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Chemical Structure| 175278-08-7 Chemical Structure| 175278-08-7

Structure of 175278-08-7

Chemical Structure| 175278-08-7

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Product Details of [ 175278-08-7 ]

CAS No. :175278-08-7
Formula : C6H2ClF3O2S
M.W : 230.59
SMILES Code : O=S(C1=CC=C(F)C(F)=C1F)(Cl)=O
MDL No. :MFCD00102573
InChI Key :XFTDZYFHXRZLEF-UHFFFAOYSA-N
Pubchem ID :2776977

Safety of [ 175278-08-7 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314
Precautionary Statements:P280-P305+P351+P338-P310
Class:8
UN#:3265
Packing Group:

Computational Chemistry of [ 175278-08-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 39.4
TPSA ?

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

42.52 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.57
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

2.25
Log Po/w (WLOGP)?

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

4.37
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.

2.81
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

2.68
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.74

Water Solubility

Log S (ESOL):?

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

-2.96
Solubility 0.251 mg/ml ; 0.00109 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.

-2.78
Solubility 0.384 mg/ml ; 0.00166 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

-3.78
Solubility 0.0379 mg/ml ; 0.000164 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

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.

-6.11 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<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)

2.15

Application In Synthesis of [ 175278-08-7 ]

* 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 [ 175278-08-7 ]

[ 175278-08-7 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 1235406-42-4 ]
  • [ 175278-08-7 ]
  • tert-butyl thiazol-4-yl((2,3,4-trifluorophenyl)sulfonyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% EXAMPLE 313 Synthesis of (f?)-2,3-difluoro-4-((1-(1-phenylethyl)piperidin-4-yl)oxy)-//-(thiazol-4- yl)benzenesulfonamide formate Step 1. Preparation of te/f-butyl thiazol-4-yl((2,3,4-trifluorophenyl)sulfonyl)carbamate To a cooled (-50 C) solution of te/f-butyl A/-thiazol-4-ylcarbamate (2.87 g, 14.3 mmol) in tetrahydrofuran (50 mL) was added lithium bis(trimethylsilyl)amide (1 M in tetrahydrofuran, 14.3 mL, 14.3 mmol). The reaction mixture was allowed to warm to ambient temperature and stirred for 30 minutes. The resulting suspension was cooled to 0 C and then added dropwise to a cooled (-78 C) solution of 2,3,4- trifluorobenzenesulfonyl chloride (1.82 mL, 13.0 mmol) in tetrahydrofuran (60 mL). The reaction mixture was allowed to warm to ambient temperature and stirred for 16 h. The reaction mixture was then diluted with saturated aqueous ammonium chloride (50 mL) and extracted with ethyl acetate (3 chi 100 mL). The combined organic layers were washed with brine (2 chi 50 mL), dried over anhydrous sodium sulfate, and filtered. Concentration of the filtrate in vacuo and purification of the residue by column chromatography, eluting with a gradient of 0-30% of ethyl acetate in hexanes, provided the title compound as a colorless solid (4.34 g, 85% yield): MS (ES+) m/z 395.1 (M + 1).
85% To a solution of terf-butyl thiazol-4-ylcarbamate (2.87 g, 14.3 mmol) in anhydrous tetrahydrofuran 50 ml_) was added a 1 M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (14.3 ml_, 14.3 mmol) at -50C. The reaction mixture was allowed to warm to 0 C and stirred for 1 h. After cooling the reaction mixture to 0 C, a solution of 2,3,4-trifluorobenzenesulfonyl chloride (3.0 g, 13.0 mmol) in anhydrous tetrahydrofuran (60 ml_) was slowly added to the reaction mixture. The reaction mixture was allowed to warm to ambient temperature, stirred for 12 h, and then quenched by addition of saturated aqueous ammonium chloride (50 ml_). The mixture was extracted with ethyl acetate (3 c 100 ml_). The combined organic phase was washed with brine (2 c 50 ml_), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The residue was purified by column chromatography, eluting with a gradient of 0-30% of ethyl acetate in heptane, to provide the title compound as a colorless solid (4.34 g, 85% yield): 1H NMR (400 MHz, CDCIs) 8.73 (d, J = 2.2 Hz, 1 H), 7.93 - 7.82 (m, 1 H), 7.47 (d, J = 2.4 Hz, 1 H), 7.11 (ddt, J = 2.2, 6.8, 9.0 Hz, 1 H), 1.29 (s, 9H); MS (ES+) m/z 295.0 (M - 99).
50% To a solution of <strong>[1235406-42-4]tert-butyl thiazol-4-ylcarbamate</strong> (4.90 g, 34.7 mmol) in anhydrous tetrahydrofuran (150 mL) was added a 1 M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (41.6 mL, 41.6 mmol) at -78 C. The reaction mixture was allowed to warm to ambient temperature and stirred for 1 h. The reaction mixture was cooled to -78 C., and a solution of 2,3,4-trifluorobenzenesulfonyl chloride (8.0 g, 34.7 mmol) in anhydrous tetrahydrofuran (20 mL) was added to it. The reaction mixture was allowed to warm to ambient temperature and stirred for 3 h. The mixture was diluted with ethyl acetate (200 mL), washed with saturated ammonium chloride (2×200 mL), brine (2×100 mL), dried over anhydrous sodium sulfate, and filtered. Concentration of the filtrate in vacuo and purification of the residue by column chromatography, eluting with a gradient of 10 to 50% of ethyl acetate in heptane, provided the title compound as a colorless solid (6.70 g, 50% yield): MS (ES+) m/z 395.1 (M+1).
 

Historical Records

Technical Information

• Alkyl Halide Occurrence • Arndt-Eistert Homologation • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Clemmensen Reduction • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hunsdiecker-Borodin Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Preparation of Carboxylic Acids • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Carboxylic Acids • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Ketenes • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

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