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Chemical Structure| 21667-62-9 Chemical Structure| 21667-62-9

Structure of 21667-62-9

Chemical Structure| 21667-62-9

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Product Details of [ 21667-62-9 ]

CAS No. :21667-62-9
Formula : C9H6ClNO
M.W : 179.60
SMILES Code : C1=C(C(CC#N)=O)C=CC=C1Cl
English Name :3-(3-Chlorophenyl)-3-oxopropanenitrile
MDL No. :MFCD00067891
InChI Key :IUDFNNHFARLIPF-UHFFFAOYSA-N
Pubchem ID :140855

Safety of [ 21667-62-9 ]

Computational Chemistry of [ 21667-62-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.11
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 46.2
TPSA ?

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

40.86 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.43
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

2.4
Log Po/w (WLOGP)?

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

2.44
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.

1.66
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

2.65
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.11

Water Solubility

Log S (ESOL):?

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

-2.7
Solubility 0.355 mg/ml ; 0.00198 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.

-2.9
Solubility 0.226 mg/ml ; 0.00126 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

-3.45
Solubility 0.0636 mg/ml ; 0.000354 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.

-5.69 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)

1.27

Application In Synthesis of [ 21667-62-9 ]

* 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 [ 21667-62-9 ]

[ 21667-62-9 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 2905-65-9 ]
  • [ 75-05-8 ]
  • [ 21667-62-9 ]
YieldReaction ConditionsOperation in experiment
43% NaH (0.56 g, 23.44 mmol) was added to a stirred solution of methyl 3- chlorobenzoate (2.0 g, 11.72 mmol) in THF (40 mL) at 0C, and the reaction mixture was heated to 80C. Then MeCN (1.44 g, 35.16 mmol) was added dropwise and the reaction mixture was heated at 80C for 30 min. After completion, THF was removed in vacuo, and the residue was diluted with H2O (100 mL), acidified to pH ~2 with 1N HCl and extracted with EtOAc (3 x 100 mL). Combined organic layers were washed with H2O (50 mL), brine (50 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford 0.9 g of 3-(3-chlorophenyl)-3- oxopropanenitrile as an off-white solid in 43% yield. 0.45 g of the solid was dissolved in 3 mL of MeOH and methyl hydrazine (0.35g, 7.52 mmol) was added. The resulting mixture was heated at 120C for 1 h under microwave. Then MeOH was removed under reduced pressure, and the crude compound was purified by reverse phase column chromatography to afford Int-31 (0.24 g, 46%) as an off-white solid.
  • 2
  • [ 21667-62-9 ]
  • [ 208519-09-9 ]
YieldReaction ConditionsOperation in experiment
94% With hydrazine hydrate In methanol at 150℃; for 0.0833333h; Microwave irradiation; 1.2. General procedure of microwave synthesis of pyrazoles General procedure: A microwave tube was charged with ketonitrile (2.0 mmol), methanol (1 mL), and hydrazine monohydrate (2.6 mmol) and subjected to microwave irradiation (100 W, 150 °C) for 5 minutes. Volatiles were subsequently removed under reduced pressure. The residue was purified by either trituration with cold methanol or cyclohexane, or by using column chromatography to give the final product.
70% With hydrazine In ethanol at 80℃; for 15h; 1 To a stirring solution of 3- (3-clilorophenyl)-3-oxo-propionitrile (2 g, 11.1 mmol) in absolute ethanol (20 mL) was added hydrazine hydrate (3.24 mL, 67 mmol). The reaction mixture was stirred at 80°C for 15 h, cooled to room temperature, concentrated in vacuo, and absorbed on silica gel. Purification on silica gel with 0-10% MeOH in CH2C12 as eluent provided 1.53 g (70%) of 5-(3-chloro-phenyl)-2H-pyrazol-3-ylamine as a green solid. 1H NMR (d6-DMSO) No.: 11. 6 and 11. 9 (2 broad s, 1H, NH+tautomer), 7. 69 (s, 1H), 7.60 (d, 1H), 7. 38 (t, 1H), 7.29 (d, 1H), 5.77 (broad s, 1H), 4.98 (broad s, 2H, NH2). To a stirring solution of 5- (3-chloro-phenyl)-2H-pyrazol-3-ylamine (1.53 g, 7.9 mmol) in THF (32 mL) was added N-bromosuccinimide (1.55 g, 8.7 mmol). The reaction mixture was stirred for 5 h at room temperature, then absorbed on silica gel. Purification on silica gel with 0-10% MeOH in CHzClz as eluent provided 1.73 g (80%) of 4-bromo-5- (3- chloro-phenyl)-2H-pyrazol-3-ylamine as a brown solid. 1H NMR (d6-DMSO) No.: 12.2 and 12.4 (2 broad s, 1H, NH+tautomer), 7.77 (s, 1H), 7.73 (broad s, 1H), 7.48 (broad s, 1H), 7.43 (broad s, 1H), 5.30 (broad s, 1H, NH), 4.82 (broad s, 1H, NH) ; HPLC/MS m/z : 272 [MH3+. To a stirring solution of 4-bromo-5-(3-chloro-phenyl)-2H-pyrazol-3-ylamine (50 mg, 0. 183 mmol) in dioxane (1 mL) was added benzoyl isothiocyanate (27 JIL, 0.202 mmol). The reaction mixture was stirred overnight at 90°C, cooled at room temperature, and partitioned between ethyl acetate and sodium bicarbonate. The organic layer was isolated and absorbed on silica gel. Purification on silica gel with 0-10% MeOH in CH2C12 as eluent provided 10.8mg (17%) ofN [3- (3-chloro-phenyl)-lH-pyrazolo [3, 4-d] thiazol-5-yl]- benzamide as a white solid NMR (d6-DMSO) d : 13.70 and 13.72 (2 broad s, 1H, NH+tautomer), 12.9 (broad s, 1H, NH), 8.12 (d, 2H), 7.81 and 7. 85 (2 broad s, 1H, tautomers), 7.65-7. 74 (m, 2H), 7.54-7. 62 (m, 3H), 7.45 (m, 1H) ; HPLC/MS m/z : 355 [MH] +.
67% With hydrazine hydrate In ethanol for 2h; Heating;
With hydrazine hydrate In ethanol for 5h; Heating;
With hydrazine hydrate In ethanol Reflux;
With hydrazine hydrate In methanol at 160℃; for 0.166667h; Microwave irradiation;

  • 3
  • [ 21667-62-9 ]
  • [ 33906-30-8 ]
  • 2-(3-chlorophenyl)pyrazolo[1,5-a]quinazolin-5(4H)-one [ No CAS ]
  • 4
  • [ 64-17-5 ]
  • [ 21667-62-9 ]
  • [ 62123-73-3 ]
YieldReaction ConditionsOperation in experiment
60% With [bis(acetoxy)iodo]benzene In dichloromethane for 0.5h; Reflux; Ethyl (3-chlorophenyl)glyoxylate 3h General procedure: β-Oxo-benzenepropanenitrile 1(1.0 mmol),PIDA (2.2 mmol) were dissolved in EtOH (8 mL) and stirred under refluxing for 0.5h. After the reaction was completed (monitored by TLC), thereaction mixture was concentrated under vacuum. The residue was purified by chromatographyon silica gel (20:1 petroleum ether/EtOAc) to give the product 3a-o .Thesolvent for the synthesis of 3o was MeOH.
  • 5
  • [ 21667-62-9 ]
  • [ 774178-18-6 ]
YieldReaction ConditionsOperation in experiment
With pyridoxal 5'-phosphate; ω-transaminase from Polaromonas sp. JS666; nitrilase from Hoeflea phototrophica DFL-43; water; 3-amino propanoic acid In aq. phosphate buffer; toluene at 37℃; for 24h; Enzymatic reaction; enantioselective reaction;
  • 6
  • [ 54745-92-5 ]
  • [ 21667-62-9 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Stage #1: 3-chlorobenzoylacetonitrile With sodium hydride In tetrahydrofuran at -5℃; Stage #2: quinoxaline-2-carboxylic acid chloride With benzo<b>thiophene-2-carboxylic acid chloride In tetrahydrofuran at -5 - 25℃; for 13h; 18.B Step B: Preparation of 3-(3-chlorophenyl)-3-hydroxy-2-(quinoxaline-2-carbonyl)propionitrile In a 100mL round-bottom flask, add 20mL of tetrahydrofuran,then add 3-chlorobenzoylacetonitrile (2.0mmol),then add sodium hydride solid (3.5mmol) in batches,in a low-temperature stirrer at -5,stir and react for 10-20min, then dissolve the acyl chloride (2mmol) obtained in the previous step in 5mL of tetrahydrofuran, and slowly drip into the tetrahydrofuran solution of benzoylacetonitrile with a constant pressure dropping funnel, react at -5 for 5min, and then transfer the reaction system to room temperature 25 for 13h. After the reaction is completed, add citric acid to the reaction system to acidify to pH=2, extract with ethyl acetate, dry with anhydrous sodium sulfate, spin dry the solvent, and add silica gel to mix the sample. Use column chromatography (mobile phase solvents are dichloromethane and methanol) to obtain a light yellow solid.
 

Historical Records

Technical Information

• Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blaise Reaction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Catalytic Hydrogenation • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reformatsky Reaction • Ritter Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Ketenes • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Thorpe-Ziegler Reaction • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

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