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Structure of 1021871-35-1

Chemical Structure| 1021871-35-1

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Product Details of [ 1021871-35-1 ]

CAS No. :1021871-35-1
Formula : C8H6ClNO
M.W : 167.59
SMILES Code : N#CC1=CC(CO)=CC(Cl)=C1
MDL No. :MFCD18392447
InChI Key :XNOWXYQLTYKTNC-UHFFFAOYSA-N
Pubchem ID :58369542

Safety of [ 1021871-35-1 ]

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

Computational Chemistry of [ 1021871-35-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 42.29
TPSA ?

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

44.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.77
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

1.99
Log Po/w (WLOGP)?

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

1.55
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.

1.44
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

2.28
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.

-2.47
Solubility 0.567 mg/ml ; 0.00339 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.

-2.54
Solubility 0.483 mg/ml ; 0.00288 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

-2.92
Solubility 0.201 mg/ml ; 0.0012 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.

-5.91 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)

1.66

Application In Synthesis of [ 1021871-35-1 ]

* 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 [ 1021871-35-1 ]

[ 1021871-35-1 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 327056-72-4 ]
  • [ 1021871-35-1 ]
YieldReaction ConditionsOperation in experiment
(Step 2) To a mixed solution of 3-chloro-5-cyanobenzoate (1.13 g) obtained in Step 1 in tetrahydrofuran:ethanol=10:1 (33 ml) was added lithium tetrahydroborate (0.19 g) at 0°C. After stirring at 60°C for 2 hr, the reaction solution was quenched with ice and extracted with ethyl acetate. The extract was washed with 1N hydrochloric acid and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was treated by silica gel chromatography (ethyl acetate:hexane=1:1) to give 3-chloro-5-(hydroxymethyl)benzonitrile (0.60 g) as a white solid. 1H-NMR (CDCl3) delta ppm 1.97 (1 H, t, J=5.65 Hz) 4.75 (2 H, d, J=5.84 Hz) 7.56 (2 H, s) 7.61 (1 H, s).
  • 2
  • [ 1021871-35-1 ]
  • [ 1021871-36-2 ]
YieldReaction ConditionsOperation in experiment
With bromine; triphenylphosphine; In acetonitrile; at 80℃; for 4.0h; (Step 3) Triphenylphosphine (0.94 g) was suspended in acetonitrile (20 ml), bromine (0.19 ml) was added, and the mixture was stirred for 30 min. A solution (10 ml) of <strong>[1021871-35-1]3-chloro-5-(hydroxymethyl)benzonitrile</strong> (0.60 g) obtained in Step 2 in acetonitrile was added to the reaction mixture, and the mixture was stirred at 80°C for 4 hr. The reaction solution was quenched with water, and the mixture was extracted with ethyl acetate. The extract was washed with aqueous sodium hydrogen carbonate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was treated by basic silica gel chromatography (ethyl acetate:hexane=1:2) to give 3-(bromomethyl)-5-chlorobenzonitrile (0.31 g) as a white solid. 1H-NMR (CDCl3) delta ppm 4.42 (2 H, s) 7.58 (2 H, d, J=1.70 Hz) 7.62 (1 H, t, J=1.79 Hz).
With phosphorus tribromide; In dichloromethane; for 1.0h; Toa solution of <strong>[1021871-35-1]5-chloro-3-(hydroxymethyl)benzonitrile</strong> (1.25 g, 7.48 mmol) in DCM(100 mL) was added neat PBr3 (2.43g, 7.48 mmol) and the mixturestirred 1 hr. The mixture was quenched by the addition of saturated NaHC03until the aqueous phase was neutral or slightly basic. The phases wereseparated and the organic phase was washed with brine (20 mL), dried (Na2SC>4),the mixture filtered and the filtrate evaporated to dryness to afford theintermediate bromide as a colourless oil. This was dissolved in acetone (100mL), thioacetic acid (569 mg, 7.48 mmol) and K2C03 (1.55g, 1 1.2 mmol) added and the mixture stirred 1 hr. DCM (100 mL) and saturatedbrine (30 mL) were then added. The phases were separated and the organic phasewas washed with more brine (10 mL), dried (Na2SC>4), the mixturefiltered and the filtrate evaporated to dryness to afford a brown oil,containing the desired title compound (880 mg, 44percent); H NMR (500MHz, CDC13) delta 2.41 (s, 3H), 4.09 (s, 2H), 7.47 - 7.59 (m, 3H).
  • 3
  • [ 1021871-35-1 ]
  • [ 1205513-88-7 ]
YieldReaction ConditionsOperation in experiment
90% With pyridinium chlorochromate; In dichloromethane; at 20℃; for 2.0h;Celite; S-Chloro-S-formyl-benzonitrile: To a stirred solution of 3-Chloro-5-hydroxymethyI- benzonitrile (1.43g, 8.53mmol) in dichloromethane (50ml), were added pyridinium chlorochromate (2.76g, 12.8mmol) and celite (2.76g). After stirring for 2hr. at room temperature, the mixture was diluted with ether and filtered through a plug of silica gel. The plug was washed with ether. The combined filtrate was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, ethyl acetate: hexane (1 :4)) to afford 1.28g (90percent) of a white solid, m.p. 132-133 0C; 1H- NMR(200MHz, CDCI3) delta 7.89(1H, s), 8.05(1H, s), 8.09(1 H, s), 10.02(1H1 s); m/z (El) 165(M+).
  • 4
  • [ 1205513-85-4 ]
  • [ 1021871-35-1 ]
YieldReaction ConditionsOperation in experiment
With ammonium hydroxide; In methanol; S-Chloro-S-hydroxymethyl-benzonitrile: 3-Chloro-5-methyl-benzonitrile (4.19g, 27.64mmoi) in carbon tetrachloride (60ml) was refluxed with N-bromosuccinimide (4.92g, 27 64mmoi) and benzoyl peroxide (669mg, 2.7deltammol) for 5hr. After cooling to room temperature, the mixture was filtered and evaporated in vacuo The residue was purified by silica gel column chromatography (eiuent, ether hexane (from 1 20 to 1 4)) to give 6 84g of S-Bromomethyi-delta-chloro-benzonitrile as a mixture containing starting material. This mixture was stirred with sodium acetate (4.53g, 55.28mmoi) in DMF (50ml) for overnight at room temperature The mixture was diluted with ether, washed with water three times, dried with MgSO4, filtered, and evaporated in vacuo to give Acetic acid 3-chloro-delta-cyano-benzyl ester. The residue was stirred with ammonium hydroxide (10mi) in methanol (40ml). The mixture was then evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, ethyl acetate: hexane (1 :2)) to afford 1.43g (30percent for 3 steps) of S-Chloro-S-hydroxymethyl-benzonitrile as a white solid, m.p. 110-1 1 1 0C; 1H-NMR(200MHz, CDCI3) delta 2.06(1 H, t, J=5.6Hz), 4.74(2H1 d, J=5.6Hz), 7.55(2H, s), 7.61(1 H1 s); m/z (El) 167(M+).
  • 5
  • [ 1021871-35-1 ]
  • 3-chloro-5-cyanobenzyl 4-(2-(N-methyl-1H-1,2,3-triazole-4-carboxamido)ethyl)piperidine-1-carboxylate [ No CAS ]
  • 6
  • [ 1021871-35-1 ]
  • [ 1613514-16-1 ]
  • 7
  • [ 1021871-35-1 ]
  • [ 1613577-16-4 ]
  • 8
  • [ 75-44-5 ]
  • [ 1021871-35-1 ]
  • [ 1613513-55-5 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; toluene; Step 4: 3-Chloro-5-cyanobenzyl carbonochloridate <strong>[1021871-35-1]3-Chloro-5-(hydroxymethyl)benzonitrile</strong> (25 g, 145 mmol) was dissolved in THF (200 mL). The resulting yellow solution was cooled to 10° C. in an ice bath and treated dropwise with phosgene in toluene (152 mL, 289 mmol). The reaction mixture was stirred at ambient temperature for 16 hrs. The mixture was concentrated under reduced pressure and the crude material was diluted with toluene (200 ml) and re-concentrated under reduced pressure. The residue was purified by chromatography on silica (Redisep 340 g column on a Biotage system), eluting with EtOAc/iso-hexane to give 3-chloro-5-cyanobenzyl carbonochloridate as an oil. 1H NMR (600 MHz, CDCl3) delta 7.70 (1H, s), 7.66 (1H, s), 7.62 (1H, s), 5.32 (2H, s).
YieldReaction ConditionsOperation in experiment
62% With sodium tetrahydroborate; ethanol; at 20℃; for 1.0h; General procedure: Toa stirring solution of 4-chloro-3-formylbenzonitrile (5.00 g , 30.2 mmol) inethanol (50 mL), NaBH4 (571 mg, 15.1 mmol) was added batch-wise over 1 minuteunder stirring at room temperature. After 1 hr, the reaction mixture wasconcentrated in vacuo to afford an off-white solid, treated with 2M HC1 (200mL) and DCM (260 mL), effervescence and dissolution occurred. The layers wereseparated, the organic layer was dried over Na2SC>4, the mixturefiltered and concentrated in vacuo to afford the title compound (4.86 g, 96percent)as an off-white solid; H NMR (500 MHz, DMSO) delta 4.58 (d, 2H), 5.63(t, 1H), 7.65 (d, 1H), 7.78 (dd, 1H), 7.85 - 7.94 (m, 1H).
  • 10
  • [ 1021871-35-1 ]
  • 3-[(acetylsulfanyl)methyl]-5-chlorobenzonitrile [ No CAS ]
 

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