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Chemical Structure| 90536-66-6 Chemical Structure| 90536-66-6

Structure of 90536-66-6

Chemical Structure| 90536-66-6

2-(4-(Methylsulfonyl)phenyl)acetic acid

CAS No.: 90536-66-6

4.5 *For Research Use Only !

Cat. No.: A314848 Purity: 97%

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Product Details of [ 90536-66-6 ]

CAS No. :90536-66-6
Formula : C9H10O4S
M.W : 214.24
SMILES Code : O=C(O)CC1=CC=C(S(=O)(C)=O)C=C1
MDL No. :MFCD00216495
InChI Key :HGGWOSYNRVOQJH-UHFFFAOYSA-N
Pubchem ID :572345

Safety of [ 90536-66-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H319
Precautionary Statements:P305+P351+P338

Computational Chemistry of [ 90536-66-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 51.08
TPSA ?

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

79.82 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.96
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

1.32
Log Po/w (WLOGP)?

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

1.8
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.

1.16
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

0.88
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.22

Water Solubility

Log S (ESOL):?

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

-2.12
Solubility 1.63 mg/ml ; 0.0076 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.

-2.6
Solubility 0.542 mg/ml ; 0.00253 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

-2.5
Solubility 0.685 mg/ml ; 0.0032 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

No
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.

-6.67 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.

0.56

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)

1.64

Application In Synthesis of [ 90536-66-6 ]

* 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 [ 90536-66-6 ]

[ 90536-66-6 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 5470-70-2 ]
  • [ 90536-66-6 ]
  • [ 221615-75-4 ]
YieldReaction ConditionsOperation in experiment
With tert-butylmagnesium chloride; In tetrahydrofuran; at 65 - 70℃; for 1.5h; In a 4-neck anhydrous flask there are introduced at 20-25C 5.0 g of (4-methylsulfonyl)phenyl acetic acid of formula (IV) (1.0 mol. equiv.), 100 mL of Anhydrous THF and the mixture is heated to 65-70C (up to reflux). Maintaining at T=65-70 C there are simultaneously dosed in the mixture in about 1 hour: a) 62.0 g of t-BuMgCl 1.0 M solution in THF (about 70.0 mL) (3.0 mol. equiv.) andb) a solution of 2.3 g of methyl ester of 6-methylpyridine-3-carboxylic acid of formula (III - R=Me) (0.65 mol. equiv.) in 7.5 mL of Anhydrous THF. After completing addition, maintain at 65-70 C for 30 minutes. The reaction is controlled through HPLC: HPLC purity 72.05% (A%) and Impurity '408' = 0.26% (A%).
1.8 kg With tert-butylmagnesium chloride; In tetrahydrofuran; at 70 - 80℃;Large scale; 4-methanesulfonylphenylacetic acid (3.0 kg) was added tetrahydrofuran (6 L),A solution of 1 M t-butylmagnesium chloride in tetrahydrofuran (40 L) was added dropwise,Heating 70 ~ 80 ,A solution of methyl 6-methylnicotinate (1.7 kg) in tetrahydrofuran (5 L) was slowly added dropwise,About 2 to 3 hours dripping.After refluxing for 1 hour.Cooling to 20 ~ 25 ,add water,The pH of the sodium hydroxide aqueous solution (the mass concentration refers to the mass of sodium hydroxide as a percentage of the total mass of the aqueous sodium hydroxide solution) is adjusted to pH = 7 to 8,Precipitate a lot of solid.Centrifugal,The filter cake was rinsed with water and dried in vacuo at 50 C for 16 hours,About 3.6 kg of a yellow solid was obtained.Recrystallization from dichloromethane (20 L) gave 1.8 kg of etoposide intermediate II.
  • 2
  • [ 5470-70-2 ]
  • [ 90536-66-6 ]
  • [ 1421227-97-5 ]
  • [ 221615-75-4 ]
YieldReaction ConditionsOperation in experiment
In an anhydrified 4-neck flask there were introduced at 20-25C 5.0 g of (4-methylsulfonyl)phenyl acetic acid of formula (IV) and 100 mL of anhydrous THF and stirring is carried out at 20-25C. 1.0 g of sodium hydride dispersion in mineral oil (60% w/w, MW: 24.00; 1.1 molar equivalents) is added in portions in about 5 minutes, ensuring that the temperature does not exceed 45-50C. After completing the addition the mixture is heated to 65-70C for 1 hr. Maintaining at T=65-70C there are rapidly added 21 g (1.0 equiv.) of t-BuMgCl 1.0 M solution in THF (PM116.87) (23 mL). The mixture is left under stirring for 1 hr at 65-70C then is rapidly added, still at 65-70C, a solution of 1.78 g (0.5 equiv.) of methyl ester of the 6-methylpyridine-3-carboxylic acid of formula (III - R=Me) in 5 ml of Anhydrous THF. After completing the addition the mixture is maintained at 65-70C for 1 hr. Maintaining at T=65-70C there are rapidly added 10.5 g (0.5 equiv.) of t-BuMgCl 1.0 M solution in THF (PM 116.87) (11.5 mL). The mixture is left under stirring for 1 hr at 65-70C then there is rapidly added, still at 65-70C, a solution of 260 mg (0.075 equiv.) of methyl ester of 6-methylpyridine-3-carboxylic acid of formula (III - R=Me) in 1 mL of anhydrous THF. After completing addition the mixture is maintained at 65-70 C for 1 hr. Maintaining at T=65-70 C there are rapidly added 10.5 g (0.5 equiv.) of t-BuMgCl 1.0 M solution in THF (PM 116.87) (11.5 mL). The mixture is left under stirring for 1 hr at 65-70 C then there is rapidly added, still at 65-70 C, a solution of 260 mg (0.075 equiv.) of methyl ester of the 6-methylpyridine-3-carboxylic acid of formula (III - R=Me) in 1 mL of Anhydrous THF. After completing addition the mixture is maintained at 65-70 C for 1 hr. Cooling is carried out to 20-25C. The yield is calculated in solution through titration: 80%. The product is isolated according to the preceding example. It is obtained a molar yield equivalent to 73% and with 94.4% HPLC purity (A%) and amount of impurity '408' = 2.02% (A%) (see figure 4).
  • 3
  • [ 90536-66-6 ]
  • [ 1421227-97-5 ]
  • [ 221615-75-4 ]
 

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