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Chemical Structure| 18698-99-2 Chemical Structure| 18698-99-2

Structure of (2-Cyanophenyl)acetic acid
CAS No.: 18698-99-2

Chemical Structure| 18698-99-2

(2-Cyanophenyl)acetic acid

CAS No.: 18698-99-2

4.5 *For Research Use Only !

Cat. No.: A122548 Purity: 97%

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Product Details of [ 18698-99-2 ]

CAS No. :18698-99-2
Formula : C9H7NO2
M.W : 161.16
SMILES Code : O=C(O)CC1=CC=CC=C1C#N
MDL No. :MFCD01646238
InChI Key :QLHZKPQKYARBGT-UHFFFAOYSA-N
Pubchem ID :87755

Safety of [ 18698-99-2 ]

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

Computational Chemistry of [ 18698-99-2 ] 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 3.0
Num. H-bond donors 1.0
Molar Refractivity 42.7
TPSA ?

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

61.09 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.26
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

1.12
Log Po/w (WLOGP)?

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

1.19
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.

1.02
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

1.53
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.22

Water Solubility

Log S (ESOL):?

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

-1.78
Solubility 2.66 mg/ml ; 0.0165 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-2.0
Solubility 1.63 mg/ml ; 0.0101 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

-2.25
Solubility 0.904 mg/ml ; 0.00561 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.

-6.49 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.

0.56

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)

1.65

Application In Synthesis of [ 18698-99-2 ]

* 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 [ 18698-99-2 ]

[ 18698-99-2 ] Synthesis Path-Downstream   1~33

  • 1
  • [ 186581-53-3 ]
  • [ 18698-99-2 ]
  • [ 20921-96-4 ]
  • 2
  • [ 3342-78-7 ]
  • [ 18698-99-2 ]
  • 3
  • [ 18698-99-2 ]
  • [ 55086-26-5 ]
  • 4
  • [ 3342-78-7 ]
  • [ 151-50-8 ]
  • [ 18698-99-2 ]
  • 7
  • [ 18698-99-2 ]
  • [ 117197-16-7 ]
YieldReaction ConditionsOperation in experiment
69% Compound V (5.00 g, 0.031 mol) was dissolved in dry dichloromethane (150 mL). Afterwards, oxalylchloride (5.25 mL, 0.062 mol) was added, followed by a catalytic amount of Nu,Nu-dimethylformamide (about 0.05 mL). The mixture was then stirred at room temperature under an inert atmosphere for 70 minutes and evaporated to dryness. The oily residue was dissolved in dry tetrahydrofuran (THF) (50 mL) and added to an aqueous ammonia (26percent, 100 mL) cooled in an ice-water bath. The mixture was stirred at 0-5 °C for 20 minutes and then additional 40 minutes at room temperature. After the reaction was completed, the mixture was poured into a separation funnel and extracted by EtOAc (2 x 250 mL). The combined organic extracts were washed with saturated NaHC03 solution (2 x 100 mL), dried over MgS04 and evaporated to dryness. The crude product was crystallized from z'PrOH/hexane to give the title compound as an off- white solid (3.41 g, 69percent).
  • 8
  • [ 18698-99-2 ]
  • 2-(2-Cyano-phenyl)-N,N-dimethyl-acetamide [ No CAS ]
  • 9
  • 1-chloro-3-hydroxyquinoline [ No CAS ]
  • [ 3740-52-1 ]
  • [ 18698-99-2 ]
YieldReaction ConditionsOperation in experiment
palladium on charcoal; In aq.sodium hydroxide; (2E/Z, 4E)-N-Isobutyl 3-methyl-12-(1-chloro-3-isoquinolinyloxy)dodeca-2,4-dienamide Starting from 1-chloro-3-hydroxyquinoline and using the modified Stage a of Example CII 2-Nitrophenylacetic acid (ex Aldrich) (18.1 g) dissolved in 0.1M.aq.sodium hydroxide (100 ml) was subjected to catalytic hydrogenation (at 30-40 psi) over 10percent palladium on charcoal (2 g) until uptake ceased. The resultant solution was subjected first to diazotisation and then reaction with sodium cyanide and cuprous cyanide according to Simchen and Hafner, Ann. Chem., 1974, 1802 to give crude 2-cyanophenylacetic acid (14.9 g).
  • 10
  • [ 18698-99-2 ]
  • [ 62-53-3 ]
  • N-phenyl-2-(2-cyanophenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% Compound V (50.0 g, 0.310 mol) was charged to a 1 L jacketed reactor and suspended in dry ethyl acetate (700 mL). Thionyl chloride (27.2 mL, 0.372 mol) was added in one portion and the mixture was then heated at 45 °C for 2 hours. The mixture was then concentrated at a temperature 40-50 °C and reduced pressure (50- 200 mbar) to a volume of approximately 600 mL. Afterwards, the residue was cooled to 0 °C , followed by addition of aniline (62.2 mL, 0.682 mol) dissolved in ethyl acetate (150 mL). The rate of the addition was controlled to keep the temperature of the reaction mixture below 25 °C. After the addition was finished, the mixture was stirred at room temperature for 30 minutes, followed by addition of 2.5percent aqueous NaCl (200 mL) and heating the obtained mixture to 40-45°C with stirring. When all of the solid material was dissolved, the water phase was separated. The solvent in the remaining phase was replaced by isopropanol (iPrOH) by adding and evaporating of iPrOH in several portions (4 x 100 mL), then the mixture was concentrated at 40- 45 °C under reduced pressure (50-200 mbar) to a volume of approximately 400 mL, followed by addition of water (200 mL). The mixture was cooled to 0 °C, stirred at the same temperature for 30 minutes and filtered. The obtained product was then washed with 50percent aqueous iPrOH (180 mL) and dried in an inert atmosphere at room temp overnight to give compound Ill-a as an off- white solid (67.1 g, yield 92percent>) with a HPLC purity of ~92percent>. The product was analyzed by PXRD, and the PXRD pattern is shown in Figure 4.
  • 11
  • [ 18698-99-2 ]
  • [ 62-53-3 ]
  • [ 380917-97-5 ]
  • 12
  • [ 18698-99-2 ]
  • [ 380917-97-5 ]
  • 13
  • [ 18698-99-2 ]
  • [ 380917-96-4 ]
  • 14
  • [ 18698-99-2 ]
  • ethyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(1,2,3,3a,4,8b-hexahydroindeno[1,2-b]pyrrol-7-yl)propanoate hydrochloride [ No CAS ]
  • 3-{1-[2-(2-cyanophenyl)acetyl]-1H,2H,3H,3aH,4H,8bH-indeno[1,2-b]pyrrol-7-yl}-3-(1,4-dimethyl-1H-1,2,3-benzotriazol-5-yl)propanoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% To a solution of ethyl 3-(1 ,4-dimethyl-1 H-benzo[d][1 ,2,3]triazol-5-yl)-3-(1 ,2,3,3a,4,8b- hexahydroindeno[1,2-b]pyrrol-7-yl)propanoate, hydrochloride (50 mg, 0.113 mmol) in DCM (2mL) was added <strong>[18698-99-2]2-(2-cyanophenyl)acetic acid</strong> (21.93 mg, 0.136 mmcl), TEA (0.063 mL, 0.454 mmcl) and then T3P (50percent wt in EtOAc) (0.101 mL, 0.170 mmcl). The resulting reaction mixture was stirred at ambient temperature for 30 mm. The reaction mixture was concentrated under reduced pressure and dissolved in methanol (2.000 mL) after which was added NaOH (3 N)(0.378 mL, 1.134 mmol). The resulting reaction mixture was heated with microwave at 100 C for 20 mm. The reaction mixture was acidified with HCI (3 N) to pH 34 then concentrated under reduced pressure, and purified with reverse phase HPLC to afford the desired product 3-(1 -(2- (2-cyanophenyl)acetyl)-1 ,2,3,3a,4,8b-hexahydroindeno[1 ,2-b]pyrrol-7-yl)-3-(1 ,4-dimethyl-1 Hbenzo[d][1 ,2,3]triazol-5-yl)propanoic acid (32.4 mg, 0.062 mmol, 55.0 percent yield). LC-MS m/z520.3 (M+H), 0.90 mm (ret. time).
55.0% To a solution of ethyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(1,2,3,3a,4,8b- hexahydroindeno[1,2-b]pyrrol-7-yl)propanoate, hydrochloride (50 mg, 0.113 mmol) in DCM (2 mL) was added <strong>[18698-99-2]2-(2-cyanophenyl)acetic acid</strong> (21.93 mg, 0.136 mmol), TEA (0.063 mL, 0.454 mmol) and then T3P (50percent wt in EtOAc) (0.101 mL, 0.170 mmol). The resulting reaction mixture was stirred at ambient temperature for 30 min. The reaction mixture was concentrated under reduced pressure and dissolved in methanol (2.000 mL) after which was added NaOH (3 N) (0.378 mL, 1.134 mmol). The resulting reaction mixture was heated with microwave at 100°C for 20 min. The reaction mixture was acidified with HCl (3 N) to pH 34 then concentrated under reduced pressure, and purified with reverse phase HPLC to afford the desired product 3-(1-(2- (2-cyanophenyl)acetyl)-1,2,3,3a,4,8b-hexahydroindeno[1,2-b]pyrrol-7-yl)-3-(1,4-dimethyl-1H- benzo[d][1,2,3]triazol-5-yl)propanoic acid (32.4 mg, 0.062 mmol, 55.0 percent yield). LC-MS m/z 520.3 (M+H)+, 0.90 min (ret. time).
  • 15
  • [ 18698-99-2 ]
  • [ 1395030-58-6 ]
  • 16
  • [ 18698-99-2 ]
  • C30H30N8O3 [ No CAS ]
  • 17
  • [ 18698-99-2 ]
  • C31H31N7O3 [ No CAS ]
  • 18
  • [ 18698-99-2 ]
  • [ 1092794-06-3 ]
  • 19
  • [ 18698-99-2 ]
  • [ 1092794-08-5 ]
  • 20
  • [ 18698-99-2 ]
  • [ 1092794-09-6 ]
  • C11H10N2O3 [ No CAS ]
  • 21
  • [ 18698-99-2 ]
  • [ 561297-87-8 ]
  • C11H12N2O2 [ No CAS ]
  • 22
  • [ 18698-99-2 ]
  • [ 1092794-10-9 ]
  • 23
  • [ 18698-99-2 ]
  • [ 1092794-11-0 ]
  • 24
  • [ 18698-99-2 ]
  • C13H16N2O [ No CAS ]
  • 25
  • [ 18698-99-2 ]
  • C13H14F2N2O2 [ No CAS ]
  • 26
  • [ 18698-99-2 ]
  • [ 18107-18-1 ]
  • [ 20921-96-4 ]
YieldReaction ConditionsOperation in experiment
95% In tetrahydrofuran; methanol; at 15 - 30℃; for 2h; Compound 10.1 (5 g, 31 mmol) And (trimethylsilane) diazomethane (3.5 g, 31 mmol) Tetrahydrofuran (20mL) The mixed solution with methanol (20 mL) was stirred at room temperature for 2 hours. Then the reaction system is directly concentrated, The residue was chromatographed on silica gel (30percent ethyl acetate petroleum ether) Purification afforded compound 10.2 (5.1 g, yield: 95percent) as a colourless oil.
  • 27
  • [ 18698-99-2 ]
  • [ 822-67-3 ]
  • C15H15NO2 [ No CAS ]
  • 28
  • [ 18698-99-2 ]
  • [ 58329-99-0 ]
  • C14H15N [ No CAS ]
  • C14H15N [ No CAS ]
  • 29
  • [ 104-54-1 ]
  • [ 18698-99-2 ]
  • C17H15N [ No CAS ]
  • 30
  • [ 104-54-1 ]
  • [ 18698-99-2 ]
  • C18H15NO2 [ No CAS ]
  • 31
  • [ 18698-99-2 ]
  • [ 124517-47-1 ]
  • C17H15N [ No CAS ]
  • 32
  • [ 201230-82-2 ]
  • [ 22115-41-9 ]
  • [ 18698-99-2 ]
YieldReaction ConditionsOperation in experiment
61% With cobalt(II) pyridine-2-carboxylate; palladium diacetate; sodium hydroxide; In methanol; at 150℃; under 11251.1 Torr; for 6h;Autoclave; 312 ml of methanol, 0.55 g of cobalt pyridine-2-carboxylate,1.37 g of palladium acetate was added to the autoclave reactor.The catalyst was dissolved by stirring for 5 minutes, and the air in the kettle was replaced with CO three times, and the temperature was raised to 150 ° C.Rush into the CO until the pressure rises to 1.5 MPa. Within 1 hour,At the same time, 78.4 g (0.4 mol) of o-cyanobenzyl bromide and 30percent of NaOH 160 g (1.2 mol) were added dropwise to the reaction vessel.After reacting for 5 hours, the temperature was lowered to room temperature, methanol was removed by distillation under reduced pressure, and the catalyst was filtered off.Add 30percent hydrochloric acid to adjust the pH to 1, filter,Dry to obtain o-cyanophenylacetic acid, the purity is:98.56percent, the yield was 61percent.
  • 33
  • [ 18698-99-2 ]
  • 4'-amino-2',6'-dichloro-4-isobutyl-[1,1'-biphenyl]-3-carbonitrile [ No CAS ]
  • 2-(2-Cyanophenyl)-N-(2,6-dichloro-3'-cyano-4'-isobutyl-[1,1'-biphenyl]-4-yl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
83.3% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; Example 11 2-(2-Cyanophenyl)-N-(2,6-dichloro-3'-cyano-4'-isobutyl-[1,1'-biphenyl]-4-yl)acetamide The method is the same as in Example 1. 4'-Amino-2',6'-dichloro-4-isobutyl-[1,1'-biphenyl]-3-carbonitrile (50 mg, 0.16 mmol), <strong>[18698-99-2]2-(2-cyanophenyl)acetic acid</strong> (30 mg, 0.19 mmol), HATU (72 mg, 0.19 mmol), N,N-diisopropylethylamine (62 mg, 0.48 mmol) and dichloromethane (2 mL) were reacted at room temperature overnight, and the crude product was separated by a silica gel column (petroleum ether: ethyl acetate =1:1) to give a product (white solid, 60 mg), with a yield of 83.3%. 1H NMR (400 MHz, CDCl3) delta 7.86 (d, J = 54.7 Hz, 1H), 7.71 (d, J = 7.7 Hz, 1H), 7.68 (s, 2H), 7.64 (d, J = 7.4 Hz, 1H), 7.60 (d, J = 7.7 Hz, 1H), 7.51 - 7.41 (m, 2H), 7.35 (s, 2H), 3.96 (s, 2H), 2.77 (d, J = 7.3 Hz, 2H), 2.11 - 1.99 (m, 1H), 0.99 (d, J = 6.5 Hz, 6H). MS (ESI) m/z: 462.0 (M+1).
 

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