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Chemical Structure| 19235-89-3 Chemical Structure| 19235-89-3

Structure of 19235-89-3

Chemical Structure| 19235-89-3

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Product Details of [ 19235-89-3 ]

CAS No. :19235-89-3
Formula : C6H3ClN2
M.W : 138.55
SMILES Code : C1=C(Cl)C=CN=C1C#N
MDL No. :MFCD06009833
InChI Key :DYEZRXLVZMZHQT-UHFFFAOYSA-N
Pubchem ID :693342

Safety of [ 19235-89-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 19235-89-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 33.96
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.

1.45
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

1.53
Log Po/w (WLOGP)?

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

1.61
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.

0.4
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

1.98
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.39

Water Solubility

Log S (ESOL):?

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

-2.16
Solubility 0.967 mg/ml ; 0.00698 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.

-1.91
Solubility 1.71 mg/ml ; 0.0123 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

-2.7
Solubility 0.278 mg/ml ; 0.002 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.

-6.06 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)

1.56

Application In Synthesis of [ 19235-89-3 ]

* 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 [ 19235-89-3 ]

[ 19235-89-3 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 19235-89-3 ]
  • [ 917-64-6 ]
  • [ 60159-37-7 ]
YieldReaction ConditionsOperation in experiment
76% Step A Nitrile I (60 g, 0.42 mol) is dissolved in THF (1000 ml) in a 2 l three-necked flask fitted with stirrer and thermometer under an N2 protective-gas atmosphere and cooled to 0 C. by means of an ice bath. Commercially available MeMgl (200 ml of a 3 M solution in THF, 0.6 mmol) is slowly added over the course of about 45 min. A clear, dark solution initially forms. The dropwise addition rate of the MeMgl addition is adjusted so that the solution temperature in the reaction vessel is between 0-10 C. When all the Grignard reagent has been added, a green suspension is obtained, which is stirred at 0 C. for a further 2 h. The reaction mixture is then added to ice-water (1500 ml). 2 M HCl is added until the reaction mixture has an approx. pH2. The mixture is stirred for a further 15 min. and then extracted a number of times (addition of EtOAc and water). The combined organic phases are washed with aqueous saturated sodium chloride solution and dried using Na2SO4. All the solvents are removed by distillation under reduced pressure in a rotary evaporator, giving 66 g of yellow-brown oil as crude product. The crude product is purified by means of column chromatography (800 g of Si60, MTBE). The suitable fractions (characterised by TLC analysis) are combined. Removal of the solvents gives ketone II (51 g, 0.32 mol, 76% yield) as clear dark oil. LC-MS: tR=1.829 min (UV=220 nm), tR=1.842 min. (TIC, with [M+H]+=156); 1H NMR (300 MHz, CDCl3) δ 8.58 (d, 1H), 8.03 (dd, J=2.1, 0.4, 1H), 7.47 (dd, J=5.2, 2.1, 1H), 2.71 (d, J=3.2, 3H).
  • 3
  • [ 19235-89-3 ]
  • [ 60159-37-7 ]
YieldReaction ConditionsOperation in experiment
3.60 g (60%) With hydrogenchloride; MeMgI; In benzene; 2-Acetyl-4-chloropyridine: To a solution of 4-chloro-2-pyridinecarbonitrile (5.35 g, 38.6 mmol) in benzene (50 ml) and ether (50 ml) cooled to 0 C. was added dropwise over 20 min a 2M solution of MeMgI in ether (23 ml, 46.3 mmol). After 0.5 h, the mixture was allowed to warm to ambient temperature, and stirring continued for 2 h. The mixture was cooled to 0 C. and 2M aqueous HCl (100 ml) added. The mixture was made basic with saturated aqueous sodium bicarbonate (~80 ml) and the organic layer separated and dried (MgSO4). After removal of solvent, the residue was purified by flash chromatography eluding with ethyl acetate/hexane (1:5) to afford 3.60 g (60%) of 2-acetyl-4-chloropyridine. 1H-NMR (DMSO-d6) δ: 8.59 (1H, d, J=5.1 Hz), 8.04 (1H, d, J=1.8 Hz), 7.47 (1H, dd, J=1.8, 5.1 Hz), 2.72 (3H, s).
3.60 g (60%) With hydrogenchloride; MeMgI; In benzene; 2-Acetyl-4-chloropyridine: To a solution of 4-chloro-2-pyridinecarbonitrile (5.35 g, 38.6 mmol) in benzene (50 ml) and ether (50 ml) cooled to 0 C was added dropwise over 20 min a 2M solution of MeMgI in ether (23 ml, 46.3 mmol). After 0.5 h, the mixture was allowed to warm to ambient temperature, and stirring continued for 2 hours. The mixture was cooled to 0 C and 2M aqueous HCl (100 ml) added. Themixture was made basic with saturated aqueous sodium bicarbonate (~80 ml) and the organic layer separated and dried (MgSO4). After removal of solvent, the residue was purified by flash chromatography eluding with ethyl acetate/hexane (1:5) to afford 3.60 g (60%) of 2-acetyl-4-chloropyridine. 1H-NMR (DMSO-d6) 8.59 (1 H, d, J=5.1 Hz), 8.04 (1 H, d, J=1.8 Hz), 7.47 (1 H, dd, J=1.8, 5.1 Hz), 2.72 (3 H, s).
  • 4
  • [ 19235-89-3 ]
  • [ 98139-15-2 ]
  • 5
  • [ 19235-89-3 ]
  • [ 75-16-1 ]
  • [ 60159-37-7 ]
YieldReaction ConditionsOperation in experiment
660 mg In tetrahydrofuran; at 0℃; for 2h; To a mixture of A-4 (3 g, 21.65 mmol) in TI-IF (60 mL) was added bromo(methyl)magnesium (14.44 mL, 43.31 mmol) at 0C, then the mixture was stirred at 0C for 2 hours. The reaction mixture was added to ice-water (50 mL) and 2 M HCI (25 mL), stirred for 15 minutes, and extracted with EtOAc (50 mL x 2). The combined organic phase was washed with water (30 mL) and brine (30 mL), dried over Na2SO4, filtered and concentrated to give the crude product, which was purified by flash chromatography on silica gel (EtOAc in PE = 0% to 10% to 20%) to afford A-5 (660 mg, 3.31 mmol) as a solid. ‘HNMR (400MHz, CDCI3) oH = 8.59 (d, 1H), 8.04 (d, 1H), 7.48 (dd, 1H), 2.73 (s, 3H). LCMS Rt = 0.640 mm using Method B, MS ESI calcd. for C7H7CINO {M+Hj 156.0, found 155.8.
 

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