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Chemical Structure| 23579-92-2 Chemical Structure| 23579-92-2

Structure of 23579-92-2

Chemical Structure| 23579-92-2

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Product Details of [ 23579-92-2 ]

CAS No. :23579-92-2
Formula : C7H9NO
M.W : 123.15
SMILES Code : C1=C(N=CC=C1)COC
English Name :2-(Methoxymethyl)pyridine
MDL No. :MFCD00030825
InChI Key :QDTSINVSGKAPBV-UHFFFAOYSA-N
Pubchem ID :253220

Safety of [ 23579-92-2 ]

Computational Chemistry of [ 23579-92-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.29
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 35.1
TPSA ?

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

22.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.64
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

0.6
Log Po/w (WLOGP)?

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

1.08
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.

0.22
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

1.67
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.04

Water Solubility

Log S (ESOL):?

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

-1.34
Solubility 5.59 mg/ml ; 0.0454 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.

-0.64
Solubility 28.3 mg/ml ; 0.23 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

-2.51
Solubility 0.379 mg/ml ; 0.00308 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.

-6.63 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)

1.38

Application In Synthesis of [ 23579-92-2 ]

* 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 [ 23579-92-2 ]

[ 23579-92-2 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 23579-92-2 ]
  • [ 403-29-2 ]
  • [ 88274-04-8 ]
YieldReaction ConditionsOperation in experiment
78.4% In acetone for 20h; Heating;
  • 2
  • [ 23579-92-2 ]
  • [ CAS Unavailable ]
  • [ 333735-06-1 ]
YieldReaction ConditionsOperation in experiment
With zinc In methanol; propan-1-ol for 4h; Heating / reflux; 3 EXAMPLE 3 EXAMPLE 3; This example describes synthesis of an additional mid-transition metal complex 5 of the invention as illustrated in Scheme 5: A 2:5 molar ratio of MoCl3 to 2-(methoxymethyl)-pyridine is dissolved in a methanol/1-propanol solution. A dash of Zn dust is added and the solution heated to 100° C. and allowed to reflux for 4 hours. The reagents and procedures of Example 1, part (b), are then used to yield the desired metal complex 5.
  • 3
  • [ 23579-92-2 ]
  • [ 78-95-5 ]
  • [ 610766-99-9 ]
YieldReaction ConditionsOperation in experiment
77.5% Stage #1: 2-(methoxymethyl)pyridine; chloroacetone With potassium carbonate; lithium bromide In acetonitrile Heating / reflux; Stage #2: With potassium carbonate In water; acetonitrile III The compounds of formula II, when R1 represents a radical -OCH3 or a radical -OCH2C6H5, are also prepared using the Tschitschibabin reaction according to the following synthesis schemes:; Preparation III Synthesis of 1-methoxy-2-methylindolizine This compound is obtained starting with 2-(methoxymethyl)pyridine and chloroacetone, using the Tschitschibabin reaction. The product is isolated in the form of a yellow oil which crystallizes in the freezer. Yield: 77.5% Mass spectrometry (ES+ mode): MH+=161.8
  • 4
  • [ 6959-47-3 ]
  • [ 23579-92-2 ]
YieldReaction ConditionsOperation in experiment
With sodium methoxide; natrium In methanol; lithium hydroxide monohydrate 1 EXAMPLE 1 EXAMPLE 1 2-(Chloromethyl)pyridine hydrochloride (16.3 g., 0.1 mole) is dissolved in 100 ml. of methanol. Freshly prepared sodium methoxide (5 g., 0.22 mole of sodium dissolved in 150 ml. of methanol) is added dropwise. The resulting mixture is heated at reflux for 18 hours, then filtered. The filtrate is concentrated. Water and ether are added, the aqueous phase is extracted with ether and the combined ethereal phases are washed with water and saturated aqueous sodium chloride, then dried over magnesium sulfate, concentrated and distilled to give 2-(methoxymethyl)pyridine.
Multi-step reaction with 2 steps 1: Sodium hydrogenocarbonate / dichloromethane; lithium hydroxide monohydrate / Inert atmosphere 2: methanol / 19 h / 75 °C / Inert atmosphere
  • 5
  • [ 4377-33-7 ]
  • [ 23579-92-2 ]
YieldReaction ConditionsOperation in experiment
With sodium methylate 1 EXAMPLE 1 Alternatively, 0.1 mole of 2-(chloromethyl)pyridine and 0.11 mole of sodium methoxide are used in the above procedure to give 2-(methoxymethyl)pyridine. Also, 2-(methoxymethyl)pyridine is prepared by the following alternative procedure.
  • 6
  • [ 586-98-1 ]
  • [ 74-88-4 ]
  • [ 23579-92-2 ]
YieldReaction ConditionsOperation in experiment
In water; dimethyl sulfoxide 1 EXAMPLE 1 A mixture of 10.9 g. of 2-pyridinemethanol and 2.4 g. of sodium hydride in 50 ml. of dimethylsulfoxide is warmed on a steam bath for 15 minutes, then cooled to room temperature. Methyl iodide (14.2 g.) is added and then the mixture is heated at 40°C. for 1 hour. Water (150 ml.) is then added and the mixture is extracted with ether. The extracts are dried, concentrated and distilled to give 2-(methoxymethyl)pyridine.
  • 7
  • [ 23579-92-2 ]
  • [ 16420-13-6 ]
  • [ 52443-71-7 ]
YieldReaction ConditionsOperation in experiment
With phenyllithium In water; benzene 24 EXAMPLE 24 EXAMPLE 24 Alternatively, 2-methoxy-N,N-dimethyl-2-(2-pyridyl)thioacetamide is prepared by the following procedures. To 0.10 mole of phenyl lithium in 100 ml. of benzene/ether at 0°C. is added dropwise 10.6 g. (0.084 mole) of 2-(methoxymethyl)pyridine dissolved in 75 ml. of benzene. To this mixture is added dropwise 10.0 g. (0.081 mole) of N,N-dimethylthiocarbamoyl chloride in 100 ml. of benzene. The resulting mixture is stirred at room temperature overnight, then poured into 100 ml. of water and acidified. The organic phase is extracted once with dilute aqueous acid. The combined aqueous phases are extracted twice with ether, then made basic to about pH 10 and extracted three times with chloroform. The combined chloroform extracts are dried over magnesium sulfate and the solvent is removed by evaporation. The residue is chromatographed, then distilled in vacuo to give 2-methoxy-N,N-dimethyl-2-(2-pyridyl)thioacetamide.
  • 8
  • [ 23579-92-2 ]
  • [ CAS Unavailable ]
  • [ 57-06-7 ]
  • [ 52443-75-1 ]
YieldReaction ConditionsOperation in experiment
With phenyllithium In water; benzene 4 EXAMPLE 4 EXAMPLE 4 A solution of 9.95 g. (0.081 mole) of 2-(methoxymethyl)pyridine in 80 ml. of dry benzene is added dropwise to a chilled solution of 40 ml. (0.084 mole) of phenyl lithium in 80 ml. of dry benzene. The mixture is stirred at 0°C. for 1 hour after the addition is complete. Then 8.02 g. of allyl isothiocyanate in 50 ml. of benzene is added dropwise and the mixture is allowed to come to room temperature gradually. The mixture is then diluted with 500 ml. of water and acidified with 10% hydrochloric fractions The layers are separated and the organic layer is washed several times with water. The aqueous layers are combined, neutralized with 10% aqueous sodium hydroxide solution and then brought to pH 9 5% aqueous sodium bicarbonate solution, then extracted with chloroform. The chloroform extracts are washed once with brine and dried over magnesium sulfate. The solvent is removed and the residue is chromatographed on a silica gel column, eluding with ethyl acetate. The fraction, containing the product are combined and evaporated and the residue is recrystallized from ethyl acetate/hexane to give N-allyl-2-methoxy-2-(2-pyridyl)thioacetamide, m.p. 59.5°-60°C.
  • 9
  • [ 23579-92-2 ]
  • [ 103-72-0 ]
  • [ 52443-69-3 ]
YieldReaction ConditionsOperation in experiment
With phenyllithium In hexane; water; ethyl acetate; benzene 15 EXAMPLE 15 EXAMPLE 15 2-(Methoxymethyl)pyridine (1.85 g., 0.015 mole) in 15 ml. of dry benzene is added dropwise to a chilled solution of phenyl lithium (8.1 ml. of 2.1 molar solution, 0.017 mole) in 15 ml. of dry benzene. After the addition is complete, the mixture is stirred at 0°C. for 1 hour. Phenyl isothiocyanate (2.03 g., 0.015 mole) in 15 ml. of dry benzene is added dropwise and the mixture is allowed to come to room temperature gradually, then the mixture is stirred overnight. The mixture is diluted with 50 ml. of water and acidified with dilute hydrochloric acid. The layers are separated and the organic layer is washed several times with water. The aqueous layers are combined, basified with dilute aqueous sodium hydroxide solution and extracted several times with chloroform. The chloroform extracts are combined, washed once with brine and dried over magnesium sulfate. The solvent is removed under reduced pressure to give an oil which is placed on a silica gel "dry-column", eluding with ethyl acetate to give, after cooling and recrystallizing from ethyl acetate/hexane, 2-methoxy-N-phenyl-2-(2-pyridyl)-thioacetamide, m.p. 97°-98.5°C.
  • 10
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
  • [ 23579-92-2 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; methanol for 0.833333h; 109.a To a solution of SMOPS (4.8 g, 0.028 mol) in DMSO (dry, 50 mL) was added 2- bromomethyl pyridine HBr (5 g, 0.019 mol) at r.t.. After 40 min pH of the solution was adjusted to 8 by the addition of aqueous bicarbonate solution. The reaction mixture was extracted with EtOAc (4 x 100 mL), the organic layers were combined, dried over anhydrous sodium sulphate, filtered and the solvents were removed in vacuo. The residue was redissolved in a mixture of solvents consisting of THF (200 mL) and methanol (10 mL) and treated with a solution of sodium methoxide (4 mL, 25%) over a period of 10 min. After stirring for 40 min, the reaction mixture was concentrated in vacuo and dissolved in water (20 mL). Followed by addition of a solution of hydroxylamine-O- sulfonic acid (12.66 g, 0.099 mol), sodium acetate (7g) in water (60 mL) followed by stirring at r.t.. After 48 h pH of the solution was adjusted to 9 by the addition of aqueous bicarbonate solution and the mixture subjected to freeze drying. The solid thus obtained was treated with methanol, methanolic layer separated and concentrated. The residue was purified by flash chromatography on silica using a gradient of EtOAc in pet ether followed by EtOAc and then with MeOH in EtOAc to give l-Pyridin-2-ylmethanesulfonamide. Yield: 400 mg (12 %). EPO 1H NMR (400 MHz, DMSO-d6) δ 4.42-4.45 (2H, m), 6.90-6.95 (2H, m), 7.33-7.39 (IH, m), 7.45-7.50(1H3 m), 7.78-7.85 (IH, m), 8.53-8.59 (IH, m) MS m/z: 173 (M+l).
  • 11
  • [ 23579-92-2 ]
  • [ 61017-18-3 ]
  • [ 889954-95-4 ]
YieldReaction ConditionsOperation in experiment
With sodium acetate In water at 20℃; for 48h; 109.a To a solution of SMOPS (4.8 g, 0.028 mol) in DMSO (dry, 50 mL) was added 2- bromomethyl pyridine HBr (5 g, 0.019 mol) at r.t.. After 40 min pH of the solution was adjusted to 8 by the addition of aqueous bicarbonate solution. The reaction mixture was extracted with EtOAc (4 x 100 mL), the organic layers were combined, dried over anhydrous sodium sulphate, filtered and the solvents were removed in vacuo. The residue was redissolved in a mixture of solvents consisting of THF (200 mL) and methanol (10 mL) and treated with a solution of sodium methoxide (4 mL, 25%) over a period of 10 min. After stirring for 40 min, the reaction mixture was concentrated in vacuo and dissolved in water (20 mL). Followed by addition of a solution of hydroxylamine-O- sulfonic acid (12.66 g, 0.099 mol), sodium acetate (7g) in water (60 mL) followed by stirring at r.t.. After 48 h pH of the solution was adjusted to 9 by the addition of aqueous bicarbonate solution and the mixture subjected to freeze drying. The solid thus obtained was treated with methanol, methanolic layer separated and concentrated. The residue was purified by flash chromatography on silica using a gradient of EtOAc in pet ether followed by EtOAc and then with MeOH in EtOAc to give l-Pyridin-2-ylmethanesulfonamide. Yield: 400 mg (12 %). EPO 1H NMR (400 MHz, DMSO-d6) δ 4.42-4.45 (2H, m), 6.90-6.95 (2H, m), 7.33-7.39 (IH, m), 7.45-7.50(1H3 m), 7.78-7.85 (IH, m), 8.53-8.59 (IH, m) MS m/z: 173 (M+l).
  • 12
  • [ 23579-92-2 ]
  • [ 106-54-7 ]
  • [ 353258-69-2 ]
YieldReaction ConditionsOperation in experiment
75% With di-tert-butyl peroxide In neat (no solvent) at 120℃; for 24h; Sealed tube;
  • 13
  • [ 23579-92-2 ]
  • [ 586-77-6 ]
  • [ 1878988-72-7 ]
YieldReaction ConditionsOperation in experiment
83% With palladium diacetate; sodium hexamethyldisilazane; nixantphos In 1,2-dimethoxyethane at 20℃; for 12h; chemoselective reaction;
  • 14
  • [ 23579-92-2 ]
  • [ 586-77-6 ]
  • [ 1878988-90-9 ]
YieldReaction ConditionsOperation in experiment
72% With palladium diacetate; Lithium 1,1,1,3,3,3-hexamethyldisilazide; nixantphos at 45℃; for 24h; chemoselective reaction;
 

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