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Chemical Structure| 39183-17-0 Chemical Structure| 39183-17-0

Structure of 39183-17-0

Chemical Structure| 39183-17-0

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Product Details of [ 39183-17-0 ]

CAS No. :39183-17-0
Formula : C6H5Cl2NO
M.W : 178.02
SMILES Code : OC1=CC=C(N)C(Cl)=C1Cl
MDL No. :MFCD14455913
InChI Key :OQHWFUQNSLMSBG-UHFFFAOYSA-N
Pubchem ID :9877529

Safety of [ 39183-17-0 ]

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

Computational Chemistry of [ 39183-17-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 2.0
Molar Refractivity 42.89
TPSA ?

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

46.25 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.57
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

2.7
Log Po/w (WLOGP)?

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

2.29
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.

2.02
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

1.94
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.1

Water Solubility

Log S (ESOL):?

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

-3.09
Solubility 0.145 mg/ml ; 0.000815 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.

-3.32
Solubility 0.0844 mg/ml ; 0.000474 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

-2.69
Solubility 0.361 mg/ml ; 0.00203 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.

-5.47 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

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

2.0 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)

1.4

Application In Synthesis of [ 39183-17-0 ]

* 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 [ 39183-17-0 ]

[ 39183-17-0 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 201656-71-5 ]
  • [ 39183-17-0 ]
YieldReaction ConditionsOperation in experiment
92% With sodium tetrahydroborate In ethanol at 20℃; for 4 h; Cooling with ice Equipped with a stirrer and a reflux condenser 100 ml two-necked flask, was added 8.0 g (0.03 mol) of starting material 2,3-dichloro-4-phenylazophenol, 1 g of sodium hydroxide dissolved in 40 ml ethanol, ice-water bath, sodium borohydride was added in small portions 4.5 g (0.12 mol). After completion of the dropwise addition, the ice bath was removed and the mixture was stirred, warmed to room temperature, the reaction was continued for 4 hours. After completion of the reaction, was added diluted hydrochloric acid solution to pH = 7, extracted three times with ethyl acetate, the combined organic phase was dried over anhydrous sodium sulfate, the solvent was distilled off rotary evaporator, was recrystallized from 20 ml of toluene, filtered and dried to give the product pale pink crystals 5.08 g, 95percent yield, 100percent pure.
139 kg With sodium dithionite; sodium hydroxide In ethanol; water at 40℃; for 4 h; Large scale Step 3, the azo obtained in step 2 is put into a reduction kettle. 500 kg of ethanol and 500 kg of water are added, and the temperature is raised to 40 ° C. First, 12.5 kg of sodium hydroxide is added to adjust the pH to 10, and then 50 kg of insurance powder is added ( Sodium dithionite, Na2O4S2). Repeatedly add 12.5kg of sodium hydroxide and 50kg of insurance powder 7 times. After the addition, the reaction is kept at this temperature for 4 hours. The azo is reduced by the action of the powder to form crude 2,3-dichloro-4-hydroxyaniline and aniline. Subsequently, the temperature was raised to 60 ° C and ethanol, water and reduced aniline were recovered under a vacuum of -0.087 MPa, and about 700 kg of the mixture was recovered after 4 hours of recovery. After the recovery, 800 kg of water was added to the crude 2,3-dichloro-4-hydroxyaniline, the temperature was raised to 60 ° C, the temperature was kept for 1 hour, the temperature was lowered to 30 ° C, and the mixture was centrifuged at 3,300 rpm for 10 minutes to obtain 180 to 200 kg of centrifugation. The material is removed by water washing to remove impurities such as water-soluble inorganic salts; the centrifugal material is recrystallized by using 99percent toluene to remove organic impurities, specifically: the centrifuge is put into the reaction vessel, 500 kg of toluene is added, and the temperature is raised to 84 ° C. The temperature was kept at this temperature for 1 hour, the temperature was lowered to 25 ° C, and the mixture was further centrifuged at 3,300 rpm for 10 minutes, and dried at 70 ° C for 3 hours to obtain 2,3-dichloro-4-hydroxyaniline. Among them, the weight of 2,3-dichloro-4-hydroxyaniline is 138-139 kg, the content is 98.0percent, the yield is 96percent, and the specific reduction of azo to 2,3-dichloro-4-hydroxyaniline The process is as shown in equation (3).
References: [1] Patent: CN105732403, 2016, A, . Location in patent: Paragraph 0038; 0039; 0040.
[2] Patent: CN108689875, 2018, A, . Location in patent: Paragraph 0053; 0059-0060; 0069; 0076.
  • 2
  • [ 111-48-8 ]
  • [ 576-24-9 ]
  • [ 39183-17-0 ]
YieldReaction ConditionsOperation in experiment
83% With hydrogenchloride; sodium hydroxide; hydrogen; aniline; sodium nitrite In methanol; water EXAMPLE 6
At 0 to 5° C., a solution of 3.8 g (0.055 mol) of NaNO2 in 6 ml of H2 O is added dropwise to 25 ml of aqueous HCl (15percent) and 4.9 g (0.0525 mol) of aniline in a 100 ml two-neck flask fitted with internal thermometer and magnetic stirrer.
After 10 minutes, this diazonium salt solution is added at 5 to 10° C. to a solution of 8.15 g (0.05 mol) of 2,3-dichlorophenol and 10 g (0.25 mol) of NaOH in 100 ml of H2 O.
The mixture is allowed to warm to room temperature, stirred for a further 1 hour and neutralized with aqueous HCl (pH=7).
In a 500 ml three-neck flask fitted with internal thermometer, stirrer and gas inlet tube, this solution is admixed with 300 ml of methanol, 2.5 g of Raney nickel and 15 μl of bis(2-hydroxyethyl) sulphide, and the flask is flushed with argon.
At 40 to 50° C., 2300 ml of hydrogen (0.1 mol) are then applied with a pressure of about 1 bar over 1.5 hours.
The reaction mixture is admixed with a little activated charcoal, stirred for a further 15 minutes and filtered over a bed of silica gel.
The methanol is distilled off and pure 4-hydroxy-2,3-dichloroaniline precipitates from the aqueous solution, giving a yield of 83percent.
References: [1] Patent: US6124504, 2000, A, .
  • 3
  • [ 576-24-9 ]
  • [ 39183-17-0 ]
References: [1] Patent: US6124504, 2000, A, .
[2] Patent: CN108689875, 2018, A, .
  • 4
  • [ 3209-22-1 ]
  • [ 39183-17-0 ]
References: [1] Patent: US5545754, 1996, A, .
[2] Patent: US5545754, 1996, A, .
 

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