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Chemical Structure| 106651-81-4 Chemical Structure| 106651-81-4

Structure of 106651-81-4

Chemical Structure| 106651-81-4

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Product Details of [ 106651-81-4 ]

CAS No. :106651-81-4
Formula : C7H9Cl2N
M.W : 178.06
SMILES Code : CC1=NC=C(CCl)C=C1.[H]Cl
MDL No. :MFCD11111128
InChI Key :GVMVLNGLIOYALD-UHFFFAOYSA-N
Pubchem ID :12214339

Safety of [ 106651-81-4 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H314
Precautionary Statements:P260-P264-P270-P280-P301+P312-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P321-P330-P363-P405-P501
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 106651-81-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.29
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 45.93
TPSA ?

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

12.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

2.44
Log Po/w (WLOGP)?

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

2.78
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.

1.8
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

2.77
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.96

Water Solubility

Log S (ESOL):?

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

-2.86
Solubility 0.246 mg/ml ; 0.00138 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.

-2.35
Solubility 0.788 mg/ml ; 0.00443 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

-3.41
Solubility 0.0698 mg/ml ; 0.000392 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

No
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.

-5.65 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

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<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)

1.39

Application In Synthesis of [ 106651-81-4 ]

* 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 [ 106651-81-4 ]

[ 106651-81-4 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 34107-46-5 ]
  • [ 106651-81-4 ]
YieldReaction ConditionsOperation in experiment
96% With thionyl chloride; In chloroform; toluene; at 20 - 35℃; for 1h; A solution of this alcohol compound (52.2 g, 424 mmol) in 190 ml toluene and 60 ml CHCl3 was added dropwise to a solution of SOCl2 (34 ml, 469 mmol) in 44 ml toluene, all the while maintaining the internal temperature between 23 and 35. After the end of the addition the reaction mixture was vigorously stirred at room temperature for 1 h and water pump vacuum was applied until the solvent was completely evaporated. The brown precipitate was resuspended in toluene, rapidly filtered off and washed three times with toluene. Drying in the desiccator (aspirator vacuum) gave 72.1 g (405 mmol, 96%) of 5-(chloromethyl)-2-methylpyridine hydrochloride as a brown solid.
92% With thionyl chloride; In toluene; at 65℃; for 1h; Step B: Preparation of 5-(chloromethyl)-2-methylpyridine hydrochloride: (6-Methylpyridin-3-yl)methanol (8.54 g, 69.34 mmol) was dissolved in toluene (0.5M, 125 mL). Thionyl chloride (10.12 mL, 138.7 mmol) was added dropwise, during which a white solid began to precipitate out of solution. The mixture was heated to 65 C and stirred for 1 hour. The mixture was concentrated, shaken in ether and collected by filtration to provide 5- (chloromethyl)-2-methylpyridine hydrochloride (11.3 g, 92% yield) as a beige solid.
With thionyl chloride; In dichloromethane; at 23℃; Method XLXV: Compound FG: Starting with (2-methylpyridine-5-yl)-methanol (5.07 g) in CH2Cl2 (50.0 mL), 4 equivs of SOCl2 (12.0 mL) were added at 23 C. The mixture was allowed to stir overnight and was then concentrated in vacuo, giving Compound FG as a monohydrochloride salt, which was used without purification. 1H NMR: (DMSO-d6, 300 MHz): delta 8.84 (s, 1H), 8.44 (d, J=6.9 Hz, 1H), 7.86 (d, J=7.8 Hz, 1H), 4.92 (s, 2H), 2.1 (s, 3H).
1.64 g With thionyl chloride; In tetrahydrofuran; at 35℃;Cooling with ice; A) 5- (chloromethyl) -2-methylpyridine hydrochloride To a solution of ( 6-methylpyridin-3-yl ) methanol . (1.24 g) in THF (12.4 mL) was added thionyl chloride (1.10 mL) under ice-cooling, and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and the obtained residue was suspended in ethyl acetate. The precipitate was collected by filtration, and washed with ethyl acetate-hexane to give, the title compound (1.64 g) . NMR (300 MHz, DMSO-d6) delta 2.72 (3H, s) , 4.93 (2H, s) , 7.86 (1H, d, J = 8.1 Hz), 8.44 (1H, dd, J = 8.2, 2.0 Hz), 8.85 (1H, d, J = 1. 9 Hz).

 

Historical Records

Technical Information

Categories

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[ 106651-81-4 ]

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