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Chemical Structure| 109205-68-7 Chemical Structure| 109205-68-7

Structure of 109205-68-7

Chemical Structure| 109205-68-7

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Product Details of [ 109205-68-7 ]

CAS No. :109205-68-7
Formula : C6H7NO2
M.W : 125.13
SMILES Code : O=C1C=CC(CO)=CN1
MDL No. :MFCD09839753
InChI Key :JLPOBAADYFDVAV-UHFFFAOYSA-N
Pubchem ID :12018576

Safety of [ 109205-68-7 ]

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

Computational Chemistry of [ 109205-68-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 33.19
TPSA ?

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

53.09 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.09
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

-1.13
Log Po/w (WLOGP)?

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

-0.28
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.

-0.29
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

1.36
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.15

Water Solubility

Log S (ESOL):?

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

-0.33
Solubility 58.4 mg/ml ; 0.466 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.

0.51
Solubility 402.0 mg/ml ; 3.21 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

-1.72
Solubility 2.39 mg/ml ; 0.0191 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.

-7.87 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)

1.32

Application In Synthesis of [ 109205-68-7 ]

* 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 [ 109205-68-7 ]

[ 109205-68-7 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 66171-50-4 ]
  • [ 109205-68-7 ]
YieldReaction ConditionsOperation in experiment
With LiAlH4; In tetrahydrofuran; ethanol; water; ethyl acetate; To a suspension of LiAlH4 (0.32 gm, 8.4 mmol) in 80 ml THF was added, slowly and dropwise, a solution of methyl 6-hydroxynicotinate (1.15 gm, 7.5 mmol) in 400 ml THF. The mixture was stirred at room temperature for 1.5 hours and then refluxed for 10 minutes. The mixture was then cooled and the reaction quenched with 3.0 ml of ethyl acetate and 1.5 ml of water. The solvents were removed and the residue was taken up in 40 ml of refluxing ethanol. The solution was filtered through celite and ethanol was evaporated in vacuo. The product was purified by silica gel chromatography using ethyl acetate/methanol (2:1) as the eluent. The product 5-hydroxymethyl-2-pyridone was crystallized from ethanol/ethyl acetate and the yield of the reaction was 0.65 gm (80%). HRMS: m/e, M+ found 125.0468, 100%. Calc. for C6H7NO2: 125.0477, -6 ppm. 1H NMR (d6-DMSO): 11.47 (broad, 1H, NH), 7.39 (dd, J3-4=9.5 Hz, J4-6=2.5 Hz, 1H, C(4) H), 7.23 (d, J4-6=2.5 Hz, 1H, C(6)H), 6.27 (d, J3-4=9.5 Hz, 1H, C(3)H), 5.10 (t, J=5.5 Hz, 1H, CH2OH), 4.17 (d, J=5.5 Hz, 2H, CH2OH). IR (cm-1): 3271 (m, broad), upsilon(O-H); 3124 (m, broad), upsilon(N-H); 3011(m), upsilon(C-H); 1661(vs), upsilon(C=O).
  • 2
  • [ 109205-68-7 ]
  • 5-bromomethyl-2-pyridone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogen bromide; To <strong>[109205-68-7]5-hydroxymethyl-2-pyridone</strong> (114.9 mg, 0.9 mmol) was added 3.0 ml of 48% hydrobromic acid. The mixture was heated at 100 C. for 20 minutes. The excess hydrobromic acid was then evaporated in vacuo to give the corresponding 5-bromomethyl-2-pyridone. This compound was used without purification. HRMS: m/e, M+ found; 186.9626, 7.4% Calc. for C6H6BrNO: 186.9633, -3.9 ppm. The 5-bromomethyl-2-pyridone was taken up in diethyl amine and the solution refluxed for 1 hour.
  • 3
  • [ 109205-68-7 ]
  • [ 70258-18-3 ]
YieldReaction ConditionsOperation in experiment
With phosphorus pentachloride; sodium carbonate; trichlorophosphate; In ethyl acetate; STR18 2.0 g (0.016 mol) of 5-hydroxymethyl-2-pyridinone are added to a mixture of 6.7 g (0.032 mol) of phosphorus pentachloride and 2.5 g (0.016 mol) of phosphorus oxychloride, the mixture is stirred at reflux temperature for 7 hours, cooled and taken up in ethyl acetate, ice water is then added, the mixture is rendered neutral using sodium carbonate, the organic phase is separated off and dried over magnesium sulphate, and the solvent is removed under reduced pressure. The residue may be purified by distillation. 2.5 g (96% of theory) of 2-chloro-5-chloromethylpyridine of boiling point 70 C.-80 C. at 1 mbar are obtained.
  • 4
  • [ 106984-91-2 ]
  • [ 109205-68-7 ]
YieldReaction ConditionsOperation in experiment
With hydrogen;aluminum nickel; In ethanol; ethyl acetate; STR17 2 g of Raney nickel are added to 10.0 g (0.081 mol) of 2-pyridinone-5-aldehyde in 200 ml of ethanol, and the mixture is subsequently hydrogenated for 4 hours at 80 C. and 30 bar hydrogen pressure. For working up, the catalyst is filtered off, the filtrate is concentrated, and the solid which remains is purified by stirring with ethyl acetate, filtering off with suction and dried. 7 g (78% of theory) of 5-hydroxymethyl-2-pyridinone of melting point 130 C. are obtained.
  • 5
  • [ 66171-50-4 ]
  • [ 109205-68-7 ]
YieldReaction ConditionsOperation in experiment
To a suspension of methyl 6-oxo-1 ,6-dihydro-3-pyridinecarboxylate (400 mg; Fluorochem) in THF (7 mL) was added dropwise 2M lithium borohydride in THF (6.53 mL) and the reaction mixture was heated at 55 0C under an atmosphere of argon for 5 hr. The reaction mixture was allowed to cool to RT and MeOH (4 mL) and water (1 mL) were added carefully. The mixture was stirred at room temperature for 20 min and then concentrated under reduced pressure. The crude product was purified by column chromatography, Biotage SP4, 25+M column, 0 - 30% MeOH / DCM. The fractions containing product were combined and concentrated under reduced pressure to give the title compound (68 mg) as a white solid, m/z [M+H]+: 125.9. Retention time 0.24 min (LC/MS method 3).
  • 6
  • [ 109205-68-7 ]
  • C13H12BrNO5S [ No CAS ]
  • C17H13BrN2O5S [ No CAS ]
  • 7
  • [ 109205-68-7 ]
  • C13H12BrNO5S [ No CAS ]
  • C19H17BrN2O6S [ No CAS ]
YieldReaction ConditionsOperation in experiment
36% With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 30℃; To a solution of E2 (50 rng, 0.14 mrnol), 5(Iiydroxymethyi)pyridim2(1H}-one(20 mg, 0.16 mmol), and PPh3 (42 mg, 0.16 mmol) in TI-IF (2 mL) is added DIAD (54 mg,0.27 mmol) at room temperature. After stirring at 30 C overnight, the mixture isconcentrated. triturated with F:tOH (3 rnL), and collected by filtration to give 260 as a whitesolid (23 rng, 36% yield). (MS: [M±HI 481.1)
  • 8
  • [ 109205-68-7 ]
  • 2-chloro-6-(dimethylamino)-4-ethylpyridine-3,5-dicarbonitrile [ No CAS ]
  • 2-(dimethylamino)-4-ethyl-6-(((6-oxo-1,6-dihydropyridin-3-yl)methyl)thio)pyridine-3,5-dicarbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
41% 48% Hydrobromic acid (3 mL, 26.5 ymethyl)pyridin-2(1H)- one (400 mg, 3.20 mmol) at 0 C and then heated at 110 C for 16 hours. The mixture was concentrated to afford a crude black liquid (400 mg). To a solution of 2-chloro-6- (dimethylamino)-4-ethylpyridine-3,5-dicarbonitrile (synthesis described in example 3, step 3, 200 mg, 0.823 mmol) in N,N-dimethylformamide (10 mL) was added potassium thioacetate (188 mg, 1.646 mmol) and the reaction mixture was stirred at room temperature for 2 hours. After 2 hours the reaction mixture was cooled to 0 C, then potassium carbonate (228 mg, 1.646 mmol) and the crude black liquid (400 mg) were added and the mixture was stirred at room temperature for 1 hour. The reaction mass was diluted with ethyl acetate (100 mL) and washed with aqueous HCl solution (1 N, 2 x 100 mL). The organic layer was dried over anhydrous Na2SO4, filtered and the filtrate evaporated under vacuum to give crude compound. The crude compound was purified by silica gel column chromatography (100-200 mesh, eluted with 3-4% methanol in DCM) to afford 2-(dimethylamino)-4-ethyl-6- (((6-oxo-1,6-dihydropyridin-3-yl)methyl)thio)pyridine-3,5-dicarbonitrile (115 mg, 41%) as a brown solid. LCMS m/z = 340.1 [M+H]+.1H NMR (400 MHz, DMSO-d6) delta ppm 11.5 (s, 1H), 7.4 (dd, J = 2.4 Hz, J = 2.8 Hz, 1H), 7.4 (s, 1H), 6.2 (d, J = 9.2 Hz, 1H), 4.2 (s, 2H), 3.2- 3.4 (2s, 6H), 2.7 (q, J = 7.6 Hz, 2H), 1.2 (t, J = 7.6 Hz, 3H).
  • 9
  • [ 109205-68-7 ]
  • [ 1263413-99-5 ]
YieldReaction ConditionsOperation in experiment
93% With hydrogen bromide; In water; at 110℃; for 3h; 5-(Hydroxymethyl)-1,2-dihydropyridin-2-one (1.0 g, 7.991 mmol, 1.0 eq) in aqueous HBr (48%), was stirred at 110 C. for 3 h. After completion of the reaction (monitored by TLC, TLC system 5% MeOH in DCM, Rf-0.1), the solvent was removed under reduced pressure to get the crude product. The crude product was azeotroped with toluene to get 5-(bromomethyl)pyridin-2(1H)-one hydrobromide (2.0 g, 93%).
  • 10
  • [ 109205-68-7 ]
  • 5-((5-iodo-1H-indazol-1-yl)methyl)pyridin-2(1H)-one [ No CAS ]
  • 11
  • [ 109205-68-7 ]
  • 5-((5-iodo-1H-indazol-1-yl)methyl)-1-methylpyridin-2(1H)-one [ No CAS ]
 

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