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Structure of 74853-08-0

Chemical Structure| 74853-08-0

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Product Details of [ 74853-08-0 ]

CAS No. :74853-08-0
Formula : C16H19N3O
M.W : 269.34
SMILES Code : OC1=CC=C(N2CCN(C3=CC=C(N)C=C3)CC2)C=C1
MDL No. :MFCD02093082
InChI Key :WZIJMPVPOMTRNM-UHFFFAOYSA-N
Pubchem ID :10221065

Safety of [ 74853-08-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 74853-08-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 20
Num. arom. heavy atoms 12
Fraction Csp3 0.25
Num. rotatable bonds 2
Num. H-bond acceptors 1.0
Num. H-bond donors 2.0
Molar Refractivity 89.37
TPSA ?

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

52.73 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.93
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

2.6
Log Po/w (WLOGP)?

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

1.55
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.

1.87
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

1.35
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.86

Water Solubility

Log S (ESOL):?

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

-3.46
Solubility 0.0934 mg/ml ; 0.000347 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.

-3.36
Solubility 0.119 mg/ml ; 0.00044 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

-3.76
Solubility 0.0465 mg/ml ; 0.000173 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

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

Yes
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

Yes
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.

-6.1 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.

2.0 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<0.0
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)

1.79

Application In Synthesis of [ 74853-08-0 ]

* 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 [ 74853-08-0 ]

[ 74853-08-0 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 1885-14-9 ]
  • [ 74853-08-0 ]
  • [ 184177-81-9 ]
YieldReaction ConditionsOperation in experiment
94.6% In tetrahydrofuran; at 0 - 25℃;Large scale; Will be 4.00kg1- (4-aminophenyl) -4- (4-hydroxyphenyl) piperazine (VII) and 35.57 kg of tetrahydrofuran100L glass reactor, open the stirring, cooling to 0 ~ 10 .Maintain the temperature below 25 drop 2.56kgPhenyl chloroformate (VIII),0.5 to 1 hour drop finished, temperature control 20 ~ 25 to continue the reaction of 0.5 to 1.0 hours. TLC monitoring reaction, the reaction finishedAfter the completion of the cooling to 0 ~ 10 ,Add saturated aqueous sodium bicarbonate solution (sodium bicarbonate 2.00kg dissolved in purified water 38kg), then add purified water 20kg,Stirring for 10 ~ 20min. Centrifuge the filter to the basic solvent-free effluent, and then rinse with 8kg of purified water, centrifugal rejection to the basic solvent-free effluent.The whole batch of wet goods in the vacuum -0.06MPa ~ -0.1MPa, the control temperature of 40-50 conditions,Dry under reduced pressure 12 to 16 hours. 5.47 kg of a gray solid,Phenyl (4- (4- (4-hydroxy) -1-piperazinyl) phenyl) carbamate(V);HPLC purity: 98.5% yield: 94.6%
215 g In N,N-dimethyl-formamide; at 0 - 30℃; for 3h; Example-8 Preparation of Phenyl-4-(4-(4-hydroxyphenyl)piperazin-1-yl)phenyl carbamate (Formula-19) Phenyl chloroformate (139.5 g) was added to a pre-cooled solution of 4-(4-(4-aminophenyl)piperazin-1-yl)phenol compound of formula-18 (200 g) in dimethyl formamide (1400 ml) at 0-10 C. Temperature of the reaction mixture was raised to 25-30 C. and then stirred for 3 hours at 25-30 C. After completion of the reaction, the reaction mixture was quenched with water. Filtered the precipitated solid and washed with water.
In N,N-dimethyl-formamide; at 0 - 10℃; Phenyl chloroformate (13.95 g, 0.089 mol) was added to a pre-cooled solution of compound 2 (20 g, 0.074 mol) in dimethylformamide (140 mL) at 0-10 C. After the completion of the reaction, the reaction mixture was quenched with water. Ispropyl alcohol (IPA, 60 mL) was added to the solid and the mixture was heated to 60-65 C and stirred for 1 h at the same temperature. Compound 4 was filtered off, washed with IPA, and dried. 1H NMR (DMSO-d6, 400 MHz): delta 3.155 (t, 8H, piperazine-CH2), 6.685 (d, 2H, p-aminophenol-3-CH), 6.859 (d, 2H, p-aminophenol-2-CH), 6.981 (d, 2H, aniline-3-CH), 7.237 (m, 2H, aniline-2-CH), 7.406 (t, 2H, phenol-CH), 7.447 (d, 2H, phenol-CH), 8.871 (s, 1H, p-aminophenol-OH), 9.989 (s, 1H, CO2NH). IR (KBr, lambda, cm-1) 3460 (s), 3368 (m), 1662 (s), 1568 (s), 1340 (s), 1160(s).
 

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Technical Information

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