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Chemical Structure| 478646-28-5 Chemical Structure| 478646-28-5

Structure of 478646-28-5

Chemical Structure| 478646-28-5
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Product Details of [ 478646-28-5 ]

CAS No. :478646-28-5
Formula : C13H19NO4
M.W : 253.29
SMILES Code : O=C(OCC1=CC=CC=C1)N[C@H](CCCO)CO
MDL No. :MFCD03426376
InChI Key :QONUZQBHASYEAL-GFCCVEGCSA-N
Pubchem ID :2757382

Safety of [ 478646-28-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 478646-28-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 6
Fraction Csp3 0.46
Num. rotatable bonds 9
Num. H-bond acceptors 4.0
Num. H-bond donors 3.0
Molar Refractivity 67.05
TPSA ?

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

78.79 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.08
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

0.85
Log Po/w (WLOGP)?

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

0.89
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.

0.98
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

1.4
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.24

Water Solubility

Log S (ESOL):?

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

-1.6
Solubility 6.38 mg/ml ; 0.0252 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.

-2.09
Solubility 2.07 mg/ml ; 0.00817 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

-3.06
Solubility 0.218 mg/ml ; 0.000861 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.

-7.24 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

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)

2.85

Application In Synthesis of [ 478646-28-5 ]

* 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 [ 478646-28-5 ]

[ 478646-28-5 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 478646-28-5 ]
  • [ 1384476-35-0 ]
  • [ 1384476-36-1 ]
  • 2
  • [ 478646-28-5 ]
  • [ 1384476-04-3 ]
  • 3
  • [ 478646-28-5 ]
  • [ 1384476-41-8 ]
  • [ 1384476-42-9 ]
  • [ 1384476-43-0 ]
  • 4
  • [ 478646-28-5 ]
  • [ 1384476-05-4 ]
  • [ 1384476-06-5 ]
  • [ 1384476-07-6 ]
  • 5
  • [ 478646-28-5 ]
  • [ 1384476-05-4 ]
  • [ 1384476-07-6 ]
  • 6
  • [ 478646-28-5 ]
  • [ 1384476-08-7 ]
  • 7
  • [ 478646-28-5 ]
  • (2R)-2-aminopentan-1,5-diol [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% With palladium 10% on activated carbon; hydrogen; In ethanol; under 760.051 Torr; for 1.5h; Example 68A (2R)-2-Aminopentan-1,5-diol 500 mg of <strong>[478646-28-5](R)-2-Cbz-aminopentan-1,5-diol</strong> were dissolved in 250 ml of ethanol, a spatula tip of Pd/C (10%) was added and the mixture was hydrogenated with hydrogen at atmospheric pressure for 90 minutes. The reaction mixture was filtered through kieselguhr, the filter cake was washed with ethanol and the filtrate was concentrated. This gave 183 mg (78% of theory) of the target compound which was reacted further without further purification. 1H NMR (400 MHz, DMSO-d6): delta=1.00-1.15 (m, 1H), 1.30-1.65 (m, 3H), 2.55 (m, 1H; partially obscured by DMSO signal), 3.10 (dd, 1H), 3.28 (dd, 1H), 3.40 (t, 2H; partially obscured by water signal), 4.50 (br.s, 1H).
  • 8
  • [ 478646-28-5 ]
  • tert-butyl N-[(2R)-1,5-dihydroxypentan-2-yl]carbamate [ No CAS ]
  • 9
  • [ 478646-28-5 ]
  • [ 108-24-7 ]
  • [ 1384476-38-3 ]
  • [ 1384476-39-4 ]
  • [ 1384476-40-7 ]
  • 10
  • [ 478646-28-5 ]
  • [ 1609164-89-7 ]
  • 11
  • [ 6893-26-1 ]
  • [ 478646-28-5 ]
  • 12
  • [ 16422-27-8 ]
  • [ 478646-28-5 ]
  • 13
  • [ 67436-17-3 ]
  • [ 478646-28-5 ]
YieldReaction ConditionsOperation in experiment
90.8% With sodium tetrahydroborate; ethanol; In tetrahydrofuran; at 0 - 15℃; In a dropping funnel,Thermometer dry four bottles,150 g of a compound of formula V (eta = 2) was added,And 150 g of tetrahydrofuran,Stirring dissolved after cooling to 0 ~ l0 C,29 g of sodium borohydride was added,Further, 72 g of anhydrous ethanol was added,Insulation in the 10 ~ 15 C reaction to the raw material reaction is complete by adding 90g acetic acid,The pH of the reaction solution was adjusted to 4 to 5, and 330 g of water and 350 g of ethyl acetate were added thereto,The organic phase was washed with a sodium carbonate solution,Washed with a saturated saline solution,After treatment with anhydrous sodium sulfate,filter,Concentration (-0. IMPa, below 45 C),A solid was obtained which was beaten with 102 g of n-heptane,filter,Dried to give 111.5 g of a compound of formula IV as a white solid,The yield was 90.8%Chemical purity 96. 3%Optical purity 99. 8%.
  • 14
  • [ 478646-28-5 ]
  • [ 124-63-0 ]
  • C15H23NO8S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
83.1% With triethylamine; In dichloromethane; at -5 - 0℃; In a dropping funnel,Thermometer in a dry three-necked flask,80 g of the compound of formula IV (n = 2)520 g of methylene chloride and adding 102.3 g of triethylamine,Stirring and cooling to -5 ~ 0 C,At this temperature, 97.6 g of methanesulfonyl chloride was added dropwise104 g of methylene chloride,After the reaction of raw materials,280 g of water was added,Heated to 15 ~ 25 C layered,The organic layer was washed with saturated brine,The organic phase was distilled under reduced pressure (below 40 C, -0.09 MPa) to give a yellow oil,Cooling to 15 ~ 20 C by adding 128g of ethanol,Cooled to -10 ~ -5 C crystallization,To obtain 107 as a white solid of formula III. 5 g,The yield was 83.1%Chemical purity 98.7%Optical purity 99. 9%.
 

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