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Chemical Structure| 3218-49-3 Chemical Structure| 3218-49-3
Chemical Structure| 3218-49-3

3,4-Dichlorophenylacetonitrile

CAS No.: 3218-49-3

4.5 *For Research Use Only !

Cat. No.: A336923 Purity: 99%

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Product Details of [ 3218-49-3 ]

CAS No. :3218-49-3
Formula : C8H5Cl2N
M.W : 186.04
SMILES Code : C1=C(C=CC(=C1Cl)Cl)CC#N
MDL No. :MFCD00001909
Boiling Point : No data available
InChI Key :QWZNCAFWRZZJMA-UHFFFAOYSA-N
Pubchem ID :76690

Safety of [ 3218-49-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352+P312-P304+P340+P312-P305+P351+P338

Calculated chemistry of [ 3218-49-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 45.98
TPSA ?

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

23.79 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.94
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

3.28
Log Po/w (WLOGP)?

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

3.06
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.

2.94
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

3.4
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.92

Water Solubility

Log S (ESOL):?

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

-3.4
Solubility 0.0745 mg/ml ; 0.0004 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.

-3.45
Solubility 0.0653 mg/ml ; 0.000351 mol/l
Class?

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

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

-4.12
Solubility 0.0141 mg/ml ; 0.0000757 mol/l
Class?

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

Moderately 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.

-5.11 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)

1.35

Application In Synthesis of [ 3218-49-3 ]

* 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 [ 3218-49-3 ]

[ 3218-49-3 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 1120-95-2 ]
  • [ 3218-49-3 ]
  • [ 81102-53-6 ]
  • 2
  • [ 60-29-7 ]
  • [ 25150-61-2 ]
  • [ 3218-49-3 ]
  • α-(3,4-Dichlorophenyl)-1-pyrrolidinepropanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; sodium hydroxide; paraformaldehyde; In ethanol; Preparation 11 α-(3,4-Dichlorophenyl)-1-pyrrolidinepropanenitrile To 100 mL of ethanol is added (18.6 g (0.1 mol) 3,4-dichlorobenzeneacetonitrile, 12.6 g (0.12 mol) of <strong>[25150-61-2]pyrrolidine hydrochloride</strong>, 6.0 g (0.2 mol) of paraformaldehyde and 1 mL of concentrated hydrochloric acid. Stir the mixture at reflux. Monitor the progress of the reaction by thin-layer chromatography. Upon completion add 300 mL of 1N HCl and extract with 200 mL of Et2 O. Add 4N NaOH to the aqueous solution until basic and extract the aqueous solution with two 100 mL portions of CH2 Cl2. Dry the organic phase over anhydrous Na2 SO4. Filter the drying agent and evaporate the solvent in vacuo to obtain the title compound.
  • 3
  • [ 54221-96-4 ]
  • [ 3218-49-3 ]
  • C15H12Cl2N2O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
2-(3,4-dichlorophenyl)acetonitrile (3.50 g, 18.8 mmol) was taken up in THF (30 mL) and diethyl ether (30 mL), and cooled to -78 °C in an acetone-dry ice bath. BuLi (8.1 mL, 20 mmol, 1.6 M in hexane) was added drop-wise, and the temperature was maintained below -60 °C. Once the last drop had been added, the reaction was allowed to stir for 15 minutes. This solution became orange clear. 6- methoxypicolinaldehyde (2.3 mL, 19 mmol) dissolved in THF (20 mL) was added slowly drop-wise, and the temperature was maintained below -60 °C. Solution was dark brown / black clear at this point and was allowed to stir for 1.5 hours at -75 °C. The reaction was quenched with acetic acid (1.6 mL, 28 mmol) dissolved in 5 mL of diethyl ether, added drop-wise while the reaction was cooled in the dry ice acetone bath. The temperature was maintained below -60 °C. LCMS revealed mostly one peak with the desired mass. The reaction was worked up by adding 100 mL of water, and layers were separated. The aqueous phase was extracted with ethyl acetate three times. The combined organic layers were washed with brine, dried over MgSC , and concentrated in vacuo to afford 8.14 grams of a clear amber oil. LCMS revealed a peak that was consistent with desired material. The material was absorbed onto silica gel and ran through an ISCO 80 gram column, eluting with CH2C12 / EtOAc. The broad peak looked to be a mixture of diastereomers in a ratio around 1.5:1. It was not determined which diastereomeric pair is the more predominant pair (0.988 g). The spiked shoulder from that broad peak looked to be a mixture of diastereomers in a ratio around 4: 1 (4.39 g).
 

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