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Chemical Structure| 39891-09-3 Chemical Structure| 39891-09-3

Structure of 39891-09-3

Chemical Structure| 39891-09-3

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Product Details of [ 39891-09-3 ]

CAS No. :39891-09-3
Formula : C7H5ClN2
M.W : 152.58
SMILES Code : N#CCC1=CN=C(Cl)C=C1
MDL No. :MFCD04112495
InChI Key :BLGUCBUETMYJTB-UHFFFAOYSA-N
Pubchem ID :1475128

Safety of [ 39891-09-3 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H315-H318-H335
Precautionary Statements:P261-P280-P301+P310-P305+P351+P338
Class:8(6.1)
UN#:2923
Packing Group:

Computational Chemistry of [ 39891-09-3 ] 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 2.0
Num. H-bond donors 0.0
Molar Refractivity 38.77
TPSA ?

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

36.68 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.4
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

1.47
Log Po/w (WLOGP)?

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

1.8
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.

0.73
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

2.27
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.53

Water Solubility

Log S (ESOL):?

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

-2.09
Solubility 1.24 mg/ml ; 0.00813 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.85
Solubility 2.17 mg/ml ; 0.0142 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

-3.12
Solubility 0.117 mg/ml ; 0.000767 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

Yes
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.

-6.19 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

1.0 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)

1.69

Application In Synthesis of [ 39891-09-3 ]

* 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 [ 39891-09-3 ]

[ 39891-09-3 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 39891-09-3 ]
  • [ 197376-47-9 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; In ethanol; water; (6-Chloro-pyridin-3-yl)-acetic acid ethyl ester To a solution of EtOH (27 mL), concentrated H2SO4 (10 mL) was added dropwise and 2-chloropyridine-5-acetonitrile (2.00 g, 13.1 mmol) was added portionwise. The solution was stirred at 100C for three hours. The mixture was added dropwise to a solution of NaHCO3 (30.00 g) in H2O (100 mL) and it was extracted twice with DCM. The organic layer were collected, dried and evaporated to give the title compound (2.60 g, quant.) C9H10ClNO2 Mass (calculated) [199]; (found) [M+H]+ = 200.
  • 2
  • [ 39891-09-3 ]
  • [ 64-17-5 ]
  • [ 197376-47-9 ]
YieldReaction ConditionsOperation in experiment
100% With sulfuric acid; at 100℃; for 3h; To a solution of EtOH (27 mL), concentrated H2SO4 (10 mL) was added dropwise and 2-chloropyridine-5-acetonitrile (2.00 g, 13.1 mmol) was added portionwise. The solution was stirred at 100 C. for three hours. The mixture was added dropwise to a solution of NaHCO3 (30.00 g) in H2O (100 mL) and it was extracted twice with DCM. The organic layer were collected, dried and evaporated to give the title compound (2.60 g, quant.) (0395) C9H10ClNO2 Mass (calculated) [199]; (found) [M+H]+=200.
75% Step 2. Synthesis of (6-chloropyridin-3-yl) acetic acid ethyl ester. 10 g (65 5 mmol) (6-chloropyriotadiotan-3-yl)acetoniotatriotale were added to a mixture of 122 mL ethanol and 46 mL cone sulfuric acid and the mixture stirred under reflux for 5 h After cooling to ambient temperature, the reaction mixture was slowly added dropwise. while stirring, to a mixture of 161 g sodium bicarbonate and 450 mL water The aqueous phase was extracted with DCM (three times with 300 mL each time) The combined organic phases were dried over sodium sulfate, filtered and concentrated on a rotary evaporator The crude oil was purified by silica gei chromatography, eluted using a gradient of 2/98(v/v) EtOAc/hexanes to 9/91 (v/v) EtOAc/hexanes to afford 9 8 g (75%) of product as clear oil ESI-MS m/z 200 (MH)f
To a solution at-5 C of 44 mL of absolute ethanol in 155 mL of chloroform under nitrogen was added dropwise 45 mL of acetyl chloride. After 0.5 hours a solution of 8.46 g (55.4 MMOL) of Preparatory Compound E in 71 mL of chloroform was added dropwise keeping the temperature at 0 C or below. The mixture was then kept at 0 C for 4 hours and was then allowed to warm to room temperature overnight (about 22 C). Ethyl ether was added (350 mL) with cooling and the mixture was stirred for several minutes and was then filtered through a medium porosity sintered glass funnel always careful to keep a layer of ether over the white solid. After washing with an ample amount of ether, the solid/ether mixture was washed into a 1 L three-neck round-bottomed flask fitted with a mechanical stirrer and was then diluted with 400 mL of ether and was treated dropwise with 12.34 g (122 mmol, 2.2 equiv. ) of triethylamine in ether while cooling. The contents were stirred overnight under nitrogen. The mixture was filtered, the filtrate was dried over sodium sulfate and was concentrated to give 9.91 g (90%) of Preparatory Compound K, ethyl 2- (6-CHLORO-3-PYRIDINYL) ethanimidoate, as an oil.
22.0 g (144 mmol) of (6-chloropyridin-3-yl)acetonitrile are added to a mixture of 270 ml of ethanol and 101 ml conc. sulfuric acid, and the mixture is stirred under reflux for 24 h. With stirring, the reaction mixture is then slowly added dropwise to a mixture of 350 g of sodium bicarbonate and 1 liter of water. The aqueous phase is extracted with dichloromethane (five times 400 ml each). The combined organic phases are dried over sodium sulfate, filtered and freed from the solvent using a rotary evaporator. This gives 23.1 g (80% of theory) of the title compound, which is reacted without further purification.1H-NMR (400 MHz, DMSO-d6): delta=8.32 (d, 1H), 7.78 (dd, 1H), 7.49 (d, 1H), 4.10 (q, 2H), 3.77 (s, 2H), 1.19 (t, 3H).LC-MS (Method 3): Rt=1.91 min; MS (ESIpos): m/z=200 [M+H]+.
13 g With sulfuric acid; for 4h;Reflux; 15.2 g 2-chloropyridin-5-ylacetonitrile was added to a 250 ml four-mouthed flask. Add 150 ml ethanol. 10ml 98% concentrated sulfuric acid. Heat to reflux. Reflux reaction for 4 hours, reaction finishes, prolapsed ethanol, add 100 g water to stir, is neutral pH the sodium carbonate is used to regulate, filter, to obtain 2-chloro pyridine ethyl acetate 13 g.

  • 3
  • [ 21543-49-7 ]
  • [ 143-33-9 ]
  • [ 39891-09-3 ]
YieldReaction ConditionsOperation in experiment
Step 2: Preparation of (6-chloropyridin-3-yl) acetonitrile; To a-78 C solution of (6-chloropyridin-3-yl) methanol from Step 1 (7.5 g) and triethylamine (8.7 mL) in dichloromethane (250 mL) was slowly added methanesulphonyl chloride (4.5 mL). The reaction mixture was stirred at 0 C for 1 hour. Then poured into ice and HC1 (1N), adjusted pH at 4 with saturated aqueous disodium hydrogen phosphate and partitioned. The aqueous layer was extracted with dichloromethane (1 X 150 mL). The combined extracts were washed with brine, dried with magnesium sulfate and the solvent removed in vacuo. The residue was dissolved in DMF (100 mL) and sodium cyanide (2.8 g) was added. The reaction mixture was stirred at room temperature for 3 hours and poured into ice and water (100 mL). Extracted with ethyl acetate (2 X 100 mL). The combined extracts were washed with brine, dried with magnesium sulfate and the solvent removed in vacuo. The residue was purified by chromatography on Si02 using ethyl acetate and hexanes (1: 5 to 1: 2) to yield the title compound. 'H NMR (CD3COCD3) 8 8.45 (1H, s), 7.90 (1H, d), 7.50 (1H, d), 4.06 (2H, s).
 

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Technical Information

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