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Chemical Structure| 13210-29-2

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1-(3-Hydroxypyridin-2-yl)ethanone

CAS No.: 13210-29-2

4.5 *For Research Use Only !

Cat. No.: A102278 Purity: 98%

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Product Details of [ 13210-29-2 ]

CAS No. :13210-29-2
Formula : C7H7NO2
M.W : 137.14
SMILES Code : CC(C1=NC=CC=C1O)=O
MDL No. :MFCD08062669
InChI Key :DYFSAZGSIBFUAI-UHFFFAOYSA-N
Pubchem ID :14088947

Safety of [ 13210-29-2 ]

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

Calculated chemistry of [ 13210-29-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 36.45
TPSA ?

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

50.19 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.66
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

1.07
Log Po/w (WLOGP)?

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

0.99
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.

-0.48
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

1.17
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.88

Water Solubility

Log S (ESOL):?

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

-1.74
Solubility 2.48 mg/ml ; 0.0181 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.

-1.72
Solubility 2.64 mg/ml ; 0.0193 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

-1.76
Solubility 2.41 mg/ml ; 0.0175 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.

-6.38 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)

1.27

Application In Synthesis [ 13210-29-2 ]

* 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.

  • Upstream synthesis route of [ 13210-29-2 ]

[ 13210-29-2 ] Synthesis Path-Upstream   1~13

  • 1
  • [ 13210-29-2 ]
  • [ 86467-39-2 ]
  • [ 83988-39-0 ]
References: [1] Heterocycles, 1987, vol. 26, # 11, p. 2921 - 2939.
  • 2
  • [ 13210-29-2 ]
  • [ 86467-39-2 ]
References: [1] Heterocycles, 1987, vol. 26, # 11, p. 2921 - 2939.
  • 3
  • [ 874-24-8 ]
  • [ 676-58-4 ]
  • [ 13210-29-2 ]
YieldReaction ConditionsOperation in experiment
77%
Stage #1: With triethylamine In tetrahydrofuran at 60 - 65℃; for 5 h;
Stage #2: With Methyl formate In tetrahydrofuran at 5 - 20℃;
Stage #3: With hydrogenchloride; water In tetrahydrofuran at 10℃;
Example 2; 3-methyl-N4[(1S)-3-methyl-1-([(4S,7R)-7-methyl-3-oxo-1-(2-pyridinylsulfonyl) hexahydro-1H-azepin-4-yl]amino}carbonyl)butyl]furo[3,2-b]pyridine-2-carboxamide; Preparation of 3-methylfuro[3,2-b]pyridine-2-carboxylic acid (6-1); Under nitrogen, charge the flask with 3 M methyl magnesium chloride in THF (600 mL, 1.80 mol, 5.0 equiv) and THF (500 mL). Heat the solution to 60-65° C. and add a solution of 3-hydroxypicolinic acid (1) (50 g, 0.36 mole), triethylamine (50 mL, 0.36 mole) in THF (250 mL) to the reaction mixture over approximately 3 h. Continue heating at reflux for 2 h. Cool the reaction to 5-10° C. and add methyl formate (44 mL) keeping the reaction temperature less than 20° C. At 10° C., add 10percent aqueous HCl to a pH 34. Transfer to separatory funnel and allow the layers to separate. Remove the top organic phase and extract the aqueous phase with THF (250 mL). Combine the organic phases combined and concentrate to 13-15 volumes and add water (170 mL). Continue with the vacuum distillation until all the THF has been removed. Cool the solution to 10° C., stir 0.5 h, filter and dry 1-(3-hydroxypyridin2-yl)ethanone (2) as the tan solid (38.1 g, 77percent yield).
References: [1] Patent: US2008/262224, 2008, A1, . Location in patent: Page/Page column 14-15.
  • 4
  • [ 917-64-6 ]
  • [ 63668-59-7 ]
  • [ 13210-29-2 ]
YieldReaction ConditionsOperation in experiment
65%
Stage #1: for 6.16667 h; Cooling with ice water bath; Reflux
Stage #2: With water; ammonium chloride In diethyl ether; benzeneCooling with ice water bath; Saturated solution
l-(3-Hydroxypyridin-2-yl)ethanone (50) A flame-dried 250 mL round bottom flask was charged with methylmagnesium iodide in ether (67.0 ml, 200 mmol). This solution was stirred in an ice-H2O bath as 2-cyanopyridin-3-yl acetate (49) (6.5 g, 40 mmol) in benzene (45 mL) was cannulated in over a period of 40 min. The resulting mixture was refluxed for 5.5 hrs, then cooled in an ice-H2O bath and cautiously quenched with <n="64"/>saturated NH4Cl aqueous solution. The aqueous layer was cautiously neutralized with 2N HCl aqueous solution and then extracted with EtOAc (2X). The combined organic layer was washed with brine (IX) and dried over anhydrous Na2SO4. Purification by combi- flash column chromatography (EtOAc/Hexanes) gave l-(3-hydroxypyridin-2-yl)ethanone (50) (3.6 g, 65percent yield) as a light yellow solid. 1H NMR (400 MHz, DMS0-d6) δ ppm 11.58 (1 H, s), 8.27 (1 H, dd, J=4.3, 1.6 Hz), 7.61 (1 H, dd, J=8.4, 4.3 Hz), 7.47 (1 H, dd, J=8.4, 1.6 Hz), 2.69 (3 H, s).
References: [1] Patent: WO2009/126584, 2009, A1, . Location in patent: Page/Page column 62-63.
  • 5
  • [ 63668-59-7 ]
  • [ 917-54-4 ]
  • [ 13210-29-2 ]
References: [1] Patent: US2011/166124, 2011, A1, . Location in patent: Page/Page column 49.
  • 6
  • [ 874-24-8 ]
  • [ 75-16-1 ]
  • [ 13210-29-2 ]
References: [1] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 13, p. 3398 - 3404.
  • 7
  • [ 75-77-4 ]
  • [ 174668-95-2 ]
  • [ 13210-29-2 ]
References: [1] Angewandte Chemie - International Edition, 2014, vol. 53, # 34, p. 9026 - 9029[2] Angew. Chem., 2014, vol. 126, # 34, p. 9172 - 9175,4.
  • 8
  • [ 81376-88-7 ]
  • [ 13210-29-2 ]
References: [1] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 3, p. 665 - 668.
  • 9
  • [ 874-24-8 ]
  • [ 13210-29-2 ]
References: [1] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 3, p. 665 - 668.
  • 10
  • [ 73406-50-5 ]
  • [ 13210-29-2 ]
References: [1] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 3, p. 665 - 668.
  • 11
  • [ 7606-13-5 ]
  • [ 13210-29-2 ]
References: [1] Angewandte Chemie - International Edition, 2014, vol. 53, # 34, p. 9026 - 9029[2] Angew. Chem., 2014, vol. 126, # 34, p. 9172 - 9175,4.
  • 12
  • [ 107096-06-0 ]
  • [ 13210-29-2 ]
References: [1] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 3, p. 665 - 668.
  • 13
  • [ 107096-06-0 ]
  • [ 141-78-6 ]
  • [ 13210-29-2 ]
  • [ 81376-88-7 ]
References: [1] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 3, p. 665 - 668.
[2] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 3, p. 665 - 668.
 

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