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Structure of 2058-49-3

Chemical Structure| 2058-49-3

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Product Details of [ 2058-49-3 ]

CAS No. :2058-49-3
Formula : C4H10O3S
M.W : 138.19
SMILES Code : CS(=O)(=O)CCCO
MDL No. :MFCD01696727
InChI Key :XPXXXQZNUQAFQY-UHFFFAOYSA-N
Pubchem ID :200424

Safety of [ 2058-49-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H319
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 2058-49-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 31.47
TPSA ?

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

62.75 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.77
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

-0.73
Log Po/w (WLOGP)?

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

0.49
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.

-0.5
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

-0.27
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.05

Water Solubility

Log S (ESOL):?

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

-0.04
Solubility 126.0 mg/ml ; 0.914 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.

-0.11
Solubility 107.0 mg/ml ; 0.774 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

-0.8
Solubility 21.8 mg/ml ; 0.157 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.

-7.66 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

2.0
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

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)

2.25

Application In Synthesis of [ 2058-49-3 ]

* 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 [ 2058-49-3 ]

[ 2058-49-3 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 2058-49-3 ]
  • [ 124-63-0 ]
  • [ 357913-53-2 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at 0℃; for 2.0h; To a solution of 3-methanesulfonyl-propan-1-ol (Cambridge) (0.5 g, 3.6 mmol) in dichloromethane (3 mL) at 0 C. was added triethylamine (0.5 g, 5 mmol), and methanesulfonyl chloride (0.3 mL, 4 mmol, Aldrich). The reaction mixture was stirred at 0 C. for 2 h. The mixture was poured into water, extracted with dichloromethane. The organic layer was separated, washed with water, brine, dried over MgSO4, and concentrated to give crude methanesulfonic acid 3-methanesulfonyl-propyl ester as a yellow oil (Yield 0.7 g, 90%).
With triethylamine; In dichloromethane; at 30℃; for 12.0h; To a solution of 3-methylsulfonylpropan-l-ol (200 mg, 1.45 mmol) in DCM (5 mL) was added Et3N (732 mg, 23.5 mmol) and methanesulfonyl chloride (2.84 g, 24.9 mmol). The mixture was stirred at 30 C for 12 hrs, and then partitioned between H20 (20 mL) and DCM (60 mL). The organic layer was separated, washed with brine (50 mL), dried over anhydrous Na2S04 and concentrated under reduced pressure to afford crude 3-methylsulfonylpropyl methane sulfonate (300 mg) as a yellow oil, which was used directly in the next step without further purification.
With triethylamine; In dichloromethane; at 20℃; for 1.0h; The mixture of the compound 47 (0.100g), methanesulfonyl chloride (0.067 mL), triethylamine (0.120 mL), and a methylene chloride (2.0 mL) was stirred at the room temperature for 1 hour. Water was added to reaction mixed liquor and ethyl acetate extracted. The organic layer was concentrated in vacuum and the rough product of the title compound 48 was obtained. The whole quantity was then used to the next reaction.
  • 2
  • [ 2058-49-3 ]
  • [ 98-59-9 ]
  • [ 263400-88-0 ]
YieldReaction ConditionsOperation in experiment
83% With triethylamine; In dichloromethane; for 12h;Inert atmosphere; 4-Methylbenzene-1-sulfonyl chloride (759 mg, 3.98 mmol), 3-(methylsulfonyl)propan- 1-ol (500 mg, 3.62 mmol) and triethyl amine (0.555 ml_, 3,98 mmol) were dissolved in Dichloromethane Dry (5 mL) under nitrogen atmosphere, and the mixture was stirred for 12 hours. The solvent was removed under reduced pressure and the residue was purified by semi-preparative HPLC-UV, to afford 3-(methylsulfonyl)propyl 4- methylbenzenesulfonate (881 mg, Y = 83%) as a white solid. MS (ESi+) m/z: 293.1 [M+H]+. (0255) Tert-butyl (4-hydroxy-2,6-dimethylphenyl)carbamate (which was synthesized as reported in the synthesis of compound 34) (269 mg, 1.13 mmol), 3- (methysulfonyl)propyl 4-methybenzenesulfonate (398 mg, 1.36 mmol) and potassium carbonate (188 mg, 1.36 mmol) were dissolved in N,N-Dimethylformamide Dry (2.5 ml) and the mixture was stirred at 80C under nitrogen atmosphere for 12 hours. AcOEt (20 mL) was added, and the mixture was washed with brine (2 x 0 mL). The organic layer was concentrated under reduced pressure and the residue was purified by semi-preparative HPLC-UV, to afford tert-butyl (2,6-dimethyl-4-(3- (methylsulfonyl)propoxy)pheny[)carbamate (375 mg, Y = 93%) as a white solid. MS (ESI+) m/z: 380.2 [ +Naf . (0256) Starting from tert-butyl (2,6-dimethyl-4-(3-(methylsulfonyl)propoxy)phenyl)carbamate (375 mg, 1.05 mmol), 2,6-dimethyl-4-(3-(methylsulfonyl)propoxy)aniline, hydrochloride salt (309 mg, Y = quant.) was obtained as reported in the synthesis of compound 34. MS (ESI+) m/z: 258.1 [M+H]+. (0257) Starting from 2,6-dimethyl-4-(3-(methysulfonyl)propoxy)aniline, hydrochloride salt (46.1 mg, 0.157 mmoi) methyl 7-(3-(N-(2,6-dimethyl-4-(3- (methylsulfonyl)propoxy)phenyl)sulfamoyl) (0258) phenyl)heptanoate was obtained (33 mg, Y = 39%) as described in Procedure A. MS (ESI+) m/z: 562.3 [M+Na]+. (0259) Compound 35 was then obtained by hydrolysis of the ester derivative (20 mg, 0.046 mmol) as described for compound 1 , as a white solid (23 mg, Y = 83%). 1H NMR (300 MHz, CHLOROFORM-d) delta ppm 1.24 - 1.43 (m, 4 H) 1.51 - 1 .67 (m, 4 H) 1 .96 (s, 6 H) 2.26 - 2.41 (m, 4 H) 2.61 (t, J=7.58 Hz, 2 H) 2.97 (s, 3 H) 3.22 - 3.31 (m, 2 H) 4.04 (t, .7=5.68 Hz, 2 H) 6.32 (br s, 1 H) 6.52 (s, 2 H) 7.33 - 7.41 (m, 2 H) 7.48 - 7.58 (m, 2 H) 9.36 (br s, 2 H). MS (ESI+) m/z: 526.2 [M+H]+.
1.6 g With pyridine; In dichloromethane; at 0 - 20℃; for 12h; To a solution of 3-(methylsulfonyl)propan-1 -ol (1 .0 g) in dichloromethane (10 mL) and pyridine (1 .5 mL) is added at 0C p-toluene-sulfonylchloride (1 .38 g) in portions. The mixture is stirred for 12 hours at room temperature, diluted with dichloromethane and washed with 1 M aqueous HCI solution and brine. After drying (MgSO4) the solvent is evaporated to give the title compound. Yield: 1 .6 g; LC (method 1 ): tR = 0.82 min; Mass spectrum (ESI+): m/z = 293 [M+H]+.
With dmap; triethylamine; In tetrahydrofuran; at 50℃; for 14h; Step C. 3-(Methylsulfonyl)propyl 4-methylbenzenesulfonate 3-(Methylsulfonyl)propan-l-ol (102 mg, 0.737 mmol), DMAP (0.88 g, 7.2 mmol), and TEA (6.1 ml, 43.4 mmol) were dissolved in THF (29.0 ml). Tosyl chloride (6.1 g, 31.8 mmol) was added and the mixture heated at 50C for 14 hours. The mixture was cooled to RT, diluted with water (300 ml), and extracted with EtOAc (3 x 150 ml). The organic fractions were combined, washed with brine, dried over magnesium sulfate, filtered and the volatiles removed in vacuo. The crude product was purified by column chromotagraphy on silica gel, BIOTAGE (Uppsala, Sweden) HP 340 g, using a gradient eluant of 5-100% EtOAc:Hexanes to the title compound. MS Ret: (m/z): 293 (M+H)+-
With dmap; triethylamine; In tetrahydrofuran; at 50℃; for 14h; Step C. 3-(Methylsulfonyl)propyl 4-methylbenzenesulfonate 3-(Methylsulfonyl)propan-l-ol (102 mg, 0.737 mmol), DMAP (0.88 g, 7.2 mmol), and TEA (6.1 ml, 43.4 mmol) were dissolved in THF (29.0 ml). Tosyl chloride (6.1 g, 31.8 mmol) was added and the mixture heated at 50C for 14 hours. The mixture was cooled to RT, diluted with water (300 ml), and extracted with EtOAc (3 x 150 ml). The organic fractions were combined, washed with brine, dried over magnesium sulfate, filtered and the volatiles removed in vacuo. The crude product was purified by column chromotagraphy on silica gel, BIOTAGE (Uppsala, Sweden) HP 340 g, using a gradient eluant of 5-100% EtOAc:Hexanes to the title compound. MS Ret: (m/z): 293 (M+H)+-
With triethylamine; In dichloromethane; at 0 - 15℃; for 12h; To a stirred solution of 3-methylsulfonylpropan-1-ol (500 mg, 3.62 mmol) in DCM (10 mL) was added triethylamine (549 mg, 5.43 mmol). Then to the mixture was added a solution of tosyl chloride (759 mg, 3.98 mmol) in DCM (10 mL) at 0 C. The resulting mixture was stirred at 15 C for 12 hrs, and then partitioned between DCM and H20. The separated organic layer was washed sequentially with water, hydrochloric acid and brine, then dried over anhydrous Na2SO4 and concentrated under reduced pressure give 3-methylsulfonylpropyl 4-methylbenzenesulfonate (900 mg) as a light yellow oil, which was used directly in the next step without further purification.

 

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