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Chemical Structure| 914610-39-2 Chemical Structure| 914610-39-2

Structure of 914610-39-2

Chemical Structure| 914610-39-2

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Product Details of [ 914610-39-2 ]

CAS No. :914610-39-2
Formula : C17H27BN2O4S
M.W : 366.28
SMILES Code : O=S(N1CCN(C)CC1)(C2=CC=C(B3OC(C)(C)C(C)(C)O3)C=C2)=O
MDL No. :MFCD09746210
InChI Key :TZMSTBRAQGYDJI-UHFFFAOYSA-N
Pubchem ID :23154502

Safety of [ 914610-39-2 ]

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

Computational Chemistry of [ 914610-39-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 25
Num. arom. heavy atoms 6
Fraction Csp3 0.65
Num. rotatable bonds 3
Num. H-bond acceptors 6.0
Num. H-bond donors 0.0
Molar Refractivity 106.75
TPSA ?

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

67.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

1.87
Log Po/w (WLOGP)?

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

1.24
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.

0.56
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

0.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.78

Water Solubility

Log S (ESOL):?

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

-3.27
Solubility 0.197 mg/ml ; 0.000539 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.

-2.91
Solubility 0.452 mg/ml ; 0.00123 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

-4.04
Solubility 0.0334 mg/ml ; 0.0000912 mol/l
Class?

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

Moderately 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

Yes
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.

-7.21 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)

3.56

Application In Synthesis of [ 914610-39-2 ]

* 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 [ 914610-39-2 ]

[ 914610-39-2 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 837-12-7 ]
  • [ 73183-34-3 ]
  • [ 914610-39-2 ]
YieldReaction ConditionsOperation in experiment
65% With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In toluene;Inert atmosphere; Reflux; l-Methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonyl]plperazlne (955-2)Pd(PPh3)* (3 g) was added to a mixture of l-(4-bromophenyl sulfonyl)-4-methylpiperazine (20 g, 62.6 mmol), plnacolatodlboron (11 g, 62.6 mmol), and potassium carbonate (17.8 g, 0.13 mol) In toluene (1 L) under nitrogen protection. The mixture was heated under reflux overnight. After cooling to room temperature, the solvent was removed under vacuum. To the residue were added water (500 ml) and ethyl acetate (500 ml). The organic phase was collected, and the water phase was extracted with ethyl acetate (500 ml x2). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to afford 1- methyl-4-[4- (4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonyl]piperazlne (955-2, 15.1 g, yield 65%). LC-MS: 367.2 (M+l).
65% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; for 12h;Inert atmosphere; Reflux; To a mixture of 1-(4-bromophenyl sulfonyl)-4-methylpiperazine (1) (20g, 62.6mmol), pinacolatodiboron (11g, 62.6mmol), and potassium carbonate (17.8g, 0.13mol) in toluene Pd(PPh3)4 (3g) was added (1 L) under nitrogen protection. The mixture was heated under reflux overnight. After cooling to RT, the solvent was removed under vacuum. To the residue were added water (500mL) and EA (500mL). The organic phase was collected, and the water phase was extracted with EA (500mL×2). The organic phases were combined, dried over anhydrous sodium sulfate and concentrated to afford 2 (15.1g, yield 65%). LC-MS: 367.2 (M+l).
With 1,1'-bis-(diphenylphosphino)ferrocene; potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 90℃; for 8h;Heating; 1. 2-R2-(4-METHOXVPYRIDIN-2-VL) ETHVLL-6-S-(4-METHYLPIDERAZIN-1-YL-SULFONVL) PHENYLLTH-IMIDAZO- [45-BLPYRIDINE A mixture of 1.12 g of 1- (4-BROMO-BENZENE-SULFONYL)-4-METHYL-PIPERAZINE, 0.978 g of bis- (pinacolato)- diboron, 0.06 g OF 1, 1 -BIS- (DIPHENYLPHOSPHINO)-FERROCENE, 0.077 g of [1,1'-bis (diphenyl- phosphino) ferrocene] palladium-dichloride (complex with CH2CI2), 1.03 g of potassium acetate in 40 ML of degassed dioxane are heated to 90C under N2 FOR 8 hours. To the resulting mixture 15 ml of degassed dioxane, 0.931 g of 2- [2- (4-methoxypyridin-2-yl) ethyl]-6-iodo-3H-imidazo [4,5-b] pyridine (starting material A1), 0.283 g OF TETRAKIS (TRIPHENYLPHOSPHINE)-PALLADIUM (0) and a solution of 0.678 G of potassium carbonate and 0.208 g of lithium chloride in 15 ml of degassed water are added under N2. The mixture is heated to reflux under N2 for 16 hours and, after cooling, addition of water and adjusting the pH to 7, it is extracted three times with DICHLOROMETHANE. The combined organic phases are dried over sodium sulfate, concentrated and the residue is chromatographed on a silica gel column (DICHLOROMETHANELMETHANOL 15-10: 1). Concentration of the chromatographically pure fractions and crystallization of the residue from ETHYLACETATE gives 0.545 g of the title compound as a solid of m. p. 193-195C. The mass spectrum shows the molecular peak MHS at 493.4 Da.
  • 2
  • [ 837-12-7 ]
  • [ 914610-39-2 ]
YieldReaction ConditionsOperation in experiment
With potassium acetate; bis(pinacol)diborane;1,1'-bis-(diphenylphosphino)ferrocene; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 90℃; for 24h; 1. 1-(2-lmidazol-1-yl-pyrimidin-5-yl)-1-[4'-(4-methyl-piperazine-1-sulfonyl)-biphenyl-4-yl]- methanone; 492 mg of 1-(4-Bromo-benzenesulfonyl)-4-methyl-piperazine (compound A1 ) are dissolved in 7 ml of oxygen-free dioxane under an atmosphere of dry nitrogen. Subsequently, 429 mg of bis(pinacolato)- diboron, 34 mg of Pd(CI)2(dppf) ' CH2CI2, 26 mg of DPPF (1 ,1'- bis(diphenylphosphino)-ferrocene), and 453 mg of potassium acetate are added. The reaction mixture is heated at 9O0C for 24 hours during which time the former yellowish suspension becomes black (LC-MS monitoring for formation of boronic ester intermediate). Thereafter, 329 mg of 1-(4-bromo-phenyl)-1-(2-imidazol-1-yl-pyrimidin-5-yl)- methanone (compound B1 ), 276 mg of potassium carbonate, 85 mg of lithium chloride, 1 16 mg of Pd(PPh3)4, 11 ml of oxygen-free dioxane, and 11 ml of water are added. The reaction mixture is heated at 9O0C and stirring is continued for 16 hours. Subsequently, the suspension is concentrated in vacuo and co-evaporated twice with 20 ml each of toluene. The resulting crude material is purified by chromatography (eluent: dichloromethane/ethanol 20:1 parts per volume) to afford 165 mg of the title compound as a colorless solid. M. p. 2520C. ESI-MS: 489.3 (MH+). TLC: Rf = 0.56 (dichloromethane/methanol 10:1 parts per volume).
  • 3
  • [ 837-12-7 ]
  • [ 73183-34-3 ]
  • [ 914610-39-2 ]
  • C22H30N4O4S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium acetate; palladium diacetate; In N,N-dimethyl-formamide; at 80℃; for 4h;Inert atmosphere; A 50 mL round bottom flask was charged with 1-(4-bromophenylsulfonyl)-4-methylpiperazine (110 mg, 0.350 mmol), bis-(pinacolato)-diboron (93 mg, 0.37 mmol), palladium acetate (6 mg, 0.02 mmol), and potassium acetate (103 mg, 1.05 mmol) in N,N-dimethylformamide (6 mL). The mixture was degassed by gently bubbling argon through the solution for 30 minutes at room temperature. The mixture was then heated at 80 C. under argon until the reaction was complete (4 hours). The required product, 1-methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonyl-piperazine, and the bi-aryl product, 4-(4-methylpiperazin-1-ylsulfonyl)phenyl-phenylsulfonyl-4-methylpiperazine, were obtained in a ratio of 1:2 as indicated by LC/MS analysis.
 

Historical Records

Technical Information

Categories

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[ 914610-39-2 ]

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[ 914610-39-2 ]

Piperazines

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