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Structure of 5896-17-3

Chemical Structure| 5896-17-3

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Product Details of [ 5896-17-3 ]

CAS No. :5896-17-3
Formula : C14H12O2
M.W : 212.24
SMILES Code : O=CC1=CC=CC=C1OCC2=CC=CC=C2
MDL No. :MFCD00016583
InChI Key :PBEJTRAJWCNHRS-UHFFFAOYSA-N
Pubchem ID :344784

Safety of [ 5896-17-3 ]

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

Computational Chemistry of [ 5896-17-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 12
Fraction Csp3 0.07
Num. rotatable bonds 4
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 62.81
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.39
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

3.21
Log Po/w (WLOGP)?

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

2.93
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.

2.6
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

3.57
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.94

Water Solubility

Log S (ESOL):?

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

-3.47
Solubility 0.072 mg/ml ; 0.000339 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.

-3.43
Solubility 0.078 mg/ml ; 0.000368 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

-5.01
Solubility 0.00205 mg/ml ; 0.00000966 mol/l
Class?

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

Moderately 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

Yes
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

Yes
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.

-5.32 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

0.0
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)

1.74

Application In Synthesis of [ 5896-17-3 ]

* 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 [ 5896-17-3 ]

[ 5896-17-3 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 5896-17-3 ]
  • [ 3381-87-1 ]
YieldReaction ConditionsOperation in experiment
98% With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 0.666667h; To a solution of 2-benzyloxybenzaldehyde (1.00 g, 4.71 mmol, 1.0 equiv) in MeOH (25 mL) at 0 C. was added NaBH4 (0.40 g, 9.43 mmol, 2.0 equiv) portionwise over 10 minutes. After gas evolution ceased, the reaction mixture was warmed to room temperature and stirred for 30 minutes. The reaction was concentrated and the residue partitioned between H2O (50 mL) and EtOAc (50 mL). The organic phase was separated and the aqueous phase extracted with EtOAc (2×75 mL). The combined organic extracts were dried (Na2SO4) then concentrated to afford the title compound (0.98 g, 98%), which required no further purification. 1H NMR (600 MHz, CDCl3) δ 2.22 (br s, 1H), 4.73 (s, 2H), 5.12 (s, 2H), 6.92-7.00 (m, 2H), 7.24-7.29 (m, 1H), 7.29-7.37 (m, 2H), 7.37-7.44 (m, 4H). 13C NMR (150 MHz, CDCl3) δ62.4, 70.3, 111.9, 121.3, 127.6, 128.4, 129.0, 129.1, 129.2, 129.8, 137.0, 156.9.
90% With sodium tetrahydroborate; In methanol; at 0℃; for 0.5h; General procedure: NaBH4 (50 mg, 1.3 mmol) was added to a solution of commercial 2-phenoxybenzaldehyde (260 mg, 1.31 mmol) in MeOH (5 mL) at 0 C. After stirring for 30 min at 0 C, the reaction mixture was diluted with water, extracted with EtOAc, dried over MgSO4 and evaporated. The resulting residue was purified by column chromatography on silica gel (n-hexane/EtOAc = 5/1) to provide the title compound (228 mg, 1.14 mmol) in 87% yield as a colorless solid.
With hydrogenchloride; sodium borohydrid; In ethanol; ethyl acetate; (B) A mixture of 2-benzyloxybenzaldehyde (5 g, Apin) and sodium borohydride (1.4 g) in ethanol (50 ml) was stirred under argon for 1 hour. The solvent was evaporated, the residue dissolved in ethyl acetate and added dropwise to 0.1M hydrochloric acid solution (200 ml) at 0 C. The organic solution was washed with saturated aqueous sodium hydrogen carbonate (100 ml) and brine (100 ml), dried (sodium sulphate), filtered and evaporated to give 2-benzyloxybenzyl alcohol (4.91 g) as an oil.
With hydrogenchloride; sodium tetrahydroborate; In ethanol; Step L Preparation of 2-(benzyloxy)benzyl alcohol To a stirring solution of 2-(benzyloxy)benzaldehyde (10 g, 47 mmol) in 100 mL of Ethanol, NaBH4 was added as a solid in small portions. The reaction temperature was controlled with a room temperature water bath. After stirring for 30 minutes, the reaction was quenched by slow addition of 3N HCl. This solution was extracted with EtOAc and the organic portion washed with water, Sat. Na2CO3 and brine. The solution was dried (Na2SO4), filtered, and concentrated in vacuo to provide the benzy alcohol which was used in the next step without further purification.
With sodium tetrahydroborate; In methanol; at 0 - 20℃; 2-Hydroxybenzaldehyde (19.3 g) and benzyl bromide (25.9 g) were dissolved in N,N-dimethylformamide (50 mL). Cesium carbonate (59.0 g) was added to the solution at 0C, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with diethyl ether. The organic layer was washed with 1 mol/L aqueous sodium hydroxide solution, water and brine successively, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give 2-benzyloxybenzaldehyde. This compound was dissolved in methanol (100 mL). Sodium borohydride (5.73 g) was added to the solution at 0C, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and water was added to the residue. The mixture was extracted with diethyl ether, and the organic layer was washed with 1 mol/L aqueous sodium hydroxide solution, water and brine successively, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give the title compound (32.4 g).1H-NMR (CDCl3) δ ppm: 2.28 (1H, t, J=6.6Hz), 4.74 (2H, d, J=6.6Hz), 5.13 (2H, s), 6.93-7.00 (2H, m), 7.23-7.45 (7H, m)
With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 2.5h; To a solution of 2-benzyloxybenzaldehyde (2.0 g) in methanol (20 mL), NaBH4 (356 mg, 9.42 mmol) was added under ice cooling and stirred for 1 hour. After addition of additional NaBH4 (49 mg), the reaction mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated and water was added to the resulting residue, followed by extracting the mixture with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to give 2-benzyloxybenzyl alcohol (2.1 g) as a colorless oil. To a solution of 2-benzyloxybenzyl alcohol (2.1 g, 9.42 mmol) in tetrahydrofuran (10 mL), triethylamine (1.38 mL, 9.89 mmol) and methanesulfonyl chloride (0.766 mL, 9.89 mmol) were added under ice cooling and stirred at room temperature for 30 minutes. After filtration to remove the insoluble materials, the filtrate was concentrated to give (2-benzyloxyphenyl)methyl mesylate (3.24 g). To a suspension of methyl isobutyrylacetate (1.43 g, 9.89 mmol), sodium hydride (60% in oil; 396 mg, 9.89 mmol) and dimethoxyethane (10 mL), a solution of (2-benzyloxyphenyl)methyl mesylate (3.24 g) in dimethoxyethane (10 mL) was added and stirred at 70C overnight. After addition of 0.5 M HCl, the reaction mixture was extracted twice with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to give an oil. To this oil, toluene (20 mL) and hydrazine monohydrate (317 mg, 9.89 mmol) were added and the resulting mixture was heated under reflux for 3 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, washed with water and dried over anhydrous magnesium sulfate. The reaction mixture was concentrated and the resulting residue was purified by silica gel column chromatography (chloroform:methanol = 50:1 to 8:1) to give the titled compound (750 mg, 25%) as a light-yellow amorphous substance. 1H-NMR (200 MHz, CDCl3): δ 1.08 (d, J = 7.5Hz, 6H), 2.93 (quint, J = 7.5Hz, 1H), 3.75 (s, 2H), 5.12 (s, 2H), 6.82-6.95 (m, 2H), 7.09-7.19 (m, 2H), 7.31-7.50 (m, 5H). ESI m/z = 345(M+Na).
Example 37; Ethyl 3-(4-[2-(benzyloxy)benzyl]oxy}-3,5-difluorophenyl)propanoate 2-(Benzyloxy)benzaldehyde (274 mg, 1.3 mmol) dissolved in methanol (20 mL), sodium borohydride (73 mg, 1.9 mmol) was added thereto, and then the mixture was stirred with ice cooling for 2 hours. To the reaction solution was added water, and the reaction mixture was extracted with ethyl acetate. The extract was dried, and then concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (10 mL). Ethyl 3-(3,5-difluoro-4-hydroxyphenyl)propanoate (200 mg, 0.86 mmol), tributylphosphine (0.23 mL, 1.1 mmol) and azodicarbonyldipiperidine (282 mg, 1.1 mmol) were added thereto, and the mixture was stirred at room temperature for 12 hours. The reaction solution was purified with alumina column chromatography (ethyl acetate) and silica gel column chromatography (hexane/ethyl acetate = 100 : 0 to 80 : 20) to give the title compound (162 mg, yield 29%) as an oily matter.
With sodium methylate; In methanol; N,N-dimethyl-formamide; at 120℃; for 15h;Inert atmosphere; General procedure: To a solution of aldehyde/nitro compound (1 g) in dry DMF/xylene was added sodiummethoxide (10 equiv.) in methanol (5 ml). CuI (1 equiv.) was added whereverrequired. Reaction mixture was flushed by nitrogen, kept at 120oCfor appropriate time under nitrogen balloon andwater (100 ml) was added. It was extracted with ethyl acetate (3x75 ml) andcombined organic layer was dried over Na2SO4. Filtratewas concentrated under vacuum and the residue was further purified by columnchromatography in ethyl acetate/hexane as an eluent with appropriate polarityto get the product.
With sodium tetrahydroborate; In tetrahydrofuran; at 0℃; for 1h;Inert atmosphere; General procedure: Sodium borohydride (75.74 mmol) was added to a stirred solution of benzyl protected aldehyde (37.73 mmol) in 60 mL of THF at 0 oC. The reaction mixture was stirred vigorously for 1h. The reaction was quenched by dropwise addition of water at 0 oC. The aqueous layer was extracted with ethyl acetate (3 Χ 50 mL), and the organic layer was dried over anhydrous Na2SO4. After concentration under vacuum the crude product was chromatographed on silica gel (eluent =hexane/ethyl acetate, 9/1) to give 1 as colorless oil in good yield.
With methanol; sodium tetrahydroborate; for 1h;Cooling with ice; General procedure: To a solution of compound 7a (1.06 g, 10 mmol) in methanol(10 mL) was added NaBH4 (0.57 g, 15 mmol). After stirring for 1 hwhile cooled with an ice-water bath, methanol was evaporatedand the residue was dissolved in EtOAc (100 mL). The organic layerwas washed with water (3 100 mL) and brine (3 100 mL), anddried over MgSO4 overnight. EtOAc was evaporated to give 8a ascolorless oil (2.01 g, yield: 94%). ESI-MS m/z 109.4 [M+H]+. The crude product was used directly in the next reaction without furtherpurification. Compounds 8b-8u, 8aa-8ff, 10v-10w, 17a-17b and 22a-22hwere prepared using the same procedure described above

  • 3
  • [ 17672-21-8 ]
  • [ 5896-17-3 ]
  • [ 186501-24-6 ]
  • 4
  • [ 939-57-1 ]
  • [ 5896-17-3 ]
  • 3-(2’-methylphenyl)-(E)-propenoic acid benzyl ester [ No CAS ]
 

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