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Chemical Structure| 406913-93-7 Chemical Structure| 406913-93-7

Structure of 406913-93-7

Chemical Structure| 406913-93-7

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Product Details of [ 406913-93-7 ]

CAS No. :406913-93-7
Formula : C5H10O3
M.W : 118.13
SMILES Code : OC[C@@H]1OCCOC1
MDL No. :MFCD16652371
InChI Key :CMEPUAROFJSGJN-YFKPBYRVSA-N
Pubchem ID :44429359

Safety of [ 406913-93-7 ]

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

Computational Chemistry of [ 406913-93-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 27.37
TPSA ?

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

38.69 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.34
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

-0.91
Log Po/w (WLOGP)?

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

-0.61
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.

-1.04
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

0.75
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.09

Water Solubility

Log S (ESOL):?

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

0.07
Solubility 138.0 mg/ml ; 1.17 mol/l
Class?

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

Highly soluble
Log S (Ali)?

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

0.58
Solubility 450.0 mg/ml ; 3.81 mol/l
Class?

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

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

-0.02
Solubility 113.0 mg/ml ; 0.959 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.

-7.67 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

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)

2.75

Application In Synthesis of [ 406913-93-7 ]

* 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.

  • Upstream synthesis route of [ 406913-93-7 ]

[ 406913-93-7 ] Synthesis Path-Upstream   1~10

  • 1
  • [ 917882-63-4 ]
  • [ 406913-93-7 ]
YieldReaction ConditionsOperation in experiment
89% With palladium 10% on activated carbon; hydrogen In ethanol for 18 h; To a so[ution of Intermediate 83 (1 .25 g, 4.74 mmo[) in ethano[ (20 mL) was added pa[[adium, 10 percent on carbon (192 mg) and the reaction mixture stirred under an atmosphere of hydrogen for 18 h. The reaction mixture was fi[tered through a p[ugof Ce[ite®, washing with EtOAc, and concentrated under reduced pressure toafford 630 mg (89percent yie[d) of the tit[e compound as pa[e ye[[ow oi[.1H NMR (500 MHz, Ch[oroform-d): 6 [ppm] 3.85 - 3.67 (m, 5H), 3.66 - 3.57 (m, 2H),3.55 (dd, J = 11.7, 5.9 Hz, 1H), 3.46 (dd, J = 11.1, 10.0 Hz, 1H), 1.75 (5, 1H).
References: [1] Patent: WO2016/91776, 2016, A1, . Location in patent: Page/Page column 233.
[2] Patent: US2006/293358, 2006, A1, . Location in patent: Page/Page column 50.
[3] Patent: US2009/182002, 2009, A1, . Location in patent: Page/Page column 15.
[4] Journal of Medicinal Chemistry, 2011, vol. 54, # 12, p. 4092 - 4108.
  • 2
  • [ 934346-80-2 ]
  • [ 406913-93-7 ]
YieldReaction ConditionsOperation in experiment
20.8% With sodium hydroxide In tetrahydrofuran; water at 90℃; for 24 h; 2J (11.1 g, 81.3 mmol) was dissolved in 50 mL of THF. Sodium hydroxide (16.3 g, 406 mmol) in 50 mL of water was added and the reaction was heated in a 90 0C oil bath for one day. Despite the TLC showing the reaction to be only half completed the product was extracted from the aqueous layer with ethyl acetate/THF, dichloromethane, n-butanol. The first two extractions contained product and the starting material, which was later purified by flash <n="157"/>column (ethyl acetate/hexane 30/70). The latter extractions contained pure (S)-(1, 4-dioxan-2- yl)methanol (2K, 1.98 g, 20.8 percent yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.47 (t, 7=9.98 Hz, 1 H) 3.51 - 3.67 (m, 3 H) 3.67 - 3.87 (m, 5 H).
References: [1] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 7, p. 2667 - 2679.
[2] Patent: WO2009/97578, 2009, A1, . Location in patent: Page/Page column 155-156.
[3] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 13, p. 3207 - 3211.
  • 3
  • [ 27905-76-6 ]
  • [ 406913-93-7 ]
YieldReaction ConditionsOperation in experiment
30% With sodium hydroxide In water at 20 - 90℃; for 5 h; The product from step 1 (16.06 g, 92.81 mmol) and 1M NaOH (185 mL, 185 mmol) were mixed and the biphasic mixture stirred at RT. After 2.5 h the reaction mixture was heated to 90° C. degrees for 2.5 h then allowed to cool to RT and evaporated. The remaining slurry was washed with DCM/MeOH (95:5) three times, filtered and the filtrate was evaporated. The remaining 9.5 g of oil was purified by SiO2 chromatography (400 g SiO2) eluting with a MeOH/DCM gradient (0-4percent MeOH over 40 min) to afford a 30percent yield of [1,4]dioxan-2-yl-methanol (114a).
References: [1] Patent: US2008/249087, 2008, A1, . Location in patent: Page/Page column 35.
  • 4
  • [ 51594-55-9 ]
  • [ 107-07-3 ]
  • [ 406913-93-7 ]
YieldReaction ConditionsOperation in experiment
23 g
Stage #1: With boron trifluoride diethyl etherate In toluene at 30 - 38℃; for 0.333333 h;
Stage #2: With sodium hydroxide In water; toluene at 16 - 20℃; for 1 h;
A mixture of (R)-2-(chloromethyl)oxirane (55, 109 mL, 1.62 mol) and BF3.OEt2 (3.4 mL, 0.027 mol) in toluene (200 mL) was heated to an internal temperature of 30° C. and 2-choloroethanol (49 g, 0.53 mol) was added dropwise at a rate sufficient to main the reaction temperature at 36-38° C. The resulting mixture was aged at 36° C. for 20 min. The mixture was cooled to 16° C. and aqueous NaOH (250 mL, 23percent) was added with vigorous stirring over 1 h, maintaining the reaction temperature below 20° C. The mixture was aged for 1 h at rt. The two layers were separated, and the aqueous phase was extracted with toluene (130 mL). The combined organic layers were washed with water (100 mL), the resulting organic layer was distilled to low volume, monitoring the distillate for loss of product to give the final intermediate 56 (23 g).1H-NMR: (CDCl3): δ 3.33-3.84 (m, 9H).
References: [1] Patent: US2014/57927, 2014, A1, . Location in patent: Paragraph 0294; 0295.
  • 5
  • [ 861852-08-6 ]
  • [ 406913-93-7 ]
References: [1] Patent: WO2010/68863, 2010, A2, . Location in patent: Page/Page column 70.
  • 6
  • [ 934346-53-9 ]
  • [ 406913-93-7 ]
References: [1] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 7, p. 2667 - 2679.
[2] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 13, p. 3207 - 3211.
  • 7
  • [ 406913-89-1 ]
  • [ 406913-93-7 ]
References: [1] Enantiomer, 2001, vol. 6, # 5, p. 267 - 273.
  • 8
  • [ 29908-11-0 ]
  • [ 406913-93-7 ]
References: [1] Enantiomer, 2001, vol. 6, # 5, p. 267 - 273.
  • 9
  • [ 18371-74-9 ]
  • [ 406913-93-7 ]
References: [1] Enantiomer, 2001, vol. 6, # 5, p. 267 - 273.
  • 10
  • [ 406913-84-6 ]
  • [ 406913-93-7 ]
References: [1] Enantiomer, 2001, vol. 6, # 5, p. 267 - 273.
 

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