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Chemical Structure| 623-47-2 Chemical Structure| 623-47-2

Structure of 623-47-2

Chemical Structure| 623-47-2

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Product Details of [ 623-47-2 ]

CAS No. :623-47-2
Formula : C5H6O2
M.W : 98.10
SMILES Code : C#CC(OCC)=O
MDL No. :MFCD00009184
InChI Key :FMVJYQGSRWVMQV-UHFFFAOYSA-N
Pubchem ID :12182

Safety of [ 623-47-2 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H315-H319-H335
Precautionary Statements:P501-P240-P210-P233-P243-P241-P242-P264-P280-P370+P378-P337+P313-P305+P351+P338-P362+P364-P303+P361+P353-P332+P313-P403+P235
Class:3
UN#:3272
Packing Group:

Computational Chemistry of [ 623-47-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 0
Fraction Csp3 0.4
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 25.6
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.84
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

0.96
Log Po/w (WLOGP)?

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

0.26
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.

0.79
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

0.5
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.87

Water Solubility

Log S (ESOL):?

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

-0.92
Solubility 11.8 mg/ml ; 0.12 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.

-1.1
Solubility 7.8 mg/ml ; 0.0795 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

-0.36
Solubility 42.7 mg/ml ; 0.436 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.

-6.22 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

2.0 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)

2.13

Application In Synthesis of [ 623-47-2 ]

* 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 [ 623-47-2 ]
  • Downstream synthetic route of [ 623-47-2 ]

[ 623-47-2 ] Synthesis Path-Upstream   1~7

  • 1
  • [ 108-89-4 ]
  • [ 623-47-2 ]
  • [ 51135-70-7 ]
YieldReaction ConditionsOperation in experiment
59.8%
Stage #1: With N-hydroxy-2,4-dinitrobenzenamine In acetonitrile at 20℃; for 12 h;
Stage #2: With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 10 h;
2,4-Dinitrophenylhydroxylamine (13.00 g, 65.3 mmol) was added to a 500 mL vial, dissolved in 200 mL of acetonitrile, and 4-methylpyridine (9.12 g, 97.9 mmol) was added at room temperature for 12 h at room temperature. The solution was spun dry, 200 mL of DMF and potassium carbonate (27.07 g, 195.9 mmol) were added, ethyl propiolate (9.60 g, 97.9 mmol) was added in one portion, and reacted at room temperature for 10 h. The reaction was completed by TLC, and 300 mL of water and EA, liquid separation, water layer was extracted with 300 mL of EA, and the organic phase was combined, washed with 300 mL of brine, dried over anhydrous sodium sulfate, filtered and evaporatedElution with PE/EA=20/1-10/1 gave 7.97 g of pale yellow solid, yield 59.8percent.
53%
Stage #1: With mesitylenesulfonylhydroxylamine In dichloromethane at 0℃; for 2 h;
Stage #2: With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18 h;
General procedure: These were made using MSH or DNPH as detailed below, unless otherwise stated. A fresh solution of MSH23 in CH2Cl2 (1 equiv) was added to the substituted pyridine (1 equiv) in CH2Cl2 (10 mL) at 0 °C. After 2 h, the solvent was removed in vacuo. Alternatively, a solution of DNPH12 (1 equiv) and the substituted pyridine (1 equiv) in MeCN (40 mL) was heated at 40 °C for 18 h. The solvent was removed in vacuo. The method continues by taking the residue from either method in dry DMF (8 mL), and then ethyl propiolate (1 equiv) and K2CO3 (2 equiv) were added, and the suspension stirred at room temperature for 18 h. The reaction mixture was diluted with water and extracted twice with EtOAc. The combined organic phases were washed three times with water then with brine, dried (Na2SO4) and the solvent removed in vacuo. Chromatography (eluting with a hexanes: EtOAc gradient, unless otherwise stated) gave the pyrazolo[1,5-a]pyridine.
53%
Stage #1: With mesitylenesulfonylhydroxylamine In dichloromethane at 0℃; for 2 h;
Stage #2: With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18 h;
Step 2.1 : A fresh solution of O-(mesitylsulfonyl)hydroxylamine in CH2CI2 (6.0 ml_, 0.44 mol L"1, 2.6 mmol) [T. Eichenberger et al., HeIv. Chim. Acta 1986, 69(6), 1521] was added to 4-methylpyridine (1: X = Me) (248 mg, 2.66 mmol) in CH2CI2 (10 mL) at 0 0C. After 2 h, the solvent was removed in vacuo. The residue was taken up in dry DMF (8 mL), then ethyl propiolate (0.25 mL, 2.5 mmol) and K2CO3 (450 mg, 3.26 mmol) were added, and the suspension stirred at room temperature for 18 h. The reaction mixture was diluted with water and extracted twice with EtOAc. The combined organic phases were washed three times with water then with brine, dried (Na2SO4) and the solvent removed in vacuo. Chromatography (eluting with hexanes: EtOAc 97:3 to 95:5 to 9:1) gave ethyl 5-methyl- pyrazolo[1 ,5-a]pyridine-3-carboxyIate (4: X = Me) as a pale brown solid (175 mg, 53percent). 1H NMR δ (400 MHz, CDCI3) 8.39 (d, J 7.1 Hz, 1 H)1 8.34 (s, 1H), 7.93 (s, 1H), 6.76 (dd, J 7.1 , 1.9 Hz, 1 H), 4.38 (q, J 7.1 Hz, 2H), 2.47 (s, 3H), 1.41 (t, J 7.1 Hz, 3H). LCMS (APCI+) 205 (MH+, 100percent).
References: [1] Patent: CN108948019, 2018, A, . Location in patent: Paragraph 0548; 0550; 0551.
[2] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 1, p. 69 - 85.
[3] Patent: WO2009/8748, 2009, A1, . Location in patent: Page/Page column 56.
  • 2
  • [ 51135-56-9 ]
  • [ 623-47-2 ]
  • [ 51135-70-7 ]
References: [1] Patent: WO2015/86693, 2015, A1, . Location in patent: Page/Page column 52.
  • 3
  • [ 623-47-2 ]
  • [ 85386-14-7 ]
References: [1] Journal of Organic Chemistry, 1996, vol. 61, # 7, p. 2470 - 2483.
  • 4
  • [ 944709-38-0 ]
  • [ 623-47-2 ]
  • [ 105174-97-8 ]
  • [ 111303-36-7 ]
References: [1] Patent: WO2005/26149, 2005, A1, . Location in patent: Page/Page column 105.
  • 5
  • [ 74213-24-4 ]
  • [ 623-47-2 ]
  • [ 105174-97-8 ]
  • [ 111303-36-7 ]
References: [1] Journal of Heterocyclic Chemistry, 1987, vol. 24, # 1, p. 43 - 46.
[2] Organic Process Research and Development, 2011, vol. 15, # 5, p. 1073 - 1080.
  • 6
  • [ 50-00-0 ]
  • [ 106-40-1 ]
  • [ 623-47-2 ]
  • [ 481054-89-1 ]
References: [1] ACS Catalysis, 2017, vol. 7, # 3, p. 2007 - 2021.
  • 7
  • [ 623-47-2 ]
  • [ 1355249-29-4 ]
References: [1] Patent: WO2012/6760, 2012, A1, .
[2] Patent: WO2012/8999, 2012, A2, .
 

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