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Chemical Structure| 1878-65-5 Chemical Structure| 1878-65-5

Structure of 1878-65-5

Chemical Structure| 1878-65-5

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Product Details of [ 1878-65-5 ]

CAS No. :1878-65-5
Formula : C8H7ClO2
M.W : 170.59
SMILES Code : C1=C(C=CC=C1Cl)CC(O)=O
MDL No. :MFCD00004332
InChI Key :WFPMUFXQDKMVCO-UHFFFAOYSA-N
Pubchem ID :15879

Safety of [ 1878-65-5 ]

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

Computational Chemistry of [ 1878-65-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 43.0
TPSA ?

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

37.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.54
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

2.09
Log Po/w (WLOGP)?

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

1.97
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.

2.25
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

2.18
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.0

Water Solubility

Log S (ESOL):?

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

-2.49
Solubility 0.557 mg/ml ; 0.00327 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.

-2.5
Solubility 0.535 mg/ml ; 0.00314 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

-2.79
Solubility 0.279 mg/ml ; 0.00164 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.

-5.86 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.

0.56

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

0.0 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)

1.21

Application In Synthesis of [ 1878-65-5 ]

* 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 [ 1878-65-5 ]

[ 1878-65-5 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 1878-65-5 ]
  • [ 14062-29-4 ]
YieldReaction ConditionsOperation in experiment
86.8% sulfuric acid; In ethanol; EXAMPLE 6 2-(3-Chloro-phenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamide (3-Chloro-phenyl)-acetic acid (6.03 g, 0.03 mol) was dissolved in ethanol (37.7 mL) and treated with a catalytic amount of sulfuric acid. The reaction mixture was refluxed for 12 h. The reaction was concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 50/50 hexanes/ethyl acetate) afforded (3-chloro-phenyl)-acetic acid ethyl ester (6.10 g, 86.8%) as a clear oil: EI-HRMS m/e calcd for C10H11ClO2 (M+) 198.0448, found 198.0442.
86.8% sulfuric acid; In ethanol; EXAMPLE 6 2-(3-Chloro-phenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamide (3-Chloro-phenyl)-acetic acid (6.03 g, 0.03 mol) was dissolved in ethanol (37.7 mL) and treated with a catalytic amount of sulfuric acid. The reaction mixture was heated under reflux for 12 h. The reaction was concentrated in. vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 50/50 hexanes/ethyl acetate) afforded (3-chloro-phenyl)-acetic acid ethyl ester (6.10 g, 86.8%) as a clear oil: EI-HRMS m/e calcd for C10H11ClO2 (M+) 198.0448, found 198.0442.
  • 4
  • [ 2632-65-7 ]
  • [ 1878-65-5 ]
  • [ 1392494-19-7 ]
  • 5
  • [ 14062-29-4 ]
  • [ 1878-65-5 ]
YieldReaction ConditionsOperation in experiment
91% With water; sodium hydroxide; In 1,4-dioxane; at 60℃; for 2h;pH 10 - 14; m-Chlorotoluene (1.89 g), ethanol (46 mg), di-tert-butyl peroxide (73 mg, 1 equivalent), and Pd(Xantphos)Cl2 (3.8 mg, 1 mol %) were added into a reaction kettle, into which 10 atm carbon monoxide was introduced. The reaction was heated to 120 C., and stirred at this constant temperature for 16 h. After the reaction was completed, carbon monoxide was discharged, and 82 mg ethyl m-chlorophenylacetate was obtained by column chromatography, in a yield of 83%. 1HNMR (400 MHz, CDCl3) delta 1.24 (t, J=7.2 Hz, 3H), 3.58 (s, 2H), 4.13 (q, J=7.2 Hz, 2H), 7.15-7.18 (m, 1H), 7.24-7.26 (m, 1H), 7.29 (s, 1H); 13CNMR (100 MHz, CDCl3) delta 14.2, 40.9, 61.1, 127.3, 127.5, 129.5, 129.8, 134.3, 135.9, 170.9; HRMS (ESI) calcd. for C10H11ClNaO2 [M+Na]: 221.0340. found: 221.0342. The ethyl m-chlorophenylacetate obtained was dissolved in 1,4-dioxane. 6 N sodium hydroxide solution was added, and the reaction was heated to 60 C. After 2 h of reaction, the pH value was adjusted to 1 by adding 2 N hydrochloric acid. After removing the organic solvent under reduced pressure, 64 mg product m-chlorophenylacetic acid was obtained by extraction with ethyl acetate, and the yield of hydrolysis was 91%.
 

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