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Chemical Structure| 1201924-31-3 Chemical Structure| 1201924-31-3

Structure of 1201924-31-3

Chemical Structure| 1201924-31-3

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Product Details of [ 1201924-31-3 ]

CAS No. :1201924-31-3
Formula : C7H5ClN2
M.W : 152.58
SMILES Code : N#CC1=NC(Cl)=CC=C1C
MDL No. :MFCD16658734
InChI Key :GRLXSZKHRDKVTE-UHFFFAOYSA-N
Pubchem ID :46856278

Safety of [ 1201924-31-3 ]

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

Computational Chemistry of [ 1201924-31-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 38.93
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.

1.76
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

2.23
Log Po/w (WLOGP)?

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

1.92
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

2.4
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.81

Water Solubility

Log S (ESOL):?

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

-2.63
Solubility 0.354 mg/ml ; 0.00232 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.

-2.64
Solubility 0.353 mg/ml ; 0.00231 mol/l
Class?

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

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

-3.1
Solubility 0.122 mg/ml ; 0.0008 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.

-5.65 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)

1.92

Application In Synthesis of [ 1201924-31-3 ]

* 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 [ 1201924-31-3 ]

[ 1201924-31-3 ] Synthesis Path-Downstream   1~19

  • 1
  • [ 20970-75-6 ]
  • [ 1201924-31-3 ]
  • 2
  • [ 159727-88-5 ]
  • [ 1201924-31-3 ]
YieldReaction ConditionsOperation in experiment
Step 2. 6-Chloro-3-methylpyridine-2-carbonitrile3-Methylpyridme-2-carbordtrile 1 -oxide (8.42 g, 62.8 mmol) was stirred in refluxing POCl3 (60 mL, 646 mmol) for 6 hours. The mixture was cooled to room temperature and slowly poured into ice- water. The resulting beige precipitate was collected by filtration to give the title compound.1H NMR (600 MHz, CDCl3): delta 7.62 (d, J- 8.4 Hz, 1 H), 7.43 (d, J- 8.4 Hz, 1 H), 2.53 (s, 3 H).
With trichlorophosphate; In toluene; at 90.0℃; for 1.5h; To a round bottom flask is added 3-methyl-l-oxo-pyridine-2- carbonitrile (16.2 g, 120.77 mmoles), toluene (8 mL), and phosphoryl chloride (16.83 mL; 181.2 mmoles). The mixture is stirred at 90 C for 90 minutes, cooled to RT, and added dropwise to aqueous 2M KH2PO4 (483 mL; 966 mmoles). The mixture is stirred 30 minutes, and the layers are separated. The organic layer is dried over MgS04, filtered, and concentrated to 6-chloro-3-methyl-pyridine-2-carbonitril: Mass spectrum (m/z): 153.0 (M+H)+. Phenylboronic acid (17.94 g, 144.9 mmoles), toluene (130 mL), sodium carbonate (190.2 g, 362.31 mmoles), bis(triphenylphosphine)palladium(II) chloride (856 mg; 1.21 mmoles) are added to this crude material. The mixture is stirred at 80C for 1 hour and cooled to RT. The layers are separated, and the organic layer is dried over MgS04, filtered, and concentrated. The material was purified by silica gel chromatography (400 g ISCO cartridge) using methylene chloride in hexanes from 20 to 100% to afford 3-methyl-6-phenyl-pyridine-2-carbonitrile (6.7 g, 28.6%). Mass spectrum (m/z): 195.1 (M+H)+.
With trichlorophosphate; for 1h;Reflux; A mixture of the product from Step 1 (1.2 g, 8.95 mmol) in POCl3 (29.7 g, 194 mmol) was stirred at reflux for 1 h. The mixture was cooled to RT, poured into 50 mL of water, and basified with saturated, aqueous NaHCC to pH 7-8, and extracted with EtOAc (100 mL). The organic phase was washed with brine (50 mL), dried over Na2SC>4, filtered, and concentrated in vacuo to give the title compound as a solid, which was used in the next step without further purification. LRMS m/z (M+H) 153.1 found, 153.0 required.
  • 3
  • [ 1201924-31-3 ]
  • [ 878207-92-2 ]
  • 4
  • [ 1201924-31-3 ]
  • [ 1201924-32-4 ]
YieldReaction ConditionsOperation in experiment
Step 3. 6-Chloro-3 -methylpyridine-2-carboxylic acid6-Chloro-3-methylrhoyridine-2-carbonitrile (2.95 g, 19.3 mmol) and Potassium hydroxide (3.25 g, 58 mmol) were stirred in refluxing water (60 mL) for 2 hours. The mixture was cooled to room temperature, 30 mL of 2 N HCl was added, followed by the addition of water. The resulting mixture was extracted with EtOAc (3x). The combined organic extracts were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo to give the title compound as a white solid.1H NMR (600 MHz, DMSO): delta 13.45 (br s, 1 H), 7.81 (d, J= 8.4 Hz5 1 H), 7.55 (d, J- 8.4 Hz, 1 H), 2.39 (s, 3 H).
  • 5
  • [ 1201924-31-3 ]
  • [ 1201924-34-6 ]
  • 6
  • [ 1201924-31-3 ]
  • [ 98-80-6 ]
  • 3-methyl-6-phenyl-pyridine-2-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
6.7 g With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In toluene; at 80.0℃; for 1h; To a round bottom flask is added 3-methyl-l-oxo-pyridine-2- carbonitrile (16.2 g, 120.77 mmoles), toluene (8 mL), and phosphoryl chloride (16.83 mL; 181.2 mmoles). The mixture is stirred at 90 C for 90 minutes, cooled to RT, and added dropwise to aqueous 2M KH2PO4 (483 mL; 966 mmoles). The mixture is stirred 30 minutes, and the layers are separated. The organic layer is dried over MgS04, filtered, and concentrated to 6-chloro-3-methyl-pyridine-2-carbonitril: Mass spectrum (m/z): 153.0 (M+H)+. Phenylboronic acid (17.94 g, 144.9 mmoles), toluene (130 mL), sodium carbonate (190.2 g, 362.31 mmoles), bis(triphenylphosphine)palladium(II) chloride (856 mg; 1.21 mmoles) are added to this crude material. The mixture is stirred at 80C for 1 hour and cooled to RT. The layers are separated, and the organic layer is dried over MgS04, filtered, and concentrated. The material was purified by silica gel chromatography (400 g ISCO cartridge) using methylene chloride in hexanes from 20 to 100% to afford 3-methyl-6-phenyl-pyridine-2-carbonitrile (6.7 g, 28.6%). Mass spectrum (m/z): 195.1 (M+H)+.
  • 7
  • [ 1201924-31-3 ]
  • 3-methyl-6-phenyl-pyridine-2-carboxylic acid [ No CAS ]
  • 8
  • [ 1201924-31-3 ]
  • methyl 2,4-dimethyl-3-[(3-methyl-6-phenyl-pyridine-2-carbonyl)amino]benzoate [ No CAS ]
  • 9
  • [ 1201924-31-3 ]
  • 2,4-dimethyl-3-[(3-methyl-6-phenyl-pyridine-2-carbonyl)amino]benzoic aicd [ No CAS ]
  • 10
  • [ 1201924-31-3 ]
  • 3-methyl-6-phenyl-pyridine-2-carbonyl chloride [ No CAS ]
  • 11
  • [ 1201924-31-3 ]
  • N-ethyl-N-(2-(6-(2-hydroxypropan-2-yl)-5-methylpyridin-2-yl)ethyl)-2-(2H-1,2,3-triazol-2-yl)benzamide [ No CAS ]
  • 12
  • [ 1201924-31-3 ]
  • 6-(2-(ethylamino)ethyl)-3-methylpicolinonitrile [ No CAS ]
  • 13
  • [ 1201924-31-3 ]
  • N-(2-(6-cyano-5-methylpyridin-2-yl)ethyl)-N-ethyl-2-(2H-1,2,3-triazol-2-yl)benzamide [ No CAS ]
  • 14
  • [ 1201924-31-3 ]
  • N-(2-(6-acetyl-5-methylpyridin-2-yl)ethyl)-N-ethyl-2-(2H-1,2,3-triazol-2-yl)benzamide [ No CAS ]
  • 15
  • [ 1201924-31-3 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • 3-methyl-6-vinylpicolinonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 90.0℃;Inert atmosphere; To a stirred mixture of the product from Step 2 (200 mg, 1.31 mmol), Pd(Ph3P)4 (76 mg, 0.066 mmol), and Na2C03 (278 mg, 2.62 mmol) in toluene (4 mL), EtOH (2 mL), and water (1 mL) was added potassium vinyltrifluoroborate (263 mg, 1.97 mmol) under N2. The resulting mixture was stirred at 90C overnight. The mixture was cooled to RT, and then the organic layer was separated. The organic phase was washed with water (5 mL x 2), dried over Na2SC>4, filtered, and concentrated in vacuo. The residue was purified by prep-TLC (50% EtOAc in petroleum ether) to give the title compound as a oil. LRMS m/z (M+H) 145.1 found, 145.1 required.
  • 16
  • [ 1201924-31-3 ]
  • [ 84477-72-5 ]
  • 6-(3,3-dimethylpiperazin-1-yl)-3-methylpyridine-2-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With caesium carbonate; In 1-methyl-pyrrolidin-2-one; at 100.0℃; A mixture of <strong>[1201924-31-3]6-chloro-3-methyl-pyridine-2-carbonitrile</strong> (914 mg, 5.99 mmol), 2,2- dimethylpiperazine (1000 ilL, 7.30 mmol) and cesium carbonate (2.27 g, 6.97 mmol) in NMP (12 mL) is heated at 100C overnight. The reaction is cooled down to room temperature and water (120 mL) is added. The mixture is extracted with Et20 (3 x 50 mL). The combined organic phases are washed with water (60 mL) and brine (60 mL), dried over Na2SO4 and concentrated under reduced pressure. The crude material isused without further purification in the next step (1.082g, 69%). ESI-MS m/z calc. 230.15315, found 230.68 (M+1)+; Retention time: 1.03 minutes using Method L.
  • 17
  • [ 1201924-31-3 ]
  • [ 84477-72-5 ]
  • methyl 6-(3,3-dimethylpiperazin-1-yl)-3-methylpyridine-2-carboxylate hydrochloride [ No CAS ]
  • 18
  • [ 1201924-31-3 ]
  • [ 75-03-6 ]
  • 6-chloro-5-ethyl-3-methylpicolinonitrile [ No CAS ]
  • 6-chloro-4-ethyl-3-methylpicolinonitrile [ No CAS ]
  • 19
  • [ 75-30-9 ]
  • [ 1201924-31-3 ]
  • 6-chloro-5-isopropyl-3-methylpyridine-2-carbonitrile [ No CAS ]
 

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Technical Information

Categories

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