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Chemical Structure| 5345-27-7

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Product Details of [ 5345-27-7 ]

CAS No. :5345-27-7
Formula : C8H8O4S
M.W : 200.21
SMILES Code : O=C(O)C1=CC=CC(S(=O)(C)=O)=C1
MDL No. :MFCD00216488
Boiling Point : No data available
InChI Key :KUTBMATZUQWFSR-UHFFFAOYSA-N
Pubchem ID :220380

Safety of [ 5345-27-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 5345-27-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 46.5
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.

0.83
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

0.48
Log Po/w (WLOGP)?

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

1.87
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.

1.11
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

0.53
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.96

Water Solubility

Log S (ESOL):?

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

-1.59
Solubility 5.11 mg/ml ; 0.0255 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.73
Solubility 3.77 mg/ml ; 0.0188 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very 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

-2.09
Solubility 1.63 mg/ml ; 0.00817 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.

-7.18 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)

1.74

Application In Synthesis of [ 5345-27-7 ]

* 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 [ 5345-27-7 ]

[ 5345-27-7 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 5345-27-7 ]
  • [ 220798-39-0 ]
YieldReaction ConditionsOperation in experiment
90% With borane-THF; In tetrahydrofuran; at 20℃; for 12h; A solution of 3- (methylsulfonyl) benzoic acid (1.0 g, 5.0 mmol) in anhydrous THF (25 mL) was treated with BH3. THF (1 M solution, 7.5 mL) at room temperature. The reaction was stirred for 12 hours before it was quenched by slow addition of MeOH. The solvent was removed and the residue was purified by flash column chromatography (0-5 % MeOH in CH2CI2) to give the product (0.84 g, 90% yield NMR (300 MHz, CDCI3) 5 : 3.06 (s, 3 H), 4.81 (d, J = 6.0 Hz, 2 H), 7.54-7. 59 (m, 1 H), 7. 65-7.68 (m, 1 H), 7.85-7. 88 (m, 1 H), 7.96 (s, 1 H).
63% With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 15℃; for 14h; To a solution of 34 (2.00 g , 9.99 mmol) in THF (10 mL) was added UAIH4(758 mg, 20.0 mmol) at 0 C. The mixture was stirred at 15 C for 14 h. The mixture was cooled to 0 C and quenched by saturated solution of potassium sodium tartrate (2mL), the precipitate formed was collected, filtered to remove the precipitate. The organic phase was concentrated in vacuo to give 35 (1 .40 g, 63%).1H N R (400 MHz, CDCI3) 7.97 (s, 1 H), 7.87 (d, J - 7.5 Hz, 1 H), 7.67 (d, J - 7.9 Hz, 1 H), 7.63 - 7.53 (m, 1 H), 4.82 (d , J = 5.7 Hz, 2H), 3.07 (s, 3H).
51% With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; (13A) [3-(Methylsulfonyl)phenyl]methanol 3-(Methylsulfonyl)benzoic acid (540 mg, 2.70 mmol) was dissolved in tetrahydrofuran (40 mL), and the resulting solution was cooled to 0 C. Then, lithium aluminum hydride (102 mg, 2.70 mmol) was added thereto, and the temperature of the resulting mixture was raised to room temperature, and the mixture was stirred for 3 hours. Water was added to the reaction solution, and the organic matter was extracted with ethyl acetate. The organic layer was washed with water and a saturated sodium chloride solution, then dried over anhydrous magnesium sulfate and filtered. Then, the solvent was distilled off under reduced pressure, whereby a crude product was obtained. This crude product was purified by silica gel column chromatography (hexane:ethyl acetate=100:0 to 70:30 (v/v)), whereby the objective title compound was obtained as a colorless oily substance (257 mg, yield: 51%). 1H NMR (CDCl3, 400 MHz): delta1.26 (1H, brs), 3.06 (3H, s), 4.81 (2H, d, J=5.5 Hz), 7.57 (1H, t, J=7.8 Hz), 7.67 (1H, d, J=7.5 Hz), 7.86 (1H, d, J=7.5 Hz), 7.96 (1H, s)
42% With lithium aluminium tetrahydride; In tetrahydrofuran; diethyl ether; for 1h;Heating / reflux; To an ice-cold solution of 3- (methylsulfonyl) benzoic acid (1.4 g, 7.1 mmol) in 2: 1 Et20/THF (60 mL) was added LIALH4 (8.5 mL of 1.0 M solution in THF, 8.5 mmol), and the reaction mixture was heated at reflux for 1 h. The reaction mixture was cooled to 0 C, and the reaction was quenched with water (15 mL) and 15% NaOH in water (35 mL). The reaction mixture was filtered, concentrated under reduced pressure, and the residue was dissolved in EtOAc. The organic solution was washed with water and then brine, dried (MGS04), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 1: 2 to 3: 1 EtOAc/hexanes) provided (3- methanesulfonyl) phenyl methanol as a clear oil (0.56 g, 42%) :H NMR (300 MHz, CDC13) 5 7.93 (s, 1H), 7.83 (d, J = 7 Hz, 1H), 7.64 (d, J = 7 Hz, 1H), 7.53 (t, J = 7 Hz, 1H), 4. 78 (d, J = 6 Hz, 2H), 3.05 (s, 3H), 2.61 (br s, 1H).
With borane-THF; In tetrahydrofuran; at 0 - 20℃; for 0.166667h; To an ice-cooled stirring solution of 1M BH3 in THF (25 ml_, 25 mmol) under inert atmosphere is added dropwise over a 10 minutes period a solution of 3- methanesulfonylbenzoic acid (2g, 10 mmol) in THF (20 mL). The reaction mixture is stirred at room temperature overnight then cooled down to 0C before adding water (2 mL). The solvent is removed under reduced pressure and the residue is partitioned between DCM and NaOH. The organic layer is isolated and dried over MgSO4 and filtered. The solvent is removed under reduced pressure to give (3-methanesulfonyl-phenyl)-methanol; [M-H]' 185.
With borane-THF; In tetrahydrofuran; at 0 - 20℃; (3-Methanesulfonyl-phenyl)-methanol was prepared as follows: To 3- Methanesulfonyl-benzoic acid in THF at O0C was added dropwise a borane-THF complex and the reaction mixture stirred at room temperature overnight. Excess hydride was destroyed by slow addition of a water/THF mixture. The aqueous phase was saturated with potassium carbonate then extracted with ether. The organics were dried with MgSO4 and the solvent reduced in vacuo to yield (3-methanesulfonyl-phenyl)- methanol as a clear oil.
Borane solution (1M in THF) was added dropwise to a stirred mixture of 3-methylsulfonyl)benzoic acid (400 mg, 2.00 mmol) in anhydrous THF (2 ml) at 0 C. The resulting mixture was then allowed to warm to room temperature and stirred for 3 h. The reaction mixture quenched with water/1 M HCl (aq.), extracted with ethyl acetate (3 times), the combined organic extracts dried (sodium sulfate) and concentrated in vacuo to give crude (3-(methylsulphonyl)phenyl)methanol as an oil which was used in the next step without further purification. The alcohol was dissolved in dichloromethane (6 ml) and triethylamine (0.418 mL, 3.0 mmol). Methanesulfonylchloride (first batch (0.186 mL, 2.4 mmol) was then added, followed by a second batch (0.039 mL, 0.5 mmol) and the resulting mixture was stirred for 16 h. 1 N HCl solution (aq.) was then added and the reaction mixture was extracted with diethyl ether (3 times), the combined organic extracts were dried (sodium sulfate) and concentrated in vacuo. The residue was purified by column chromatography eluting using a gradient (petroleum ether 40/60/ethyl acetate 1:0 v/v 0:1) to afford 212 mg (52% over 2 steps) of the title compound as an oil. 1H NMR (CDCl3): 7.98 (1H, s), 7.91 (1H, d, J 7.8), 7.70 (1H, d, J 7.8), 7.59 (1H, t, J 7.8), 4.65 (2H, s), 3.08 (s, 3H).
To a solution of Intermediate AX (l.Og, 4.99 mmol) in THF (20mL) at 0 C was added a solution of BH3DMS (0.94 mL, 9.98 mmol). After the addition was complete, the reaction mixture was stirred at 70 C for 1 hour. The reaction mixture was cooled, methanol (5.0 mL) was added, and the mixture was refluxed for 30 minutes. Solvent from the reaction mixture was removed via distillation, and the residue was diluted with ethyl acetate (30 mL), washed with water (2 x 15 mL) and brine (15 mL), dried over dried over anhydrous Na2S04, and the solvent was removed to afford the crude Intermediate AY (720mg, 77%) as an off white solid. This material was used in the next step without further purifications. NMR (CDC13): delta 7.95 (s, 1H), 7.85 (d, J = 7.88 Hz; 1H), 7.66 (d, J= 7.88 Hz, 1H), 7.56 (t, J= 7.65 Hz; 1H), 4.80 (s, 2H), 3.06 (s, 3H). Mass (M+H): 187.0.
With borane-THF; boron trifluoride diethyl etherate; In tetrahydrofuran; at 0 - 20℃; To a solution of 3-(methylsulfonyl)benzoic acid (1.2 g, 6:0 mmol) in THF (30 ml.) at 0 0C, is added equimolar amounts of borane (6.0 ml_ of a 1.0 M solution in THF) and boron trifluoride diethyl etherate (0.8 ml_, 6.0 mmol). The reaction is allowed to warm to ambient temperature overnight, and then quenched by pouring into a mixture of ice and solid NaHCO3. Following extraction with EtOAc, the organic layer is washed with brine and dried over Na2SO4. Removal of solvent affords the product as a colorless oil: MS (M+NH4)+ = 204.

 

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