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Chemical Structure| 22620-27-5 Chemical Structure| 22620-27-5

Structure of 22620-27-5

Chemical Structure| 22620-27-5

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Product Details of [ 22620-27-5 ]

CAS No. :22620-27-5
Formula : C6H4ClNO2
M.W : 157.55
SMILES Code : C1=C(C=NC=C1Cl)C(O)=O
MDL No. :MFCD00128901
InChI Key :XYLPLVUYPAPCML-UHFFFAOYSA-N
Pubchem ID :247986

Safety of [ 22620-27-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 22620-27-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 36.21
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.

1.07
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

1.01
Log Po/w (WLOGP)?

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

1.43
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.

-0.51
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

1.39
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.

-1.83
Solubility 2.32 mg/ml ; 0.0148 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.

-1.65
Solubility 3.5 mg/ml ; 0.0222 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

-2.0
Solubility 1.57 mg/ml ; 0.00998 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.

-6.54 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.

0.56

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)

1.3

Application In Synthesis of [ 22620-27-5 ]

* 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 [ 22620-27-5 ]
  • Downstream synthetic route of [ 22620-27-5 ]

[ 22620-27-5 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 22620-27-5 ]
  • [ 79-22-1 ]
  • [ 22620-34-4 ]
YieldReaction ConditionsOperation in experiment
76%
Stage #1: With triethylamine In tetrahydrofuran at 0 - 20℃;
Stage #2: With lithium aluminium tetrahydride In tetrahydrofuran for 0.5 h;
A.
(5-Chloro-pyridin-3-yl)-methanol
To a solution of 5-chloro-nicotinic acid (2 g, 12.7 mmol) and TEA (1.52 g, 15 mmol) in THF (30 mL) was added slowly methyl chloroformate (1.42 g, 15 mmol) at 0° C.
The resulting mixture was stirred at room temperature overnight.
The reaction was diluted with ethyl acetate, washed with saturated ammonia chloride and dried over anhydrous sodium sulfate.
The organic layer was concentrated to give the crude product (2.8 g, crude), which was dissolved in THF (40 mL) and cooled to -78° C. Lithium aluminium hydride (570 mg, 15 mmol) was added portion-wise.
The resulting mixture was stirred for 30 min.
The reaction was quenched with aqueous sodium hydroxide and extracted with ethyl acetate.
The combined organic layers were dried over anhydrous sodium sulfate and concentrated to give the crude product, which was purified by silica gel column chromatography (30percent ethyl acetate in petroleum ether) to afford the title compound (1.4 g, 9.72 mmol, 76percent yield). MS (ESI) m/z 144.1 [M+H]+.
References: [1] Patent: US2015/175557, 2015, A1, . Location in patent: Paragraph 0321.
  • 2
  • [ 22620-27-5 ]
  • [ 22620-34-4 ]
YieldReaction ConditionsOperation in experiment
31% With diborane In tetrahydrofuran at 0 - 20℃; for 72 h; Inert atmosphere 1.3.2 (5-Chloropyridin-3-yl)methanol (AOH-2)
5-Chloronicotinic acid (1 g, 6.35 mmol) was dissolved in dry THF (20 mL) in a N2flushed flask and 1 M BH3in THF (25.4 mL, 25.4 mmol) was added via a syringe at 0°C. The mixture was stirred at RT for 72 h. The reaction mixture was cooled in an ice bath and aqueous saturated K2C03(50 mL) was added cautiously. The organic solvent was removed in vacuo and the residue was extracted withEtOAc (2x 50 mL). The combined organic layers were washed with saturated aqueous NaHC03(2x 25 mL) and brine (2x 25 mL) before drying on Na2S04and concentration in vacuo to give a colorless oil. The product was purified using column chromatography (silica, heptane/EtOAc, 1 :1 ) to give the desired product (285 mg, 31 percent) as a yellow oil which partially solidified upon standing.
References: [1] Patent: WO2015/90599, 2015, A1, . Location in patent: Page/Page column 53.
[2] Patent: US2014/107340, 2014, A1, .
 

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Technical Information

Categories

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