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Chemical Structure| 145100-51-2 Chemical Structure| 145100-51-2

Structure of 145100-51-2

Chemical Structure| 145100-51-2

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Product Details of [ 145100-51-2 ]

CAS No. :145100-51-2
Formula : C7H3ClF6N2O4S2
M.W : 392.68
SMILES Code : ClC1=CN=C(N(S(=O)(C(F)(F)F)=O)S(=O)(C(F)(F)F)=O)C=C1
MDL No. :MFCD00191833
InChI Key :TUFGVZMNGTYAQD-UHFFFAOYSA-N
Pubchem ID :388544

Safety of [ 145100-51-2 ]

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

Computational Chemistry of [ 145100-51-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 22
Num. arom. heavy atoms 6
Fraction Csp3 0.29
Num. rotatable bonds 5
Num. H-bond acceptors 11.0
Num. H-bond donors 0.0
Molar Refractivity 61.76
TPSA ?

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

101.17 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.97
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

2.95
Log Po/w (WLOGP)?

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

6.92
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.

-0.09
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

0.86
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.52

Water Solubility

Log S (ESOL):?

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

-4.0
Solubility 0.0388 mg/ml ; 0.0000989 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-4.74
Solubility 0.0072 mg/ml ; 0.0000183 mol/l
Class?

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

Moderately 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

-3.53
Solubility 0.116 mg/ml ; 0.000296 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

Low
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

Yes
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

Yes
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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.6 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

1.0
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

1.0
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)

2.67

Application In Synthesis of [ 145100-51-2 ]

* 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 [ 145100-51-2 ]

[ 145100-51-2 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 53400-41-2 ]
  • [ 145100-51-2 ]
  • [ 890028-85-0 ]
YieldReaction ConditionsOperation in experiment
With potassium hexamethylsilazane; In tetrahydrofuran; at -78 - 20℃; for 16h; To a solution of 1.75 g (12 mmol) of <strong>[53400-41-2]7,8-dihydroquinolin-5(6H)-one</strong> (step A) in dryTEtaF, under nitrogen atmosphere at -78 0C was added dropwise 30.53 mL (1.3 equiv.) of a 0.5 M solution of KEtaMDS in TEtaF. The reaction mixture was stirred at -78 0C to RT over in TEtaF, 2-[N5N- bis(trifluoromethylsulfonylamino)]-5-chloropyridine (5.1 g, 13 mmol) in 30 mL TEtaF was added dropwise. The resulting solution was stirred at RT for 16 hr. and the solvent was removed under vacuum. The residue was dissolved in CEtaCl3; and the resulting mixture was washed with 2 N aq. NaOH, dried over MgSO4 drying agent, filtered and the solvent evaporated under vacuum. This material was purified by column chromatography on silica gel eluting with CHCla/MeOH (95/5) to afford 2.25 g of the title compound that was used for the next step without purification.
  • 2
  • [ 145100-51-2 ]
  • [ 185099-67-6 ]
  • [ 185099-68-7 ]
YieldReaction ConditionsOperation in experiment
92% Part A: Tert-butyl 3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-3-ene-8-carboxylate To a solution of tert-butyl 3-oxo-8-azabicyclo[3.2.1 ]octane-8-carboxylate (450 mg, 2.0 mmol) in THF (15 ml) at -78 C. was added lithium bis(trimethylsilyl)amide (1 M in THF, 2.2 ml, 2.2 mmol) and the reaction solution was stirred for 1 h. A solution of N-(5-chloropyridin-2-yl)-1,1,1-trifluoro-N-(trifluoromethylsulfonyl)methanesulfonamide (864 mg, 2.2 mmol) in THF (20 ml) was added drop wise. The reaction mixture was stirred for another 0.5 h and allowed to warm to room temperature over 3 h and quenched with saturated sodium bicarbonate. The reaction mixture was diluted with ethyl acetate and washed with 15% potassium hydrogen sulfate, saturated sodium bicarbonate solution, 1 N sodium hydroxide, water and brine. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. Flash chromatography (silica gel, 10% ethyl acetate/hexane) gave the product as a colorless oil (659 mg, 92% yield) 1H NMR (400 MHz, CHLOROFORM-D) delta ppm 6.08 (s, 1H), 4.32-4.58 (m, 2H), 2.90-3.15 (m, 1H), 2.23 (br. s, 1H), 1.98-2.07 (m, 3H), 1.67-1.78 (m, 1H), 1.57 (s, 1H), 1.45 (s, 9H).
80% 3.2 3-Trifluorosulfonyl-8-tert-butyloxycarbonyl-8-azabicyclo[3.2.1]-oct-2-ene (N-Boc-nortropanone enol triflate) (104KS22). LDA was generated by adding BuLi (20 mL, 1.68M, 32.6 mmol) to a solution of diisopropylamine (2.38 g, 32.6 mmol) in dry THF (10 mL) at -78 C. under argon. The mixture was kept at that temperature for 30 min followed by the addition of a solution of N-Bocnortropinone (5.27 g, 23.4 mmol) in dry THF (20 mL). The mixture was then left stirring for 1 h while maintaining the temperature at 78 C. Then a solution of 2-[N,N-Bis(trifluoromethylsulfonyl)amino]-5-chloropyridine (10.08 g, 25.7 mmol) in dry THF (20 mL) and the mixture was slowly allowed to reach room temperature overnight and subsequently concentrated and exposed to column chromatography (SiO2; EtOAc/heptane 1:6, Rf(product)=0.31) to give the title compound (104KS22) (6.68 g, 80%) which on prolonged standing crystallized into a white solid. 1H NMR (CDCl3) delta 1.43 (s, 9H, Boc-C3), 1.72 (m, 1H), 1.93-2.03 (m, 2H), 2.07 (d, J=16.6 Hz, 1H), 2.23 (broad m, 1H), 3.05 (broad s, 1H), 4.42 (broad m, 2H, H1+H5), 6.10 (broad s, 1H, H2). 13C NMR (CDCl3) delta 28.4 (Boc H3), 30.1 and 29.2 (rotameric), 34.7 and 34.9 (rotameric), 36.5 and 37.1 (rotameric), 51.9, (broad s), 80.5 ((CH3)3-), 118.7 (-F3, q, J=300 Hz), 124.0 (broad s, C2), 148.0 (broad s, C3), 153.9 (Boc C=O).
  • 3
  • [ 145100-51-2 ]
  • [ 1655-07-8 ]
  • [ 122135-83-5 ]
  • 4
  • [ 3883-58-7 ]
  • [ 145100-51-2 ]
  • 1,4-bis[(trifluoromethanesulfonyl)oxy]-5,5-dimethylcyclopenta-1,3-diene [ No CAS ]
  • 5
  • [ 7467-91-6 ]
  • [ 145100-51-2 ]
  • quinoxalin-6-yl triflate [ No CAS ]
 

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