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Chemical Structure| 131088-02-3 Chemical Structure| 131088-02-3

Structure of 131088-02-3

Chemical Structure| 131088-02-3

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Product Details of [ 131088-02-3 ]

CAS No. :131088-02-3
Formula : C7H5ClO3
M.W : 172.57
SMILES Code : O=CC1=CC(Cl)=C(O)C=C1O
MDL No. :MFCD18324145
Boiling Point : No data available
InChI Key :IPOSHVWRFQTHGK-UHFFFAOYSA-N
Pubchem ID :14766072

Safety of [ 131088-02-3 ]

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

Computational Chemistry of [ 131088-02-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 40.89
TPSA ?

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

57.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.13
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

1.85
Log Po/w (WLOGP)?

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

1.56
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.

0.78
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

1.67
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.4

Water Solubility

Log S (ESOL):?

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

-2.41
Solubility 0.667 mg/ml ; 0.00386 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 0.361 mg/ml ; 0.00209 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

-1.81
Solubility 2.69 mg/ml ; 0.0156 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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.04 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)

1.29

Application In Synthesis of [ 131088-02-3 ]

* 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 [ 131088-02-3 ]

[ 131088-02-3 ] Synthesis Path-Downstream   1~2

  • 1
  • (2,4-dichloro-3-iodophenyl)methanol [ No CAS ]
  • [ 131088-02-3 ]
  • [ 135124-71-9 ]
  • 5-((4-chloro-5-((2,4-dichloro-3-iodobenzyl)oxy)-2-formylphenoxy)methyl)nicotinonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
32% Intermediate: 5-((4-chloro-5-((2,4-dichloro-3-iodobenzyl)oxy)-2-formylphenoxy)methyl)nicotinonitrile To a dry vial under N2 was added (2,4-dichloro-3-iodophenyl)methanol (150 mg, 0.495 mmol), 5-chloro-2,4-dihydroxybenzaldehyde (85 mg, 0.495 mmol), triphenylphosphine (136 mg, 0.519 mmol) and THF (2.5 mL). The reaction was flushed with argon, treated with DIAD (100 muL, 0.514 mmol), capped and stirred at room temp for 1 h. The reaction was charged with additional PPh3 (27 mg, 0.103 mmol) and DIAD (20 mulit, 0.103 mmol), flushed with argon, capped, and stirred at room temp for 18 h. The reaction was then treated with triphenylphosphine (170 mg, 0.648 mmol), <strong>[135124-71-9]5-(hydroxymethyl)nicotinitrile</strong> (83 mg, 0.619 mmol), TMAD (107.3 mg, 0.617 mmol), THF (4.5 mL). The mixture was flushed with N2, capped and heated at 65 C. in an oil bath for 2 h, followed by room temp for 18 h. The reaction was filtered and the filtrate was evaporated to dryness in vacuo. The residue was applied to the head of a 40 g Teledyne Isco Silica Flash Column, and the column was eluted with a linear gradient from 100% Hexanes to 100% EtOAc over 15 column volumes. The fractions containing the desired product were pooled and evaporated to dryness to give the title compound (91.5 mg, 32%). 1H NMR (500 MHz, CHLOROFORM-d) delta 10.31 (s, 1H), 8.93 (br d, J=6.4 Hz, 2H), 8.10 (s, 1H), 7.97 (s, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.49 (d, J=8.4 Hz, 1H), 6.55 (s, 1H), 5.31 (s, 2H), 5.25 (s, 2H).
  • 2
  • [ 131088-02-3 ]
  • [ 76350-90-8 ]
  • 5-chloro-2-hydroxy-4-((2-methyl-[1,1'-biphenyl]-3-yl)methoxy)benzaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
5.5 g 4g 5-chloro-2,4-dihydroxybenzaldehyde and 5g<strong>[76350-90-8]2-methyl-3-phenylbenzyl alcohol</strong>,8.2 g of triphenylphosphine (PPh3)Add to 50 ml of anhydrous tetrahydrofuran,Stir for 15 minutes,8.2 mL of diisopropyl azodicarboxylate (DIAD) was added dropwise in small portions to the reaction solution for 10 hours.Thin layer chromatography (TLC) monitoring,After the reaction was completed, the reaction solution was poured into 100 mL of water.Extracted with ethyl acetate (100 mL × 5), and allowed to stand for separation.The organic phase was treated with 5% sodium hydrogencarbonate (NaHCO3) (80 mL×3),Wash with saturated brine (80 mL × 3), then dry over anhydrous magnesium sulfate.Filter with suction and remove ethyl acetate under reduced pressure.After column chromatography V (petroleum ether): V (ethyl acetate) = 10:15-Chloro-2-hydroxy-4-((2-methyl-[1,1'-biphenyl]-3-yl)methoxy)benzaldehyde 5.5 g was obtained.
 

Historical Records

Technical Information

• Acidity of Phenols • Alkyl Halide Occurrence • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Chan-Lam Coupling Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Chaykovsky Reaction • Corey-Fuchs Reaction • Electrophilic Substitution of the Phenol Aromatic Ring • Etherification Reaction of Phenolic Hydroxyl Group • Fischer Indole Synthesis • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Halogenation of Phenols • Hantzsch Dihydropyridine Synthesis • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Julia-Kocienski Olefination • Kinetics of Alkyl Halides • Knoevenagel Condensation • Kumada Cross-Coupling Reaction • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Mukaiyama Aldol Reaction • Nozaki-Hiyama-Kishi Reaction • Oxidation of Phenols • Passerini Reaction • Paternò-Büchi Reaction • Pechmann Coumarin Synthesis • Petasis Reaction • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reformatsky Reaction • Reimer-Tiemann Reaction • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Stetter Reaction • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

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