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Structure of 68817-71-0

Chemical Structure| 68817-71-0

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Product Details of [ 68817-71-0 ]

CAS No. :68817-71-0
Formula : C12H11ClN2
M.W : 218.68
SMILES Code : NC1=CC=CC=C1NC2=CC=C(Cl)C=C2
MDL No. :MFCD00007686
InChI Key :WEUBIWJPIRTWDF-UHFFFAOYSA-N
Pubchem ID :522323

Safety of [ 68817-71-0 ]

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

Computational Chemistry of [ 68817-71-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 0.0
Num. H-bond donors 2.0
Molar Refractivity 65.4
TPSA ?

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

38.05 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.06
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

3.41
Log Po/w (WLOGP)?

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

3.67
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.

3.22
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

2.62
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.0

Water Solubility

Log S (ESOL):?

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

-3.8
Solubility 0.0343 mg/ml ; 0.000157 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.

-3.89
Solubility 0.0282 mg/ml ; 0.000129 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

-5.23
Solubility 0.00129 mg/ml ; 0.00000589 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

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.

-5.21 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.

0.55

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)

2.1

Application In Synthesis of [ 68817-71-0 ]

* 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.

  • Downstream synthetic route of [ 68817-71-0 ]

[ 68817-71-0 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 23008-56-2 ]
  • [ 68817-71-0 ]
YieldReaction ConditionsOperation in experiment
93.2% With iron; ammonium chloride; In ethanol; water; at 70℃; for 2h; N2-(4-chloro henyl)benzene-l,2-diamineTo a mixture of EtOH (100 ml) and NH4C1 saturated solution (15 ml),<strong>[23008-56-2]N-(4-chlorophenyl)-2-nitrobenzenamine</strong> (5.0 g, 20.1 mmol) was added, followed by iron powder (4.0 g). The reaction mixture was heated at 70 °C for 2h. The solid was filtered and the filtrate was extracted by EA (100 mL x 3), dried over Na2S04. After the solvent was removed, the mixture was purified by Combi-flash (PE : EA = 5 : 1) to giveN1-(4-chlorophenyl)benzene-l,2-diamine (4.1 g, 93.2 percent) as a light yellow solid. LRMS (M + H+) m/z calcd 218.06; found 218. 1H NMR (300 MHz, CD3OD): delta 6.52-6.59 (m, 3H), 6.70-6.74 (m, 1H), 6.81-6.87 (m, 1H), 6.90-6.99 (m, 3H).
92% With hydrogen; nickel; In N,N-dimethyl-formamide; at 60 - 70℃; In the hydrogenation reactor,100 g of N- (4-chlorophenyl) -2-nitro-1-aniline and 200 g of DMF were charged,After nitrogen replacement,Put 10 grams of nickel metal catalyst.Turn on stirringWarming to 60 degrees,Hydrogen gas to 3 kg pressure.Continuous access to hydrogen at 60 to 70 degrees,Until it no longer absorbs hydrogen,HPLC-controlled reaction process.When the condensate intermediate disappears,The reaction reached the end.Nitrogen replacement reaction system,Nickel catalyst was removed by hot filtration.The resulting filtrate was concentrated under reduced pressure to give about 100 g of DMF,Add 200 grams of deionized water,After slowly cooling to 20 degrees crystallization.The solid was isolated by filtration,After the solid was washed with appropriate amount of deionized water,Then cold toluene washing, drying.Finally, 81 g of crude N- (4-chlorophenyl) -1,2-phenylenediamine was obtained,Yield 92percentPurity greater than 98percentColor is gray brown.
With acetic acid; zinc; In dichloromethane; To a solution of 2-(4-chloroanilino)- nitrobenzene (57.0 g) in CH2C12 (40 mL) was added AcOH (90 mL), then Zn (105 g) was added in small potions. After Zn was added, the color of the mixture became light green, filtered by suction, washed with CH2C12. The filtrate was concentrated to dryness. Water was added, filtered, and washed with water to give a brown solid. This solid was used directly in the next step without further purification
With hydrogenchloride; iron; In water; at 90℃; General procedure: To a slurry containing iron powder (94.5 mmol) and distilled water(20 mL), the crude 2-nitro-N-phenylanilinewas added at room temperature. Upon dropwise addition of concentratedhydrochloric acid (0.3 mL), the mixture was stirred at 90 C for 1-2 hours.Reaction completion was confirmed via TLC and the mixture was cooled to roomtemperature. The mixture was extracted with ether (5 x 20 mL) and the organicphase was evaporated in vacuo toobtain intermediates 4a-j.3
With iron; acetic acid; In water; ethyl acetate; for 6h;Reflux; General procedure: A mixture of N-substituted-2-nitroanilines (50 mmol), ironpowder (250 mmol), acetic acid (500 mmol), water (35 ml) andethyl acetate (80 ml) was heated to reflux for 6 h. After completionof the reaction as indicated by TLC, the mixture was filtered immediately.The organic layer of the filtrate was separated, washedwith water, dried over anhydrous Na2SO4 and concentrated underreduced pressure to obtain diamines (16a?16n) as a brown solid.
With iron; ammonium chloride; In ethanol; water; at 90℃; for 3h; General procedure: The main procedure is shown in Scheme 2. The raw products of compound 7 were synthesized via one-pot method in a flask containing compounds 5 (30 mmol), 6 (30 mmol), K2CO3 (15 mmol) and PEG1000 (0.45 mmol). The reactions were carried out under stirring at 185 °C and were monitored by TLC. After reactions completion, the desired diphenylamine derivatives 7 were obtained via column chromatographic purification. Next, compounds 7 (20 mmol), reductive iron powder (60 mmol), solid NH4Cl (60 mmol) and ethanol aqueous solution (75percent, 50 mL) were added. The reactions proceeded with refluxing for 3 h at 90 °C and compounds 8 were obtained. Then, compound 3 (30 mmol) and SOCl2 (thionylchloride, 30 mL) were added. The mixture was heated to reflux at 90 °C for 3 h. Residual SOCl2 was removed by vacuum distillation in order to obtain compound 4. Finally, the primary amines 8 (10 mmol) dissolved in dichloromethane (CH2Cl2, 5 mL) and triethylamine(Et3N, 10 mL) were added. The mixture was cooled to 0 °C and compound 4 (20 mmol) dissolved in dichloromethane (CH2Cl2, 10 mL) was added dropwise under stirring at a temperature not exceeding 5 °C. The final mixture was stirred at room temperature for 10 h and the target compounds 9a, 9b and 9c were purified via column chromatography and recrystallization.

  • 2
  • [ 5555-00-0 ]
  • [ 68817-71-0 ]
  • N-(2-((4-chlorophenyl)amino)phenyl)-2-methylfuran-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at 20℃; for 2h; General procedure: To a solution of compounds 4a-j (0.02 mol) in triethylamine (5 mL) and dichloromethane (15 mL)in an ice bath, freshly prepared 3-furoyl chloride was added dropwise and theresulting mixture was stirred at room temperature for 2 hours. The mixture wasthen filtered, successively washed with aqueous sodium hydroxide (5%, 3 x 15mL) and water (2 x 15 mL). The organic phase wasthen dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to remove dichloromethane.Finally, the residue was purified by column chromatography to yield the finaltarget compounds 5a-j.4 2-methyl-N-(2-(phenylamino)phenyl)furan-3-carboxamide(5a).Yield, 62.8 %; white solid; mp, 133.8-134.6 ; 1HNMR (400 MHz, DMSO) delta 9.25 (s, 1H), 7.60 - 7.52 (m, 2H), 7.44 (s, 1H), 7.30 (dd, J =8.1, 1.1 Hz, 1H), 7.20 (d, J = 7.5 Hz, 1H), 7.19 - 7.12 (m, 2H), 7.04 -6.97 (m, 1H), 6.91 (s, 1H), 6.89 (s, 1H), 6.87 (d, J = 1.7 Hz, 1H), 6.79(t, J = 7.3 Hz, 1H), 2.53 (d, J = 3.3 Hz, 3H). 13C NMR(400 MHz, DMSO): delta 161.70, 156.40, 143.87, 140.53, 136.28, 128.89, 125.75, 125.54, 121.53,120.01, 119.19, 116.05, 109.23, 13.05. ESI MS: m / z 314.98 [M + Na]+.
 

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