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

1.0
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

1.0
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

1.0 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<2.0
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)

1.69

Application In Synthesis of [ 1208-87-3 ]

* 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 [ 1208-87-3 ]

[ 1208-87-3 ] Synthesis Path-Downstream   1~23

  • 3
  • [ 6317-56-2 ]
  • [ 1208-87-3 ]
YieldReaction ConditionsOperation in experiment
97.7% With pyridine; thionyl chloride; In dichloromethane; at 20 - 25℃; for 2h;Cooling with ice; 518.0 g of 4-phenylmercaptobenzyl alcohol, 147 ml of pyridine and 2444 ml of dichloromethane were charged into a 5000 mL reaction flask at room temperature (25 ° C.), and the mixture was cooled in ice water to control the temperatureThionyl chloride was added dropwise at 20-24 ° C and the mixture was stirred at room temperature (25 ° C) for 2 hours. TLC (n-hexane: ethyl acetate = 10: 1) was carried out to the end of the reaction. Washed with water, neutralized with water, dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure (pressure 1720 Pa, temperature 25 ° C) to dryness. Methylene chloride was recovered to obtain 548.0 g of brownish red oil with a yield of 97.7percent and HPLC purity of 99.66 percent. (Frozen to about -10 curable).
97.7% With pyridine; thionyl chloride; In dichloromethane; at 20 - 25℃; for 2h; 51 8.0 g of 4-phenylmercaptobenzyl alcohol at room temperature (25 °C),147 ml of pyridine and 2444 ml of dichloromethane were placed in a 5000 mL reaction flask, and thionyl chloride was added dropwise at a temperature of 20 to 24 °C under ice-cooling, and stirred at room temperature (25 °C) for 2 hours. Thin layer detection (n-hexane: acetic acid) Ethyl ester = 10:1) to the end of the reaction. The mixture was washed with water until neutral, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated to dryness under reduced pressure (pressure: 1720 Pa, temperature 25 °C), and dichloromethane was recovered to give a brownish red oil, 548.0 g, yield 97.7percent, HPLC purity: 99.66percent. (Chilled to about -10 °C to cure).
96.7% With pyridine; thionyl chloride; In dichloromethane; at 20 - 24℃; for 2.5h; The 4-benzoquinone benzyl alcohol, pyridine, and dichloromethane were put into the reaction flask at room temperature (25 °C), ice-cooled and cooled at 20-24 °C, thionyl chloride was added dropwise, and the mixture was stirred at 25° C for 2 hours. Thin layer detection (n-hexane:ethyl acetate=10:1) to the end of the reaction, washing with water to neutrality, drying the dichloromethane layer over anhydrous magnesium sulfate, filtering, and depressurizing the filtrate (pressure 1720 Pa, temperature 25 °C) To dryness, the methylene chloride was recovered to give a brown-red oil (frozen to about -10 °C or so). See Table 4 for details
With thionyl chloride; sodium hydrogencarbonate; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; dichloromethane; 2) Dissolving 3.0 g of 1-hydroxymethyl-4-phenylthiobenzene in 15 ml of methylene chloride, 1.5 ml of thionyl chloride was added while stirring in ice-cooling. After stirring for 1 hour, the reaction mixture was washed in ice water (10 ml*3), and 50 ml of methylene chloride was added. The mixture was sequentially washed with aqueous solution of 5percent sodium hydrogencarbonate (5 ml*3) and saturated brine (30 ml*2), and dried with anhydrous sodium sulfate, and concentrated in vacuo, thereby obtaining 1-chloromethyl-4-phenylthiobenzene (3.0 g). NMR (CDCl3) delta: 7.25~7.35 (m, 9H), 4.54 (s, 2H)
With thionyl chloride; In dichloromethane; (2) The 1-hydroxymethyl-4-phenylthiobenzene (3.0 g) is dissolved in methylene chloride (15 ml), and thereto is added with stirring thionyl chloride (1.5 ml) under ice cooling. The mixture is stirred for one hour, and the reaction mixture is washed with ice water (10 ml*3), and thereto is added methylene chloride (50 ml). The mixture is washed in order with 5percent aqueous sodium hydrogen carbonate solution (5 ml*3) and saturated aqueous sodium chloride solution (30 ml*2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 1-chloromethyl-4-phenylthiobenzene (3.0 g). NMR (CDCl3) delta: 7.25-7.35 (m, 9H), 4.54 (s, 2H)

  • 4
  • [ 1208-87-3 ]
  • [ 24155-42-8 ]
  • 1-(β-hydroxyethyl-β,2,4-dichlorophenylethyl)-3-(4-phenylthiobenzyl)imidazolium chloride [ No CAS ]
  • 5
  • [ 1208-87-3 ]
  • [ 24155-42-8 ]
  • 1-(β-hydroxyethyl-β,2,4-dichlorophenylethyl)-3-(4-phenylthiobenzyl)imidazolium chloride [ No CAS ]
  • 1-<β-(2,4-dichlorophenyl)-β-(4-phenylthiobenzyloxy)-ethyl>-3-(4-phenylthiobenzyl)imidazolium chloride [ No CAS ]
  • α-(2,4-dichlorophenyl)-β,N-imidazolylethyl 4-phenylthiobezyl ether nitrate [ No CAS ]
  • 6
  • [ 1208-87-3 ]
  • [ 24155-42-8 ]
  • [ 72479-26-6 ]
  • 7
  • [ 1208-87-3 ]
  • [ 24155-42-8 ]
  • 1-(β-hydroxyethyl-β,2,4-dichlorophenylethyl)-3-(4-phenylthiobenzyl)imidazolium chloride [ No CAS ]
  • 1-<β-(2,4-dichlorophenyl)-β-(4-phenylthiobenzyloxy)-ethyl>-3-(4-phenylthiobenzyl)imidazolium chloride [ No CAS ]
  • [ 72479-26-6 ]
  • 8
  • [ 1208-87-3 ]
  • [ 72479-26-6 ]
  • 1-<β-(2,4-dichlorophenyl)-β-(4-phenylthiobenzyloxy)-ethyl>-3-(4-phenylthiobenzyl)imidazolium chloride [ No CAS ]
  • 9
  • [ 50-00-0 ]
  • [ 139-66-2 ]
  • [ 1208-87-3 ]
  • 10
  • [ 1208-87-3 ]
  • [ 1208-88-4 ]
  • 12
  • [ 1208-87-3 ]
  • [ 591742-16-4 ]
  • [ 655243-98-4 ]
  • 13
  • [ 6310-24-3 ]
  • [ 1208-87-3 ]
  • 14
  • [ 1208-87-3 ]
  • 1-<β-(2,4-dichlorophenyl)-β-(4-phenylthiobenzyloxy)-ethyl>-3-(4-phenylthiobenzyl)imidazolium chloride [ No CAS ]
  • 15
  • [ 1208-87-3 ]
  • α-(2,4-dichlorophenyl)-β,N-imidazolylethyl 4-benzenesulfinylbenzyl ether [ No CAS ]
  • 16
  • [ 1208-87-3 ]
  • α-(2,4-dichlorophenyl)-β,N-imidazolylethyl 4-benzenesulfonylbenzyl ether [ No CAS ]
  • 17
  • [ 1208-87-3 ]
  • [ 6317-59-5 ]
YieldReaction ConditionsOperation in experiment
In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; N,N-dimethyl-formamide; 3) Dissolving 3.0 g of <strong>[1208-87-3]1-chloromethyl-4-phenylthiobenzene</strong> (3.0 g) in 15 ml of N,N-dimethylformamide, 1.0 g of finely ground sodium cyanide was added and stirred for 17 hours at room temperature. To the reaction mixture, 50 ml of saturated brine and 50 ml of ice water were added, and the mixture was extracted with ethyl acetate (100 ml*3). The extract was washed with saturated brine (50 ml*3), and dried with anhydrous sodium sulfate, and concentrated in vacuo, and 1-cyano-methyl-4-phenylthiobenzene was obtained (2.9 g). NMR (CDCl3) delta: 7.29~7.38 (m, 9 H), 3.7 1 (s, 2H)
  • 18
  • [ 1208-87-3 ]
  • [ 57489-79-9 ]
  • [ 189018-63-1 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; Production Example 81 Preparation of 4-(4-phenylthio)benzyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidine Potassium carbonate (1.5 g) and <strong>[1208-87-3]4-phenylthiobenzyl chloride</strong> (2.8 g) were added to a solution of 1.3 g of 7-hydroxypyrazolo[1,5-a]pyrimidine in 30 ml of DMF and stirred at 60° C. for 4 hours. The reaction mixture was diluted with ethyl acetate and washed with water and a saturated sodium chloride solution. The solvent was distilled off and the crude crystals obtained were recrystallized from ethyl acetate to provide 1.4 g of the title compound as colorless crystals. The structure and melting point of the compound obtained are shown in Table 1.
  • 19
  • aqueous sodium chloride [ No CAS ]
  • [ 1208-87-3 ]
  • [ 6317-59-5 ]
YieldReaction ConditionsOperation in experiment
In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; (3) The <strong>[1208-87-3]1-chloromethyl-4-phenylthiobenzene</strong> (3.0 g) is dissolved in N,N-dimemthylformamide (15 ml), and thereto is added finely divided sodium cyanide (1.0 g), and the mixture is stirred at room temperature for 17 hours. To the reaction mixture are added saturated aqueous sodium chloride solution (50 ml) and ice water (50 ml), and the mixture is extracted with ethyl acetate (100 ml*3). The combined extracts are washed with saturated aqueous sodium chloride solution (50 ml*3), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 1-cyanomethyl-4-phenylthiobenzene (2.9 g). NMR (CDCl3) delta: 7.29-7.38 (m, 9H), 3.71 (s, 2H)
  • 20
  • [ 1208-87-3 ]
  • [ 24155-42-8 ]
  • α-(2,4-dichlorophenyl)-β,N-imidazolylethyl 4-phenylthiobezyl ether nitrate [ No CAS ]
YieldReaction ConditionsOperation in experiment
85.1% 710 g of sodium hydroxide, 511.2 g of 1- (2,4-dichlorophenyl) -2-imidazole ethanol, 1136 ml of water, 5680 ml of toluene and 56.8 g of tetrabutylammonium bromide were placed in a room temperature (25 ° C.) 10L reaction flask, stirring was warmed to 58 ° C, a solution of <strong>[1208-87-3]4-phenylmercaptobenzyl chloride</strong> in toluene (554.1g ? 1130ml) was added dropwise over 1.5 hours. Reaction at 60 ° C 12hour,The layers were separated and the aqueous layer was discarded. The organic layer was washed with saturated aqueous sodium chloride solution three times (250 ml × 1 + 200 ml × 2), washed twice with water (200 ml × 2), dried over anhydrous magnesium sulfate, filtered and the filtrate was reduced in pressure , Temperature 55 ° C) was concentrated to dryness and toluene was recovered to obtain 1250.5 g of an oil. 5680 ml of a mixed solution (ethyl acetate: toluene = 1: 1) was added followed by 1136 ml of a 20percent nitric acid ethyl acetate solution and stirred at 25 ° C 3 hours, filtered, washed, the filter cake was collected, dried under atmospheric pressure at 40 ° C to give a light yellow solid 738g. Yield 71.4percent, HPLC pureDegree: 99.84percent.Into a 5000 ml reaction flask, 2800 ml of anhydrous ethanol, 340 ml of water, and 738 g of crude nitetazole were injected, and the temperature was raised to 60° C. to completely dissolve the solution. The solution was naturally cooled to 25° C., crystallized for 12 hours, filtered, and the filter cake was washed with a little ethyl acetate. , Drying under atmospheric pressure at 45°C gave 628 g of a white solid. Yield: 85.1percent, purity HPLC: 99.97percent.
82.1% In 1000ml of three necked flask equipped with a stirrer, thermometer, dropping funnel added 25.6g of 1-(2,4-dichlorophenyl)-2-imidazol-ethanol (0.1mol) , 120ml tetrahydrofuran, 40ml water, 6g (0. 15mol) of sodium hydroxide ,1.2g PEG-400 and slowly warmed to reflux. While stirring added drop wise 4-Phenylthio-benzylchloride 30g (0. 12 mol 95percent), completion of the addition in approximately 30min and stirring at constant temperature for 4h,then the reaction was cooled, added 400ml of Diethyl ether, separatedaqueous layer, then aqueous layer was extracted with diethyl ether (200ml X2), combined the organic layer, washed with water , dried over anhydrous sodiumsulfate, filtrate , at the room temperature in filtrate liquid slowy & dropwise added 10ml concentrated nitric acid, precipitate solid, suction filtered,washed with diethyl ether, recrystallized using 95percent of ethanol to obtain white solid 37.3g, yield 82.1percent. mp 136-138oC.
74.7% At room temperature (25 °C) Sodium hydroxide, 1- (2,4-dichlorophenyl) -2-imidazol ethanol, water, toluene, tetrabutylammonium bromide administered into the reaction flask, heated with stirring to 58 °C 4-phenyl benzyl benzyl chloride in toluene was added dropwise, and the addition was completed in 1.5 h. Insulation reaction 12h, layers were separated aqueous layer was discarded, and the organic layer was washed with a saturated aqueous sodium chloride solution, washed with water, the toluene layer was dried over anhydrous magnesium sulfate, filtered and the filtrate under reduced pressure (pressure of 1330 Pa, a temperature of 55 °C) and concentrated to dryness recovered toluene to give an oil, was added a mixed solvent (ethyl acetate: toluene = 1: 1), added 20percent nitric acid in ethyl acetate solution at room temperature (25 °C) was stirred for 3h crystallization, filtration, water washing, collecting The filter cake was dried under normal pressure at 40 °C to give a pale yellow solid
71.4% 710 g of sodium hydroxide, 511.2 g of 1-(2,4-dichlorophenyl)-2-imidazoleethanol, 1136 ml of water, 5680 ml of toluene and 56.8 of tetrabutylammonium bromide at room temperature (25 °C). g, put into a 10L reaction bottle, stir and heat to 58 °C,A toluene solution of 4-phenylhydrazinobenzyl chloride (554.1 g - 1130 ml) was added dropwise, and the dropwise addition was completed over 1.5 hours. The reaction was carried out at 60 °C for 12 hours, the layers were separated, the aqueous layer was discarded, and the organic layer was washed three times with a saturated aqueous solution of sodium chloride (250 ml X 1 + 200 ml Chi 2).The mixture was washed twice with water (200 ml X 2 ), dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated to dryness under reduced pressure (1330 Pa, temperature 55 °C) to yield toluene to give an oil of 1250.5 g. Toluene = 1:1) 5680ml, Further, and then 20percent of nitric acid was added 1136 ml of anethyl ester solution was stirred at 25 °C for 3 hours, filtered, washed with water, and the filter cake was collected and dried at 40 °C to give 738 g of pale yellow solid. The yield was 71.4percent, and the HPLC purity was 99.84percent.

 

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Technical Information

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