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Chemical Structure| 202658-88-6 Chemical Structure| 202658-88-6

Structure of 202658-88-6

Chemical Structure| 202658-88-6

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Product Details of [ 202658-88-6 ]

CAS No. :202658-88-6
Formula : C3H6ClNO3S
M.W : 171.60
SMILES Code : O=C(NS(=O)(C)=O)CCl
MDL No. :MFCD20637131
InChI Key :BKLFBPWLPOUGTM-UHFFFAOYSA-N
Pubchem ID :23596666

Safety of [ 202658-88-6 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H314-H319
Precautionary Statements:P280-P301+P312-P303+P361+P353-P304+P340-P305+P351+P338-P310
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 202658-88-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.67
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 33.3
TPSA ?

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

71.62 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.1
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

-0.27
Log Po/w (WLOGP)?

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

0.38
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.

-1.04
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

-0.26
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.22

Water Solubility

Log S (ESOL):?

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

-0.54
Solubility 50.0 mg/ml ; 0.291 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.

-0.78
Solubility 28.8 mg/ml ; 0.168 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

-1.21
Solubility 10.6 mg/ml ; 0.0618 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.

-7.54 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

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)

2.08

Application In Synthesis of [ 202658-88-6 ]

* 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 [ 202658-88-6 ]

[ 202658-88-6 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 3144-09-0 ]
  • [ 79-04-9 ]
  • [ 202658-88-6 ]
YieldReaction ConditionsOperation in experiment
94% In ethyl acetate; at 65℃; for 12h;Large scale; In a 2-liter reaction flask, 1 liter of ethyl acetate and 66 grams of methylsulfonamide were added, and 109 grams of chloroacetyl chloride was gradually added; the temperature was gradually increased to 65C for 12 hours until the end of the reaction.The reaction solution gradually cooled to 0 degree, and a large amount of white solid precipitated; it was filtered and dried to obtain 112 g of solid SLP-10b (X=Cl).Yield: 94%.H NMR (400MHz, CDCl3): delta 4.02 (s, 2H), 3.28s, 3H)ESI/MS+(m/z):171
74% In acetic acid butyl ester; for 8h;Heating / reflux; 26.8 mol of chloroacetyl chloride and 25.5 mol of methanesulfonamide in 10.2 L of butyl acetate are slowly boiled at reflux. After 8 h, the mixture is cooled to 20 C. The precipitated solid is filtered off and stirred in 4 L of butyl acetate. The precipitated solid is dried at 50 C. in a fan-assigned drying cabinet. Yield 74%
14 g In acetic acid butyl ester; at 125℃; for 16h; Methane sulfonamide (10 gm) and n-butylacetate (80 mL) were charged into a 250 mL round bottom flask at 30C. Chloroacetylchloride (21 .37 gm) was added slowly over a period of 10 minutes at 30C. Temperature of the reaction mass was raised to 125C and maintained reflux for 16 hours. Progress of the reaction was monitored by TLC and after completion of the reaction the mass was cooled to 20C and stirred for 1 hour at 20C. Reaction mass was filtered and the wet solid was washed with n- butylacetate (10 mL). The wet solid was taken into another 100 mL round bottom flask and n-butylacetate (50 mL) was added and stirred for 30 minutes at 20C. The precipitation was filtered and the solid was suck dried. The material was dried at 45 under vacuum for 5 hours to yield 14 gm of title compound.
  • 2
  • potassium 2,3,3-trimethylindole-5-sulfonate [ No CAS ]
  • [ 202658-88-6 ]
  • [ 324745-40-6 ]
YieldReaction ConditionsOperation in experiment
53% In sulfolane; at 130℃; for 5.83333h; 2.5 mol of G and 2.5 mol of H in 1.3 L of sulfolane are heated at 130 C. After 5 h and 50 min, the mixture is cooled to 50 C. 2.5 L of acetone are added and the mixture is further cooled to room temperature. The precipitated solid is filtered off and washed with acetone. The precipitated solid is stirred in 1.6 L of warm demineralized water. 1.6 L of ethanol are added and the mixture is cooled. The precipitated solid is filtered off and washed with ethanol. Yield: 53%
  • 3
  • [ 202658-88-6 ]
  • C3H5Cl2NO2S [ No CAS ]
  • 4
  • [ 475086-75-0 ]
  • [ 202658-88-6 ]
  • Selexipag [ No CAS ]
YieldReaction ConditionsOperation in experiment
89.7% With potassium tert-butylate; In tetrahydrofuran; at 0 - 5℃; for 1h; To the reaction flask was added 4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]-1-butanol (100 g, 1 eq), THF (1 L), Stir and dissolve;Cooling to 0-5 C; potassium tert-butoxide (155.21 g, 5 eq) was added in portions, temperature control 0-5 C;N-(Chloroacetyl)methylsulfonamide (142 g, 3 eq) was dissolved in tetrahydrofuran (500 mL).Dropped into the above reaction bottle, the temperature is controlled at 0-5 C,The addition is completed in about 1 hour; after the reaction is completed, the reaction is stopped;The reaction solution was concentrated to dryness and dichloromethane (1L) was added.Water (1L); adjust the pH to 5-6 with 1M hydrochloric acid, dispense,The aqueous phase was extracted with dichloromethane (500 mL).The organic phase was washed with water (1 L). The organic phase was concentrated to dryness, anhydrous ethanol (1 L) was added, and the crystals were stirred to give 93.69 g.89.7%, purity 98.5%.
890 mg Potassium tertiary butoxide (700 mg) and dimethylsulfoxide (50 mL) were charged into a 100 mL round bottom flask at 30C. 4-[N-(5,6-diphenylpyrazin-2-yl)-N- isopropylamino]-1 -butanol (1 gm) at 28 C and the resulted mixture was stirred for 15 minutes. <strong>[202658-88-6]2-chloro-N-(methylsulfonyl)acetamide</strong> (1 .2 gm) was added at the resulted was added at the resulted mixture was stirred at 30C for 16 hours. Progress of the reaction was monitored by TLC and after completion of the reaction the reaction mass was poured into cold water and pH was adjusted to 6.5 with 1 N hydrochloric acid (-15 mL). The aqueous layer was extracted with ethylacetate, dried over anhydrous magnesium sulphate and then concentrated. The residue was purified by silica gel column chromatography using 2% Methanol in DCM as eluent to obtain 890 mg of Selexipag.
  • 5
  • [ 475086-75-0 ]
  • [ 202658-88-6 ]
  • C25H30N4O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With potassium tert-butylate; In 1-methyl-pyrrolidin-2-one; at 20℃; for 12h;Large scale; In a 10-liter reaction kettle, 192 g of SLP-9 was dissolved in 2 liters of N-methylpyrrolidone; 67 g of potassium tert-butoxide was slowly added, and then 112 g of SLP-10b (0.7 mol) was added in portions; stirring at room temperature 12 Hours to the end of the reaction.Slowly cool to 0 C., add 2 kg of ice water and add 3 liters of ethyl acetate, stir and stand for phase separation; the organic phase is dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product; the crude product is ethyl acetate/ The petroleum ether crystallized and concentrated to give 219 g of a pale yellow solid SLP-11 (Siripag).Yield: 83%, purity 99.2%.
 

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