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Chemical Structure| 40360-44-9 Chemical Structure| 40360-44-9

Structure of 40360-44-9

Chemical Structure| 40360-44-9

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Product Details of [ 40360-44-9 ]

CAS No. :40360-44-9
Formula : C6H2Cl3NO2
M.W : 226.44
SMILES Code : O=C(O)C1=NC(Cl)=C(Cl)C=C1Cl
MDL No. :MFCD01086756
InChI Key :TVMKSGXYTVKNRK-UHFFFAOYSA-N
Pubchem ID :919593

Safety of [ 40360-44-9 ]

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

Computational Chemistry of [ 40360-44-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 46.23
TPSA ?

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

50.19 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.28
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

2.93
Log Po/w (WLOGP)?

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

2.74
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.

0.67
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

2.71
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.07

Water Solubility

Log S (ESOL):?

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

-3.39
Solubility 0.0914 mg/ml ; 0.000404 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.

-3.65
Solubility 0.0512 mg/ml ; 0.000226 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

-3.25
Solubility 0.126 mg/ml ; 0.000557 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.

-5.6 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.

0.56

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)

1.86

Application In Synthesis of [ 40360-44-9 ]

* 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.

  • Upstream synthesis route of [ 40360-44-9 ]

[ 40360-44-9 ] Synthesis Path-Upstream   1~9

  • 1
  • [ 32889-74-0 ]
  • [ 40360-44-9 ]
YieldReaction ConditionsOperation in experiment
68%
Stage #1: at 30℃;
Stage #2: With hydrogenchloride In water
To a reaction flask containing 200 mL of boiling water was added 26.1 g (0.1 mol) of tetrapicolinic acid, 4.1 g (0.103 mol) of sodium hydroxide previously dissolved in 25 mL of water and 3.47g (0.105mol) of anhydrous hydrazine. The reaction mixture was stirred under reflux for 30 min. An additional 4.1g (0.103mol) of sodium hydroxide in 25 mL of water was slowly added to <n="113"/>the reaction mixture over a 25 minute period and the mixture refluxed for 45 min. The reaction mixture was cooled to room temperature and 25 mL of 5N HCl was added. The solid 3,5,6- trichloro-4-hydrazinopicolinic acid (as the monohydrate) which precipitated was recovered by filtration in a yield of 22.9 g (83percent). Mp:166"-168°C. [00371] To a mixture (clear solution) of 3,5,6-tricWcro-4-hydrazinopicolinic acid (22.9 g, 78 mmol), 115 mL of2Qpercent sodium hydroxide and 15O mL of water was added 10O mL of 10-13percent sodium hypochlorite solution at 3O°C. Immediate gas evolution was noted which ceased after about 3 min. Five minutes after the addition of the sodium hypochlorite solution, the reaction mixture was acidified to a pH of about 2 with concentrated hydrochloric acid (15OmL). The mixture was extracted with methylene chloride. The methylene chloride was removed from the extract by evaporation leaving the crude 3,5,6-trichloropicolinic acid. The crude product was dissolved in IN NaOH to form a clear solution and cooled to 0 °C and neutralized with 5N HCl with stirring at O°C. The solid was filtered and washed with water to give the pure enough product (15.5 g, 88percent). Total yield: 68percent. Mp.l47-151°C. [00372] 1H NMR (DMSO^, 400 MHz): δ 14.31 (brs, 1H, OH, exchangeable with D2O), 8.60 (s, 1H).
References: [1] Patent: WO2009/89263, 2009, A2, . Location in patent: Page/Page column 111-112.
[2] Patent: US3971799, 1976, A, .
  • 2
  • [ 496849-77-5 ]
  • [ 40360-44-9 ]
YieldReaction ConditionsOperation in experiment
45.11% With [2,2]bipyridinyl; nickel(II) chloride hexahydrate; sodium hydroxide; zinc In N,N-dimethyl-formamide at 20℃; Inert atmosphere Three 8 mL scintillation vials were charged with NiC12•6H20 (12.0 mg, 0.05 1 mmol)and 2,2’-bipyridine (16.0 mg, 0.102 mmol). The vials were closed and purged with nitrogenfor 5 mm, after which the vials were charged with DMF (4.5 mL) and one of the following:deionized (DI) water (pH = 7), 10percent HC1, or 10percent sodium hydroxide (NaOH) (0.5 mL). The mixtures were allowed to stir for 5 mm. To each of the vials was added zinc dust (0.22 g, 3.4 mmol), and the mixtures were allowed to stir under nitrogen for 35 mm. Solid 3,4,5,6-tetrachloropicolinic acid (0.10 g, 0.4 mmol) was added to each through the top of the reactor. The reaction mixtures were allowed to stir at ambient temperature, and samples were removed periodically to determine reaction kinetics. The samples (—0.01 mL of reaction mixture diluted to 1.5 mL with acetonitrile) were analyzed by a calibrated HPLC method.
References: [1] Patent: WO2016/22623, 2016, A1, . Location in patent: Page/Page column 8; 9.
  • 3
  • [ 124-38-9 ]
  • [ 78121-76-3 ]
  • [ 40360-44-9 ]
References: [1] European Journal of Organic Chemistry, 2001, # 23, p. 4533 - 4536.
  • 4
  • [ 10469-09-7 ]
  • [ 496849-77-5 ]
  • [ 40360-44-9 ]
References: [1] Patent: WO2016/22623, 2016, A1, . Location in patent: Paragraph 6; 7.
  • 5
  • [ 16063-70-0 ]
  • [ 40360-44-9 ]
References: [1] European Journal of Organic Chemistry, 2001, # 23, p. 4533 - 4536.
  • 6
  • [ 406676-23-1 ]
  • [ 40360-44-9 ]
References: [1] European Journal of Organic Chemistry, 2001, # 23, p. 4533 - 4536.
  • 7
  • [ 10469-09-7 ]
  • [ 40360-44-9 ]
References: [1] Patent: WO2016/22623, 2016, A1, .
[2] Patent: US3971799, 1976, A, .
  • 8
  • [ 2402-79-1 ]
  • [ 40360-44-9 ]
References: [1] Patent: US2017/369412, 2017, A1, .
  • 9
  • [ 17824-83-8 ]
  • [ 40360-44-9 ]
References: [1] Patent: US3971799, 1976, A, .
 

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