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Structure of 6919-61-5

Chemical Structure| 6919-61-5

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Product Details of [ 6919-61-5 ]

CAS No. :6919-61-5
Formula : C9H11NO2
M.W : 165.19
SMILES Code : O=C(N(OC)C)C1=CC=CC=C1
MDL No. :MFCD00075320
InChI Key :UKERDACREYXSIV-UHFFFAOYSA-N
Pubchem ID :569575

Safety of [ 6919-61-5 ]

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

Computational Chemistry of [ 6919-61-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 45.42
TPSA ?

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

29.54 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.13
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

0.67
Log Po/w (WLOGP)?

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

1.32
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.

1.78
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

0.8
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.34

Water Solubility

Log S (ESOL):?

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

-1.46
Solubility 5.75 mg/ml ; 0.0348 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.

-0.87
Solubility 22.4 mg/ml ; 0.136 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

-2.19
Solubility 1.07 mg/ml ; 0.00647 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.

-6.83 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)

1.36

Application In Synthesis of [ 6919-61-5 ]

* 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 [ 6919-61-5 ]

[ 6919-61-5 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 6919-61-5 ]
  • [ 1826-67-1 ]
  • [ 103-67-3 ]
  • [ 21970-65-0 ]
  • 2
  • [ 18207-47-1 ]
  • [ 500719-87-9 ]
  • [ 6919-61-5 ]
  • 2,4-Di-furan-2-yl-5-[2,2,2-trifluoro-eth-(Z)-ylidene]-2,4-bis-trifluoromethyl-[1,3]dioxolane [ No CAS ]
  • 3
  • [ 6919-61-5 ]
  • [ 70298-89-4 ]
  • [ 125867-35-8 ]
  • 4
  • [ 1513-65-1 ]
  • [ 6919-61-5 ]
  • [ 1158955-21-5 ]
YieldReaction ConditionsOperation in experiment
Reference Example 30; (2,6-Difluoropyridin-3-yl)(phenyl)methanoneTo a solution of 2,6-difluoropyridine (1.0 g, manufactured by Tokyo Chemical Industry Co., Ltd.) in tetrahydrofuran (40 mL, manufactured by Kanto Chemical Co., Inc.), lithium diisopropylamide (23% solution in tetrahydrofuran/ethylbenzene/heptane, 5.79 mL, manufactured by Sigma-Aldrich Corp.) was added dropwise at -78 C., and the mixture was stirred for 30 minutes. Subsequently, N-methoxy-N-methylbenzamide (1.46 mL, manufactured by Sigma-Aldrich Corp.) was further added at the same temperature, and while the temperature was gradually raised to room temperature, the mixture was stirred overnight. A saturated aqueous solution of ammonium chloride (30 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (3×30 mL), washed with brine (30 mL), and dried (MgSO4). The solvent was then evaporated, to give 1.90 g of the title compound. LC-MS: HPLC retention time 1.63 minutes, m/z (M-F+OMe) 232, condition C-1.
  • 5
  • [ 108-89-4 ]
  • [ 6919-61-5 ]
  • [ 1620-55-9 ]
YieldReaction ConditionsOperation in experiment
70% -Phenyl-2-(pyridin-4-yl)ethanone (2): Lithium diisopropyl amide (16.9 mL, 1.5 M in cyclohexane, 25.4 mmol) was added to THF (40 mL) at -78 0C. A solution of 4-picoline (2.50 mL, 25.4 mmol) in THF (30.0 mL) was added dropwise to the LDA solution. The dry ice bath was removed. The reaction mixture was stirred at 0 C for 30 minutes, and cooled down to -78 "C. A solution of N-methoxy-N- methylbenzamide (1) (5.00 g, 29.6 mmol) in THF (20.0 mL) was added dropwise. The reaction mixture was warmed to room temperature and stirred overnight. The mixture was quenched with water, and extracted with ethyl acetate (3x). The pooled organic layer was dried over magnesium sulfate. The mixture was filtered, and the solvent was removed under vacuum to give the crude product. The crude material was triturated with hot hexane, and filtered to give l-phenyl-2-(pyridin-4-yl)ethanone (2) as a yellow solid (3.53 g, 17.9 mmol, 70% yield).
70% l-Phenyl-2-(pyridin-4-yl)ethanone (2): Lithium diisopropyl amide (16.9 mL, 1.5 M in cyclohexane, 25.4 mmol) was added to THF (40 mL) at -78 0C. A solution of 4- picoline (2.50 mL, 25.4 mmol) in THF (30.0 mL) was added dropwise to the LDA solution. The dry ice bath was removed. The reaction mixture was stirred at 0 0C for 30 minutes, and cooled down to -78 0C. A solution of N-methoxy-N-methylbenzamide (1) (5.00 g, 29.6 mmol) in THF (20.0 mL) was added dropwise. The reaction mixture was warmed to room temperature and stirred overnight. The mixture was quenched with water, and extracted with ethyl acetate (3x). The pooled organic layer was dried over magnesium sulfate. The mixture was filtered, and the solvent was removed under vacuum to give the crude product. The crude material was triturated with hot hexane, and filtered to give l-phenyl-2-(pyridin-4-yl)ethanone (2) as a yellow solid (3.53 g, 17.9 mmol, 70% yield).
To a stirred solution of lithium diisopropylamide (1.5 eq) in THF at -78 C. a solution of 4-picoline (1 eq) in THF is added slowly. After 15 min, a solution of N-methoxy-N-methylbenzamide (1.2 eq) in THF is added. The reaction mixture is allowed to warm to ambient temperature. The formation of product is monitored by HPLC. The reaction mixture is poured into a saturated aqueous sodium bicarbonate solution, then extracted with ethylacetate. The organic phase is washed with brine, dried over anhydrous magnesium sulphate and evaporated under reduced pressure to give the crude product. The crude product is then purified by flash column chromatography (25-100% EtOAc-hexane) to give the product ketone 2. Purity >90%, ESI m/z 198.18 (MH+).
THF in a round bottom flask was cooled (-78 C), lithium diisopropylamide added to the flask with stirring under argon atmosphere, and a solution of 4-picoline (in THF) carefully added to the cooled flask under constant stirring. After one hour, a solution ofN-methoxy-N-methylbenzamide (in THF) was added over a period of 30 min. Formation of the product was monitored by HPLC and TLC. The reaction mixture was warmed to ambient temperature, during which time the color changed from light yellow to orange, and the reaction quenched with crushed ice addition. THF was removed in vacuo, the reaction mixture was treated with saturated sodium bicarbonate solution, and repeat extraction with ethyl acetate was done in a separately funnel The combined organic extracts were treated with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to yield an oily mixture. The crude mixture was purified by column chromatography on silica gel (200-400 mesh) with product elution using ethyl acetate: hexane (1 :4 v/v). The product, ketone 2-1, was obtained as a bright yellow solid in 69% (gravimetric) yield, 90% purity by HPLC and a mass (ESI) oim/z (MeOH) = 198.18 (MH ).

  • 6
  • [ 24134-09-6 ]
  • [ 6919-61-5 ]
  • [ 235092-29-2 ]
YieldReaction ConditionsOperation in experiment
44% To a solution of 5-bromo-1 ,2-dimethyl-1H-imidazole (10.0 g, 57.1 mmol) in dichloromethane (50 ml_) was added dropwise ethylmagnesium bromide (3 M in Et2O, 19.0 ml_, 57.0 mmol). After stirring at room temperature for 30 min, the reaction mixture was cooled down to 0C with an <n="114"/>ice-brine bath and N-Methoxy-N-methyl-benzamide (8.70 ml_, 57.1 mmol) was added dropwise. The mixture was stirred for 7.5h at room temperature. The mixture was worked-up by addition of water (100 ml_), then acidified with aq. HCI (1 M) until pH = 7. After extraction with dichloromethane (2 x 75 ml_), the organic layers were washed with water (2 x 100 ml_) then dried over MgSO4 and concentrated in vacuo. Purification of the residue on silica gel afforded (1 ,2-dimethyl-1H-imidazol-5-yl)(phenyl)methanone [8.41 g, yield 44% ; HPLC/MS : m/z = 201 (M+H) ; logP(HcooH) = 0.56].
  • 7
  • [ 66217-56-9 ]
  • [ 6919-61-5 ]
  • [ 6008-36-2 ]
 

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