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Chemical Structure| 3143-02-0 Chemical Structure| 3143-02-0

Structure of 3143-02-0

Chemical Structure| 3143-02-0

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Product Details of [ 3143-02-0 ]

CAS No. :3143-02-0
Formula : C5H10O2
M.W : 102.13
SMILES Code : C(C1(COC1)C)O
MDL No. :MFCD00010273
InChI Key :NLQMSBJFLQPLIJ-UHFFFAOYSA-N
Pubchem ID :137837

Safety of [ 3143-02-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H317
Precautionary Statements:P280

Computational Chemistry of [ 3143-02-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 26.02
TPSA ?

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

29.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.42
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

-0.18
Log Po/w (WLOGP)?

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

0.02
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.

-0.16
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

1.1
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.44

Water Solubility

Log S (ESOL):?

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

-0.29
Solubility 51.9 mg/ml ; 0.508 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.

0.02
Solubility 106.0 mg/ml ; 1.04 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

-0.58
Solubility 26.8 mg/ml ; 0.262 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.

-7.05 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)

1.19

Application In Synthesis of [ 3143-02-0 ]

* 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 [ 3143-02-0 ]

[ 3143-02-0 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 3143-02-0 ]
  • [ 78385-26-9 ]
YieldReaction ConditionsOperation in experiment
95% With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 0 - 20℃; for 0.333333h;Product distribution / selectivity; 10 ml (0.1 mol) of 3-methyl-3-(hydroxymethyl)oxetane and 36.58 g (0.11 mol) of carbone tetrabromide were dissolved in 100 ml of CH2Cl2. The solution was cooled to 0C under nitrogen atmosphere, and 31.56 g (0.12 mol) of triphenylphosphine was gradually added thereto. The mixture was heated to room temperature and stirred for 20 minutes. After the reaction terminated, the solvent was removed under reduced pressure. 100 ml of ethylene acetate was added thereto and the mixture was filtered using celite to remove impurities. After the solvent was removed from the mixture, hexane was added thereto. The mixture was filtered using celite, and concentrated under reduced pressure. The resultant product was fractionally distilled to obtain 16 g of 3-methyl-3-(bromomethyl)oxetane (Yield: 95%). NMR spectroscopy of the resulting product was: 1H NMR (CDCl3, 300MHz): delta4.46-4.38 (d+d, 4H), 3.65(s, 2H), 1.44(s, 3H).
With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 0 - 23℃; for 1.33333h; 3-Bromomethyl-3-methyl-oxetane; To a dichloromethane (600 ml) solution of (3-Methyl-oxetan-3-yl)-methanol (50 g, 0.4896 mol, prepared as in Corey, E. J., Raju, N., Tetrahedron Lett., 1983, 5571) at about 0 C. was added carbon tetrabromide (165.35 g, 0.4986 mol) followed by the addition of triphenyl phosphine (179 g, 0.683 mol) slowly in portions over about 20 minutes. The reaction was allowed to warm to about 23 C. and was stirred at that temperature for about 1 hour then was concentrated in vacuo. The residue was diluted with diethyl ether and cooled to about 0 C., then was filtered through Celite and the organic layer was concentrated in vacuo. The residue was then diluted with hexanes and filtered then concentrated in vacuo and distilled under vacuum to give 124.3 g of 3-bromomethyl-3-methyl-oxetane as a colorless oil.
  • 3
  • [ 3143-02-0 ]
  • [ 558-13-4 ]
  • [ 603-35-0 ]
  • [ 78385-26-9 ]
  • NHCH3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; 3-Bromomethyl-3-methyl-oxetane To a dichloromethane (600 ml) solution of (3-Methyl-oxetan-3-yl)-methanol (50 g, 0.4896 mol, prepared as in Corey, E.J., Raju, N., Tetrahedron Lett.,1983, 5571) at about 0C was added carbon tetrabromide (165.35 g, 0.4986 mol) followed by the addition of triphenyl phosphine (179 g, 0.683 mol) slowly in portions over about 20 minutes. The reaction was allowed to warm to about 23C and was stirred at that temperature for about 1 hour then was concentrated in vacuo.The residue was diluted with diethyl ether and cooled to about 0C, then was filtered through Celite and the organic layer was concentrated in vacuo.Theresidue was then diluted with hexanes and filtered then concentrated in vacuoand distilled under vacuum to give 124.3 g of 3-bromomethyl-3-methyl-oxetane as a colorless oil.
  • 4
  • [ 3143-02-0 ]
  • [ 2491-15-8 ]
  • [ 1159414-65-9 ]
  • 5
  • [ 3143-02-0 ]
  • [ 33332-28-4 ]
  • [ 1431654-81-7 ]
YieldReaction ConditionsOperation in experiment
100% NaH (60percent in oil, 1.24 g, 30.9 mmol) was washed twice with pentane and dried under vacuum. Dioxane (50 mL) was added, followed by (3-methyloxetan-3-yl)methanol (3.0 mL, 30.9 mmol) dropwise. This was allowed to stir 2 h at room temp before addition of 6-chloropyrazin-2-amine (2.0 g, 15.4 mmol). The reaction was heated to reflux for 16 h, cooled and concentrated. Water was added (50 mL), and the mixture was extracted with EtOAc (3x75 mL), and the combined organics were washed with water and brine, dried with Na2SO4, filtered and concentrated. The crude product was purified by silica gel column chromatography (0-10percent MeOH/CH2 ) to give 6-((3-methyloxetan-3- yl)methoxy)pyrazin-2-amine (3.02 g, quant). MS (ESI) calcd for C9H13N3O2: 195.10; found: 196 [M+H]
100% NaH (60percent in oil, 1.24 g, 30.9 mmol) was washed twice with pentane and dried under vacuum. Dioxane (50 mL) was added, followed by (3-methyloxetan-3-yl)methanol (3.0 mL, 30.9 mmol) dropwise. This was allowed to stir 2 h at room temp before addition of 6-chloropyrazin-2-amine (2.0 g, 15.4 mmol). The reaction was heated to reflux for 16 h, cooled and concentrated. Water was added (50 mL), and the mixture was extracted with EtOAc (3x75 mL), and the combined organics were washed with water and brine, dried with Na2SO4, filtered and concentrated. The crude product was purified by silica gel column chromatography (0-10percent MeOH/CH2Cl2) to give 6-((3-methyloxetan-3-yl)methoxy)pyrazin-2-amine (3.02 g, quant.). MS (ESI) calcd for C9H13N3O2: 195.10; found: 196 [M+H].
 

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Technical Information

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