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Chemical Structure| 82962-54-7

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Product Details of [ 82962-54-7 ]

CAS No. :82962-54-7
Formula : C9H16O4
M.W : 188.22
SMILES Code : O=C(C1COC(C)(C)OC1)OCC
MDL No. :MFCD11975772
InChI Key :MYGMWHATZAFUIU-UHFFFAOYSA-N
Pubchem ID :11019611

Safety of [ 82962-54-7 ]

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

Computational Chemistry of [ 82962-54-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 0
Fraction Csp3 0.89
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 46.76
TPSA ?

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

44.76 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.53
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

0.64
Log Po/w (WLOGP)?

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

0.95
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

1.47
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.23

Water Solubility

Log S (ESOL):?

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

-1.21
Solubility 11.5 mg/ml ; 0.0614 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.

-1.16
Solubility 13.2 mg/ml ; 0.0699 mol/l
Class?

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

Very 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

-1.49
Solubility 6.15 mg/ml ; 0.0327 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

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.

-6.99 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)

2.67

Application In Synthesis of [ 82962-54-7 ]

* 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.

  • Downstream synthetic route of [ 82962-54-7 ]

[ 82962-54-7 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 82962-54-7 ]
  • [ 4728-12-5 ]
YieldReaction ConditionsOperation in experiment
96% With lithium aluminium tetrahydride; In diethyl ether; at 20℃; for 3h;Inert atmosphere; To a suspension of LiAihh (0.50 g . 13.2 mmol) in Epsilon2upsilon (30 ml) was added a solution of 18.4 (2.0? g . 1 1 mmoL) in E0 (30 ml.) dropwise under argon. The reaction mixture was stirred at r.t for 3 hr. The reaction was quenched with water (0.9 roU, filtered, and the filtrate was washed with E0 . The combined organic layers were dried and concentrated under reduced pressure to give 18.5 ( 1.56 g, 96percent) as a colorless oil. 1 H MR (400 MHz, DMSO~c delta 4.52 (i J=5.2H , 1 H), 3.81 (q, 2H), 3.60 (q, 2H), 3.38 (q, 2H). 1.70 (m, 1H), 1.29 (, 6H).
76% A solution of 2,2-dimethyl-[1,3]dioxane-5-carboxylic acid ethyl ester (7.03 g, 37.35 mmol) in tetrahydrofuran (20 ml) was added dropwise to a cooled to 0° C. suspension of lithium aluminum hydride (1.8 g, 48.55 mmol) in tetrahydrofuran (20 ml). The reaction was stirred at 0° C. for 20 min and at 25° C. for 2 h. After such time, ethyl acetate (1 ml) and a few crystals of sodium sulphate decahydrate were added with caution. After stirring at 25° C. for 1 h saturated sodium chloride solution was added and the product extracted with ethyl acetate (3.x.100 ml). The organics were washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo to afford (2,2-dimethyl-[1,3]dioxan-5-yl)-methanol (4.09 g, 76percent) as a clear oil: 1H NMR (300 MHz, CDCl3) delta ppm 1.39 (s, 3 H, CH3), 1.44 (s, 3 H, CH3), 1.79-1.90 (m, 1 H, CH), 2.15-2.26 (brs, 1 H, OH), 3.69-3.81 (m, 2 H, 2.x.OCH of 2.x.OCH2), 3.74 (d, J=6.8 Hz, 2 H, OCH2), 3.96-4.05 (m, 2 H, 2.x.OCH of 2.x.OCH2).
75.2% With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 2.33333h;Inert atmosphere; Under nitrogen, to a solution of LiAlH4 (1.39 g, 36.58 mmol) in THF (40 mL) which was cooled to 0° C., compound Ij?-1 (5.29 g, 28.0 mmol) (according to the synthesis procedure in the patent WO 2008/0021032) was added dropwise. The mixture was stirred for 20 minutes at 0° C. and 2 hours at room temperature. When the reaction finished, the mixture was diluted with Et2O (30 mL). With an ice bath, H2O (0.14 mL) was added dropwise to the mixture, followed with NaOH solution (15percent, 0.14 mL) and H2O (0.42 mL) in sequence. After the mixture was stirred for 20 minutes at room temperature, appropriate amount of MgSO4 was added to it and then another 20 minutes for stirring proceeded. After filtration, the filtrate was concentrated under vacuum to afford compound Ii?-1 (3.1 g, 75.2percent). [0138] 1HNMR (500MHz, CDCl3) delta: 3.93-3.96 (m, 2H), 3.65-3.72 (m, 4H), 1.73-1.79 (m, 1H), 1.35(d, J=25.0 HZ, 6H).
75.2% With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 2.33333h;Inert atmosphere; Example 7: Preparation of compound Ii"-1: [0094] Under nitrogen, to a solution of LiAlH4 (1.39 g, 36.58 mmol) in THF (40 mL) which was cooled to 0°C, compoundIj"-1 (5.29 g, 28.0 mmol) (according to the synthesis procedure in the patent WO 2008/0021032) was added dropwise.The mixture was stirred for 20 minutes at 0°C and 2 hours at room temperature. When the reaction finished, the mixturewas diluted with Et2O (30 mL). With an ice bath, H2O (0.14 mL) was added dropwise to the mixture, followed with NaOHsolution (15percent, 0.14 mL) and H2O (0.42 mL) in sequence. After the mixture was stirred for 20 minutes at room temperature,appropriate amount of MgSO4 was added to it and then another 20 minutes for stirring proceeded. After filtration, thefiltrate was concentrated under vacuum to afford compound Ii"-1 (3.1 g, 75.2percent).1HNMR (500MHz, CDCl3) delta: 3.93-3.96 (m, 2H), 3.65-3.72 (m, 4H), 1.73-1.79 (m, 1H), 1.35 (d, J=25.0HZ, 6H).
58% With lithium aluminium tetrahydride; In tetrahydrofuran; for 2h;Inert atmosphere; Reflux; LiAlH4 (60 g, 1.58 mol) was suspended in dry THF (500 mL) under inert atmosphere. The solution of 3 (188 g,1 mol) in THF (600 mL) was added dropwise and the mixture was refluxed for 2 hours. The mixture was quenched by 6M NaOH solution upon cooling and filtered; the precipitate was washed by ethyl acetate (300 mL). The solvents were evaporated and the residual oil was distilled yielding S3 (85 g, 58percent) as colorless liquid 1. 1H NMR (700 MHz, CDCl3, 300K): delta = 4.02 (dd, J = 4.3 Hz, 12.2 Hz, 2 H), 3.78 (dd, J = 5.8 Hz,12.2 Hz, 2 H), 3.76 (dd, J = 5.1 Hz, 6.6 Hz, 2 H), 1.83-1.87 (m, 1H), 1.66 (t, J = 5.1 Hz, 1 H),1.45 (s, 3 H), 1.41 (s, 3 H).
With sodium hydroxide; In water; EXAMPLE 4 2,2-Dimethyl-5-Hydroxymethyl-1,3-Dioxane Lithium aluminum hydride (80 g) is stirred in ether (2000 ml) while the product of Example 3 (230 g) in ether (250 ml) is added dropwise. When the addition is complete the mixture is stirred an additional 16 hours. The reaction mixture is decomposed by careful addition of water (80 ml) followed by 15percent aqueous sodium hydroxide (80 ml) and additional water (240 ml). The resulting suspension is filtered, the filter cake washed with ethanol and ether and the combined filtrates evaporated to give a residue. Distillation of the residue gives the title product (155 g) (81percent) B.P. 75° C. (0.05 mm).

 

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