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Chemical Structure| 40434-87-5 Chemical Structure| 40434-87-5

Structure of 40434-87-5

Chemical Structure| 40434-87-5

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Product Details of [ 40434-87-5 ]

CAS No. :40434-87-5
Formula : C15H16O4S
M.W : 292.35
SMILES Code : O=S(C1=CC=C(C)C=C1)(OC[C@H](O)C2=CC=CC=C2)=O
MDL No. :MFCD00236055
InChI Key :IOTJIFRGXYQHAQ-HNNXBMFYSA-N
Pubchem ID :1726483

Safety of [ 40434-87-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 40434-87-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 20
Num. arom. heavy atoms 12
Fraction Csp3 0.2
Num. rotatable bonds 5
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 76.04
TPSA ?

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

71.98 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.14
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

2.42
Log Po/w (WLOGP)?

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

3.19
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.

2.67
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

2.27
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.54

Water Solubility

Log S (ESOL):?

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

-3.29
Solubility 0.15 mg/ml ; 0.000511 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.

-3.57
Solubility 0.078 mg/ml ; 0.000267 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

-4.84
Solubility 0.00425 mg/ml ; 0.0000145 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

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.

-6.37 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<0.0
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)

3.43

Application In Synthesis of [ 40434-87-5 ]

* 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 [ 40434-87-5 ]

[ 40434-87-5 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 16355-00-3 ]
  • [ 98-59-9 ]
  • [ 40434-87-5 ]
YieldReaction ConditionsOperation in experiment
78% With pyridine; at 0 - 20℃;Inert atmosphere; To a stirred solution of (i?)-l-phenylethane-l ,2-diol (0.5 g, 3.6 mmol, 1.0 eq.) in anhydrous pyridine (2 mL) under a nitrogen atmosphere at 0 C was added 4-methylbenzene-l- sulfonyl chloride (0.76 g, 4.0 mmol, 1.1 eq.) portion wise over 20 minutes maintaining the temperature at 0 C. The reaction was allowed to warm to room temperature and stirred overnight. Brine was added and the mixture extracted with dichloromethane (x 2). The combined organic layers were washed with 1 M hydrochloric acid (x 2) and water and the solvent removed in vacuo to afford (i?)-2-hydroxy-2-phenylethyl 4-methylbenzenesulfonate as a white solid (0.817 g, 78% yield). NMR (400 MHz, DMSO) 7.76 (2H, d, J=8.3 Hz), 7.49 (2H, d, J=7.8 Hz), 7.37 - 7.32 (5H, m), 5.81 (1H, d, J=4.6 Hz), 4.81 (1H, dd, J=4.9, 11.3 Hz), 4.07 - 4.04 (1H, m), 2.47 (3H, s).
70% With di(n-butyl)tin oxide; triethylamine; In dichloromethane; at 20℃; General procedure: To a solution of the appropriate alcohol (10mmol) in dry CH2Cl2 (20ml) was added Bu2SnO (0.2mmol) followed by the addition of pTsCl e (10mmol) and TEA (10mmol). The reaction mixture was kept under vigorous stirring at rt for 1-6h. The reaction mixture was quenched by adding water. The solution was extracted with dichloromethane and then combined organic phase were washed with a saturated aqueous solution of brine and dried over anhydrous Na2SO4. The solvent removing in vacuo give a residue that was crystallized or chromatographed to afford the desired compounds (1-5). 4.2.1 (R)-2-hydroxy-2-phenylethyl 4-methylbenzenesulfonate (1) Waxy solid (70%); mp 67-68 C; = - 50.1 (c 1.0, CHCl3). IR (CHCl3) 3220, 3020, 1595, 1451, 1355 cm-1. 1H NMR (CHCl3) δ 7.77 (d, 2H), 7.35-7.26 (m, 7H), 4.98 (dd, J = 8.4, 3.4 Hz, 1H), 4.15 (dd, J = 10.4, 3.4 Hz, 1H), 4.04 (dd, J = 8.4, 10.4 Hz, 1H), 2.45 (s, 3H).
With pyridine; In dichloromethane; at -15℃; for 25h; To a mixture of (R)-phenylethylene glycol, dry pyridine in dry dichloromethane cooled at -15 C. was added portion wise p-toluenesulfonyl chloride over a period of 1 h.The reaction was stirred at -15 C. for 24 h and quenched by adding water.The solution was extracted with dichloromethane and then combined organic phase was washed with aqueous CuSO4, dried (Na2SO4) and concentrated.Silica gel column chromatography of crude product using petroleum ether: EtOAc (4:1) as eluent gave monotosyl compound as a white solid.
With pyridine; In dichloromethane; at 0℃; To a stirred solution of diol (1.0 eq) in DCM(10 mL) was added pyridine (10.0 eq) at 0 C followed by p-toluenesulfonyl chloride (2.0 eq) and the reactionmixture was stirred for 3-4 h at 0 C. After completion of the reaction (TLC),reaction mixture was treated with 10% HCl at 0 C, and extracted with EtOAc(3x20 mL) The combined organic layers were pooled and washed with water (2x20mL) and brine (1x20 mL), dried over anhydrous Na2SO4,filtered, and concentrated. The concentrate was purified by silica gelchromatography (100-200 mesh) using EtOAc/petroleum ether (2:3) to furnish thedesired monotosylated product (75-90% yield).

  • 2
  • potassium cyanide [ No CAS ]
  • [ 16355-00-3 ]
  • [ 40434-87-5 ]
  • [ 73627-97-1 ]
YieldReaction ConditionsOperation in experiment
In ethanol; water; at 0 - 20℃; for 24h; To stirring mixture of monotosyl compound in ethanol-H2O (4:1) at 0 C. was added NaCN in one portion. The reaction mixture was stirred at room temperature for 24 h. The reaction mixture was concentrated at 50 C. on rotatory evaporator and extracted with ethyl acetate. The combined organic phases were washed with brine, dried (Na2SO4) and concentrated. Silica gel column chromatography of crude product using petroleum ether:EtOAc (3:1) as eluent gave (R)-3-phenyl-3-hydroxypropanenitrile as a colorless oil.
 

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