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Structure of 16830-24-3

Chemical Structure| 16830-24-3

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Product Details of [ 16830-24-3 ]

CAS No. :16830-24-3
Formula : C8H9NO2
M.W : 151.16
SMILES Code : COC(=O)C1=CC(C)=NC=C1
MDL No. :MFCD09991707
InChI Key :HHUNWJWOJPWLNK-UHFFFAOYSA-N
Pubchem ID :11542811

Safety of [ 16830-24-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 16830-24-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 40.48
TPSA ?

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

39.19 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.91
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

0.95
Log Po/w (WLOGP)?

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

1.18
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.

0.66
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

1.64
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.27

Water Solubility

Log S (ESOL):?

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

-1.65
Solubility 3.4 mg/ml ; 0.0225 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.

-1.36
Solubility 6.6 mg/ml ; 0.0437 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

-2.47
Solubility 0.512 mg/ml ; 0.00339 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.

-6.55 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)

1.39

Application In Synthesis of [ 16830-24-3 ]

* 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 [ 16830-24-3 ]

[ 16830-24-3 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 16830-24-3 ]
  • [ 105250-16-6 ]
YieldReaction ConditionsOperation in experiment
47% With lithium aluminium tetrahydride; In tetrahydrofuran; at -78℃; for 2h;Inert atmosphere; Cooling with acetone-dry ice; Ester S5 (0.120 g, 0.778 mmol) was placed in an oven dried 20 ml vial. The vialwas sealed under nitrogen, then anhydrous THF (6.0 mL) was added. LAH (0.031g, 0.817 mmol) was added to a separateoven dried 20 mL reaction vial. The vial was capped and purged with nitrogen before anhydrous THF (10.0 mL) was added.The solution was cooled to -78 C using a dry ice and acetone bath, then the ester solution was added dropwise via syringeover 5 min. The reaction was stirred at -78 C for 2 h. A sample aliquot was taken from the reaction, dissolved in 1 mLHPLC grade MeCN, and analyzed with LC-MS to confirm the completion of the reaction. The reaction was warmed to 0C, then was diluted with ether before a saturated sodium sulfate solution was added to quench the reaction. The mixturewas stirred for 15 min. before being vacuum filtered and condensed to yield the title compound as a light yellow oil (0.041g, 47%). 1H NMR showed the crude compound to be of sufficient purity to advance without further purification. Thiscompound has been previously reported and characterized (CAS 105250-16-6). 1H NMR (300 MHz, CD3OD) delta = 2.51(s, 3H), 4.63 (s, 3H) 7.21 (d, J = 5.3 Hz, 1H) 7.28 (s, 1H) 8.32 (d, J = 5.3 Hz, 1H).
38% In water; A solution of methyl 2-methyl-pyridine-4-carboxylate (800 mg, 6 mmol) in ether (5 ml) was added to lithium aluminium hydride (340 mg, 9 mmol) in ether (10 ml) cooled to 5 C. and the mixture stirred for 2 hours. Water was added, the mixture was filtered through diatomaceous earth and the pad was washed through with ethyl acetate. The filtrate was extracted with ethyl acetate and the combined extracts were washed with brine, dried (MgSO4) and the solvent removed by evaporation to give 4-hydroxymethyl-2-methylpyridine (240 mg, 38%) as a yellow oil. 1H NMR Spectrum: (CDCl3) 2.48(s, 3H); 5.44(s, 2H); 7.00(d, 1H); 7.10(s, 1H); 8.40(d, 1H) MS - ESI: 124 [MH]+
A solution of 2-methyl-isonicotinic acid methyl ester (58.41 g, 384 mmol) in THF (750 mL) was cooled to -78 C. Lithium aluminum hydride (2 M in THF, 21 1.5 mL, 423 mmol) was added dropwise over 1 hour, and the reaction was slowly warmed to room temperature over 2 hours. The reaction was diluted with Et20 (2 L) and cooled to 0 C. H20 (16 mL) was added slowly, followed by 15% aqueous NaOH (16 mL), and then additional H20 (48 mL), and the mixture was stirred for 3 hours at room temperature. MgS04 was then added and the mixture was stirred for another 1 hour, then filtered and concentrated to give the title compound
  • 2
  • [ 16830-24-3 ]
  • [ 7732-18-5 ]
  • [ 105250-16-6 ]
YieldReaction ConditionsOperation in experiment
67% With sodium hydroxide; In acetonitrile; A. Preparation of 4-Hydroxymethyl-2-methylpyridine STR240 To a suspension of 95% lithium aluminum hydride (2.4 g, 0.06 mol) in 150 mL of anhydrous ether was added a solution of methyl 2-methylisonicotinate1 (14.0 g, 0.093 mol) in 50 mL of anhydrous ether, at -5 C. under N2. The resulting mixture was stirred at room temperature for 30 min and was then refluxed for 2 h. An additional 1.2 g (0.03 mole) of lithium aluminum hydride was added portionwise and refluxing was continued for 1 h. The reaction mixture was then cooled at 0 C. and treated successively with 3.75 mL H2 O, 3.75 mL 15% aqueous NaOH and finally 11.25 mL of H2 O. This suspension was then filtered and the filter cake was washed with ether and then ethyl acetate. The filtrate was evaporated to give a dark yellow oil which was taken up in acetonitrile and then filtered through a pad of silica gel (elution with acetonitrile and then acetone). This gave the product (7.7 g, 67%) as a yellow oil: 1 Hnmr (CDCl3) delta8.30, 7.10 (ABq, J=5 Hz, 2H), 7.17 (s, 1H), 5.42 (s, --OH), 4.70 (s, CH2), 2.50 (s, CH3).
 

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Technical Information

Categories

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