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Chemical Structure| 2835-98-5 Chemical Structure| 2835-98-5

Structure of Cetilistat Impurity 4
CAS No.: 2835-98-5

Chemical Structure| 2835-98-5

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Product Details of [ 2835-98-5 ]

CAS No. :2835-98-5
Formula : C7H9NO
M.W : 123.15
SMILES Code : OC1=CC(C)=CC=C1N
MDL No. :MFCD00007693
InChI Key :HCPJEHJGFKWRFM-UHFFFAOYSA-N
Pubchem ID :76082

Safety of [ 2835-98-5 ]

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

Computational Chemistry of [ 2835-98-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 2.0
Molar Refractivity 37.84
TPSA ?

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

46.25 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.17
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

1.16
Log Po/w (WLOGP)?

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

1.29
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.

1.15
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

1.11
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.17

Water Solubility

Log S (ESOL):?

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

-1.83
Solubility 1.83 mg/ml ; 0.0149 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.

-1.73
Solubility 2.31 mg/ml ; 0.0188 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

-1.8
Solubility 1.93 mg/ml ; 0.0157 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

No
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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.23 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

2.0 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)

1.0

Application In Synthesis of [ 2835-98-5 ]

* 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 [ 2835-98-5 ]

[ 2835-98-5 ] Synthesis Path-Downstream   1~17

  • 1
  • [ 97-08-5 ]
  • [ 2835-98-5 ]
  • 4-chloro-3-nitro-benzenesulfonic acid-(2-hydroxy-4-methyl-anilide) [ No CAS ]
  • 2
  • [ 2835-98-5 ]
  • [ 14847-51-9 ]
YieldReaction ConditionsOperation in experiment
20% With hydrogen bromide; sodium nitrite;copper(I) bromide; In water; ethyl acetate; A. 2-Bromo-5-methylphenol A solution of sodium nitrite (2.8 g, 41 mmol) in 5 ml water was added rapidly with stirring to an ice-cooled mixture of 6-amino-m-cresol (5.0 g, 41 mmol) and 48% hydrobromic acid (17 ml, 100 mmol). The temperature was kept below 10 C. by addition of ice chips. The diazonium salt solution was then added in portions over a period of 30 min to a boiling mixture of copper(I) bromide (6.4 g, 22 mmol) and 48% hydrobromic acid (5 ml). The resulting mixture was refluxed for an additional 30 min, then was cooled and extracted with ether (2*100 ml). The combined organic extracts were washed with water, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel using 98:2 hexanes/ethyl acetate to afford 233A (1.6 g, 20%) as an oil.
  • 3
  • [ 2835-98-5 ]
  • [ 530-62-1 ]
  • [ 22876-16-0 ]
YieldReaction ConditionsOperation in experiment
90% In acetonitrile; at 23 - 70℃; To a solution of 2-amino-5-methylphenol (777 mg, 6.32 mmol) in acetonitrile (27 mL) at 23 C. was added 1,1'-carbonyldiimidazole (3.07 g, 18.9 mmol) and the reaction mixture was heated to 70 C., and stirred overnight. The reaction mixture was cooled to room temperature and partitioned between ethyl acetate (150 mL) and H2O (100 mL). The organic layer was separated and washed with brine (100 mL), dried (MgSO4) and concentrated to yield the crude product which was purified by silica gel column chromatography (20-50% EtOAc in hexanes) to yield 6-methyl-3H-benzooxazol-2-one (853 mg, 90%).
In dichloromethane; at 20℃; for 24h;Inert atmosphere; General procedure: To a solution of the corresponding 2-amino phenol (1 equiv.) in dry dichloromethane was added 1,1’,-dicarbonyldiimidazole (1.1 equiv) and stirred at ambient temperature under a nitrogen atmosphere for 24 h. The reaction mixture was quenched with water and extracted with ethyl acetate (3x). The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The benzoxazolone residue was purified by silica gel chromatography.
  • 5
  • [ 792-74-5 ]
  • [ 2835-98-5 ]
  • C28H20N2O2 [ No CAS ]
  • 6
  • [ 792-74-5 ]
  • [ 2835-98-5 ]
  • biphenyl-4,4'-dicarboxylic acid bis-[(2-hydroxy-4-methyl-phenyl)-amide] [ No CAS ]
  • 7
  • [ 2835-98-5 ]
  • [ 22876-16-0 ]
  • 8
  • [ 32315-10-9 ]
  • [ 2835-98-5 ]
  • [ 22876-16-0 ]
YieldReaction ConditionsOperation in experiment
83% With triethylamine; In tetrahydrofuran; at 0 - 20℃; A solution of triphosgene (1.93g, 6.5mmol) in anhydrous THF (40mL) was added to a solution of 2-amino-5-methylphenol (10g, 8.1mmol) and Et3N (2.3mL) in anhydrous THF (40mL) at 0C. The resulting solution was stirred at room temperature (RT) for overnight and was diluted with water (10mL). After 30min, the reaction mixture was concentrated in vacuo and the residue was extracted with ethyl acetate (50mL×3). The combined organic layer was washed by saturated sodium chloride solution for three times, dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford 6-methylbenzo[d]oxazol-2(3H)-one as an off-white solid. Yield 83% (1.93g). MS (ESI): 150.1 [M+H]+
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0℃;Inert atmosphere; Synthesis of 3-benzyl-6-methyl-3H-benzooxazol-2-one (2)A solution of 2-amino-5-methyl-phenol (1.0 gm, 8.1 mmol) in CH2Cl2 (30 ml) was cooled to 0 0C. Triphosgene (721 mg, 2.43 mmol) was added followed by diisopropylethylamine (7.0 ml, 17.6 mmol) and the reaction mixture was stirred under nitrogen atmosphere for 2 h. The reaction mixture was washed with water and brine. The organic phase was dried over anhydrous MgSO4 and evaporated under vacuum. The crude product 6- methylbenzo[d]oxazol-2(3H)-one was used for the next step without any purification.
  • 9
  • [ 2835-98-5 ]
  • [ 7693-46-1 ]
  • [ 22876-16-0 ]
  • 10
  • [ 2835-98-5 ]
  • [ 135636-66-7 ]
  • [ 155601-65-3 ]
  • [ 1360427-70-8 ]
YieldReaction ConditionsOperation in experiment
68% A mixture of <strong>[155601-65-3]2,6-difluoronicotinaldehyde</strong> (2 g, 13.9 mmol), 2-amino-5-methylphenol (1.7 g, 13.8 mmol) and 2,3-butanedione monoxime (1.065 g, 10.5 mnol) in acetic acid (120 mL) was heated at 120 C for 1.5 hours. After cooling down to room temperature, zinc powder (2 g) was added and the mixture heated one hour at 120 C and left overnight at room temperature. The suspension is then filtered and filtrate is reduced to about 20 mL. Water was added (about 100 mL) and aqueous KOH was added up to pH ~ 8. The mixture was extracted with dichloromethane and the crude obtained purified by column chromatography using CH2Cl2/Et2O as eluent. The ligand was obtained as a beige solid (2.14 g, yield 68 %) 1H NMR (CDCl3, 400 MHz): delta 8.28 (t, J= 8.0 Hz, 1H); 7.25 (d, J= 1.6 Hz, 1H); 7.09 (d, J= 8.4 Hz, 1H); 6.99 (ddd, J= 8.0, 2.0, 0.8 Hz, 1H); 6.79 (dd, J= 8.4, 2.8 Hz, 1H); 2.27 (s, 3H); 2.24 (d, J= 0.8 Hz, 3H); 2.19 (d, J= 0.8 Hz, 3H).
68% <strong>[155601-65-3]2,6-difluoronicotinaldehyde</strong> was obtained as described in M. Schlosser and T. Rausis, Eur. J. Org. Chem. 2004, 1018.A mixture of <strong>[155601-65-3]2,6-difluoronicotinaldehyde</strong> (2 g, 13.9 mmol), 2-amino-5- methylphenol (1.7 g, 13.8 mmol) and 2,3-butanedione monoxime (1.065 g, 10.5 mmol) in acetic acid (120 mL) was heated at 120C for 1.5 hours. After cooling down to room temperature, zinc powder (2 g) was added and the mixture heated one hour at 120C and left overnight at room temperature. The suspension is then filtered and filtrate is reduced to about 20 mL. Water was added (about 100 mL) and aqueous KOH was added up to pH ~ 8. The mixture was extracted with dichloromethane and the crude obtained purified by column chromatography using CH2Cl2/Et20 as eluent. The ligand was obtained as a beige solid (2.14 g, yield 68 %).1H MR (CDC13, 400 MHz) : delta 8.28 (t, J= 8.0 Hz, IH) ; 7.25 (d, J= 1.6 Hz, IH) ; 7.09 (d, J= 8.4 Hz, IH) ; 6.99 (ddd, J= 8.0, 2.0, 0.8 Hz, IH) ; 6.79 (dd, J= 8.4, 2.8 Hz, IH) ; 2.27 (s, 3H) ; 2.24 (d, J= 0.8 Hz, 3H) ; 2.19 (d, J= 0.8 Hz, 3H).
  • 11
  • [ 201230-82-2 ]
  • [ 2835-98-5 ]
  • [ 22876-16-0 ]
  • 12
  • [ 201230-82-2 ]
  • [ 38573-88-5 ]
  • [ 2835-98-5 ]
  • 4-fluoro-7-methyldibenzo[b,f][1,4]oxazepin-11(10H)-one [ No CAS ]
  • 13
  • [ 17282-03-0 ]
  • [ 201230-82-2 ]
  • [ 2835-98-5 ]
  • 3,9-dimethylbenzo[b]pyrido[3,2-f ][1,4]oxazepin-5(6H)-one [ No CAS ]
  • 14
  • [ 6624-49-3 ]
  • [ 2835-98-5 ]
  • 2-(3-isoquinolinyl)-6-methylbenzoxazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With polyphthalamide(PPA); at 100 - 180℃; for 4h;Inert atmosphere; Under the system the protection of nitrogen, the dimethyl amide (PPA) 25mmol such, is placed in the reaction system, the temperature to a 100 °C the rear, the <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> 25mmol, 6-amino-m-cresol 25mmol, added to the above-mentioned reaction solution at the same time, continue to heating to 180 °C, reaction 4 hours, to be after the reaction cooling, dichloromethane is used for extraction, using rotary evaporimeter evaporation of the solvent, to obtain 2 - (3-isoquinolyl) - 6-benzoxazole (A-1) 15.75mmol, the yield is 63percent.
  • 15
  • [ 2835-98-5 ]
  • [ 51012-64-7 ]
  • (3SR,3a'SR,8a'RS)-2',6',7-trimethyl-3a',8a'-dihydro-1'H,2H,4H-spiro[benzo[b][1,4]oxazine-3,8'-indeno[1,2-c]pyrrole]-1',3'(2'H)-dione [ No CAS ]
  • 16
  • [ 2835-98-5 ]
  • [ 51012-64-7 ]
  • 7-methyl-3-(m-tolyl)-2H-benzo[b][1,4]oxazine [ No CAS ]
  • 17
  • [ 15226-74-1 ]
  • [ 17282-03-0 ]
  • [ 2835-98-5 ]
  • 3,9-dimethylbenzo[b]pyrido[3,2-f ][1,4]oxazepin-5(6H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In N,N-dimethyl-formamide; at 135℃; for 12h;Sealed tube; Inert atmosphere; General procedure: Method A: A sealed tube equipped with a magnetic stir bar was charged with the corresponding 3-bromo-2-fluoropyridine (1 mmol), amino phenol (1 mmol), Pd(OAc)2 (5 mol%), xantphos (5 mol%) and DMAP (2.5 mmol). The tube was purged with argon. Then DMF (10V) was added followed by the addition of Co2(CO)8 (0.25 mmol). The tube was closed with seal plug instantly. The reaction tube was placed in a preheated oil bath at 120 0C for 8 h. On completion, the reaction mixture was cooled to room temperature, added water and ethyl acetate (1:1). Precipitated solid was filtered through a Celite bed. The bed was washed thoroughly with ethyl acetate. Organic layer was separated. Aqueous layer extracted with EtOAc. The combined organic layers were washed with water, brine, dried over anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure and purified by flash column chromatography on silica gel (230-400 mesh) with ethyl acetate and petroleum ether as eluent to afford the corresponding pyridobenzoxazepinone. Method B: A sealed tube equipped with a magnetic stir bar was charged with the corresponding 3-bromo-2-chloropyridine (1 mmol), amino phenol (1 mmol), Pd(OAc)2 (5 mol%), xantphos (5 mol%) and DBU (2.5 mmol). The tube was purged with argon. Then DMF (10 V) was added followed by the addition of Co2(CO)8 (0.25 mmol). The tube was closed with seal plug instantly. The reaction tube was placed in a pre heated oil bath at 135 0C for 12 h. On completion, the reaction mixture was cooled to room temperature, added water and ethyl acetate (1:1). Precipitated solid was filtered through a Celite bed. The bed was washed thoroughly with ethyl acetate. Organic layer was separated. Aqueous layer extracted with EtOAc. The combined organic layers were washed with water, brine, dried over anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure and purified by flash column chromatography on silica gel (230-400 mesh) with ethyl acetate and petroleum ether as eluent to afford the corresponding pyridobenzoxazepinone.
 

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