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Chemical Structure| 3964-54-3 Chemical Structure| 3964-54-3

Structure of 3964-54-3

Chemical Structure| 3964-54-3

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Product Citations

Product Citations

Uppu, Rao M ; Fronczek, Frank R ;

Abstract: In the title compound, C8H8ClNO2, the acetamide substituent is twisted out of the phenyl plane, forming a dihedral angle of 58.61 (7)°. In the extended structure, each molecule donates two hydrogen bonds [N—H···O(carbonyl) and O—H···O(carbonyl)] and thus also accepts two such hydrogen bonds. The chlorine atom is not involved in the hydrogen bonding.

Keywords: crystal structure ; acetamino­phen ; acetamino­phen impurity C ; cellular oxidants ; non-enzymatic biotransformation

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Product Details of [ 3964-54-3 ]

CAS No. :3964-54-3
Formula : C8H8ClNO2
M.W : 185.61
SMILES Code : C1=C(C=CC(=C1Cl)O)NC(C)=O
English Name :N-(3-Chloro-4-hydroxyphenyl)acetamide
MDL No. :MFCD01318123
InChI Key :JULKJDRBSRRBHT-UHFFFAOYSA-N
Pubchem ID :77579

Safety of [ 3964-54-3 ]

Computational Chemistry of [ 3964-54-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 47.79
TPSA ?

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

49.33 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.62
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

2.02
Log Po/w (WLOGP)?

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

1.81
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.

1.5
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

1.53
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.7

Water Solubility

Log S (ESOL):?

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

-2.5
Solubility 0.585 mg/ml ; 0.00315 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.

-2.68
Solubility 0.385 mg/ml ; 0.00207 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

-2.83
Solubility 0.276 mg/ml ; 0.00149 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.

-6.0 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

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)

1.22

Application In Synthesis of [ 3964-54-3 ]

* 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 [ 3964-54-3 ]

[ 3964-54-3 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 619-08-9 ]
  • [ 3964-54-3 ]
YieldReaction ConditionsOperation in experiment
With acetic anhydride; acetic acid; platinum Hydrogenation;
  • 2
  • [ 3964-52-1 ]
  • [ 64-19-7 ]
  • [ 3964-54-3 ]
  • 3
  • [ 50-00-0 ]
  • [ 3964-54-3 ]
  • [ 109-89-7 ]
  • [ 855350-48-0 ]
YieldReaction ConditionsOperation in experiment
With ethanol Erhitzen des Reaktionsprodukts mit wss. HCl, anschliessend mit 4,7-Dichlor-chinolin;
  • 4
  • [ 3964-54-3 ]
  • [ 100-35-6 ]
  • [ 110179-58-3 ]
YieldReaction ConditionsOperation in experiment
With sodium ethanolate
  • 5
  • [ 3964-54-3 ]
  • [ 20098-48-0 ]
  • [ 60963-13-5 ]
YieldReaction ConditionsOperation in experiment
(i) KOtBu, DMSO, (ii) /BRN= 2505480/, DMF; Multistep reaction;
  • 6
  • [ 50700-49-7 ]
  • [ 103-90-2 ]
  • [ 3964-54-3 ]
  • [ 106-51-4 ]
YieldReaction ConditionsOperation in experiment
1: 65% 2: 10% 3: 17% With potassium chloride; potassium acetate; acetic acid In water at 25℃; other buffers; effect of pH (3.09 - 7.77);
With hydrogenchloride; dipotassium hydrogenphosphate; potassium dihydrogenphosphate In water; acetonitrile at 40℃;
  • 7
  • [ 50700-49-7 ]
  • [ 3964-54-3 ]
  • [ 106-51-4 ]
YieldReaction ConditionsOperation in experiment
In water; acetonitrile at 25℃; hydrolysis in HCl solutions with various buffers, KCl or KCl-KClO3, pH range 0.3-10.5;
  • 8
  • [ 99512-61-5 ]
  • [ 103-90-2 ]
  • [ 3964-54-3 ]
  • [ 50700-49-7 ]
  • [ 51-66-1 ]
  • [ 106-51-4 ]
YieldReaction ConditionsOperation in experiment
With dipotassium hydrogenphosphate; potassium dihydrogenphosphate; potassium chloride In water at 25℃; various buffers; effect of pH (3.09 - 7.82);
  • 9
  • [ 102725-57-5 ]
  • [ 62-44-2 ]
  • [ 103-90-2 ]
  • [ 3964-54-3 ]
  • [ 106-51-4 ]
YieldReaction ConditionsOperation in experiment
1: 14 % Chromat. 2: 44 % Chromat. 3: 8 % Chromat. 4: 1.3 % Chromat. With dipotassium hydrogenphosphate; potassium dihydrogenphosphate; water In acetonitrile at 25℃; also N-acetyl-p-benzoquinone imine, var. buffer, var. pH; mechanism;
  • 10
  • [ 91631-54-8 ]
  • [ 103-90-2 ]
  • [ 3964-54-3 ]
  • [ 16323-09-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
1: 3.7 % Chromat. 2: 4.9 % Chromat. 3: 41 % Chromat. 4: 8.0 % Chromat. With potassium chloride In water; acetonitrile at 40℃; Further byproducts given;
  • 11
  • [ 91631-54-8 ]
  • [ 6975-29-7 ]
  • [ 103-90-2 ]
  • [ 3964-54-3 ]
  • [ 16323-09-4 ]
  • [ CAS Unavailable ]
  • [ 106-51-4 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; potassium chloride In water; acetonitrile at 30 - 80℃; activation parameters(ΔH++, ΔS++); further reaction conditions;
1: 3.7 % Chromat. 2: 4.9 % Chromat. 3: 41 % Chromat. 4: 20 % Chromat. 5: 8.0 % Chromat. 6: 18 % Chromat. With hydrogenchloride; potassium chloride In water; acetonitrile at 40℃; further reaction conditions;
  • 12
  • [ 91631-54-8 ]
  • [ 6975-29-7 ]
  • [ 103-90-2 ]
  • [ 3964-54-3 ]
  • [ 16323-09-4 ]
  • [ 96648-97-4 ]
  • [ 106-51-4 ]
YieldReaction ConditionsOperation in experiment
1: 3.7 % Chromat. 2: 4.9 % Chromat. 3: 41 % Chromat. 4: 20 % Chromat. 5: 8.0 % Chromat. 6: 18 % Chromat. With potassium chloride In water; acetonitrile at 40℃; various potassium halides;
  • 13
  • [ 110-87-2 ]
  • [ 3964-54-3 ]
  • [ 220587-30-4 ]
YieldReaction ConditionsOperation in experiment
84% With pyridinium p-toluenesulfonate In dichloromethane; ethyl acetate for 48h; Ambient temperature;
  • 14
  • [ 7073-42-9 ]
  • [ 3964-54-3 ]
YieldReaction ConditionsOperation in experiment
With aluminium trichloride; phenylmethanethiol In dichloromethane 1) 0 deg C, 2) r.t., 3 h; Yield given;
 

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