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Structure of 60186-33-6

Chemical Structure| 60186-33-6

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Product Details of [ 60186-33-6 ]

CAS No. :60186-33-6
Formula : C16H16O3
M.W : 256.30
SMILES Code : CCOC1=C(OCC2=CC=CC=C2)C=CC(C=O)=C1
MDL No. :MFCD00615145
InChI Key :NCOFQZRLIYPMNJ-UHFFFAOYSA-N
Pubchem ID :561364

Safety of [ 60186-33-6 ]

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

Computational Chemistry of [ 60186-33-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 12
Fraction Csp3 0.19
Num. rotatable bonds 6
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 74.11
TPSA ?

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

35.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.72
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

3.12
Log Po/w (WLOGP)?

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

3.32
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.

2.49
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

3.97
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.13

Water Solubility

Log S (ESOL):?

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

-3.47
Solubility 0.0876 mg/ml ; 0.000342 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.

-3.53
Solubility 0.0748 mg/ml ; 0.000292 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

-5.54
Solubility 0.000731 mg/ml ; 0.00000285 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.

-5.65 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<0.0
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)

2.06

Application In Synthesis of [ 60186-33-6 ]

* 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 [ 60186-33-6 ]

[ 60186-33-6 ] Synthesis Path-Downstream   1~22

  • 1
  • [ 60186-33-6 ]
  • [ 52009-57-1 ]
  • 2
  • [ 121-32-4 ]
  • [ 100-44-7 ]
  • [ 60186-33-6 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In water; N,N-dimethyl-formamide; at 20 - 60℃; for 3.5h; To the solution of 3-ethoxy-4-hydroxy-benzaldehyde (83g) in N,N-dimethylformamide (400ml) was gradually added 10 M sodium hydroxide (55 ml) and then benzyl chloride (60ml) was added at a temperature under 40C. The mixture was stirred at room EPO <DP n="30"/>temperature for a half an hour and for 2 hours at 6O0C. The solution was poured into ice- cold water (2 1) and extracted with diethyl ether. The organic phase was washed with water and 5M sodium hydroxide and then it was dried and evaporated. The product was recrystallized from toluene-heptane. 1H NMR (DMSOd6): delta = 1.34 (t, 3H), 4.12 (q, 2H), 5.24 (s, 2H), 7.26 (d, IH), 7.34-7.53 (m, 7H), 9.83 (s, IH).
  • 3
  • [ 7647-01-0 ]
  • [ 60186-33-6 ]
  • [ 121-32-4 ]
  • 4
  • [ 75-03-6 ]
  • protocatechualdehyde-4-benzyl ether [ No CAS ]
  • [ 60186-33-6 ]
  • 5
  • [ 14171-89-2 ]
  • [ 60186-33-6 ]
  • (E)-1-(4-Benzyloxy-3-ethoxy-phenyl)-7-phenyl-hept-1-en-3-one [ No CAS ]
  • 6
  • [ 88333-03-3 ]
  • [ 60186-33-6 ]
  • [ 2498-50-2 ]
  • (R,S)-N-benzyl-2-(4-benzyloxy-3-ethoxyphenyl)-2-(4-carbamimidoylphenylamino)acetamide [ No CAS ]
  • 7
  • [ 67-56-1 ]
  • [ 88333-03-3 ]
  • [ 60186-33-6 ]
  • [ 873-74-5 ]
  • <i>N</i>-benzyl-2-(4-benzyloxy-3-ethoxy-phenyl)-2-(4-cyano-phenylamino)-acetimidic acid methyl ester [ No CAS ]
  • 8
  • [ 4542-47-6 ]
  • [ 60186-33-6 ]
  • C23H26N2O3 [ No CAS ]
  • 9
  • [ 60186-33-6 ]
  • [ 98612-08-9 ]
  • 10
  • [ 60186-33-6 ]
  • [ 871345-40-3 ]
  • 11
  • [ 60186-33-6 ]
  • [ 937018-41-2 ]
  • 12
  • [ 60186-33-6 ]
  • (4-benzyloxy-3-ethoxy-phenyl)-(4-carbamimidoyl-phenylamino)-acetic acid [ No CAS ]
  • 13
  • [ 60186-33-6 ]
  • [ 871345-42-5 ]
  • 14
  • [ 121-32-4 ]
  • [ 100-39-0 ]
  • [ 60186-33-6 ]
YieldReaction ConditionsOperation in experiment
85% With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 40℃; for 2h; To a solution of3-ethoxy-4-hydroxy-benzaldehyde (830 mg, 5 mmol) in N'N-dimethylforrnemide (5 mL)was gradually added K2CO3 (20 mg) and then PmBr (6 mmol) was added ata temperature under 40 C. The mixture was stirred at room temperature for 2 h.The solution was poured into ice-cold water (10 mL) and extracted with diethylether. The organic phase was washed with water and sodium hydroxide and then itwas dried and evaporated to obtain 18 (1.1g, 85%). Compound 18 was reacted with sophoridine using same proceduredescribed in synthesis of 11-16 to obtain 14-(4-(benzyloxy)-3-ethoxyphenylmethylene)sophoridine (20) (120 mg, 30%)
With potassium carbonate; In acetonitrile; for 3h;Heating / reflux; 25 g of 3-ethoxy-4-hydroxybenzaldehyde, 27 g of benzyl bromide, 25 g of potassium carbonate and 250 ml of acetonitrile were mixed, and stirred under condition of reflux for 3 hours. Then the reaction mixture was cooled to room temperature. Ethyl acetate was added to it, and solid was filtered off. The obtained organic layer was concentrated under reduced pressure, the residue was washed bymethyl=tert-butylether and hexane to obtain 36 g of 4-benzyloxy-3-ethoxybenzaldehyde.1H-NMR (CDCl3, TMS) delta (ppm): 9.82 (1H, s), 7.28-7.44 (7H, m), 6.98 (1H, d, J=8.2 Hz), 5.24 (2H, s), 4.18 (2H, q, J=7.0 Hz), 1.49 (3H, t, J=7.0 Hz)
With potassium carbonate; In acetonitrile; for 3h;Heating / reflux; Reference Example 5 25 g of 3-ethoxy-4-hydroxybenzaldehyde, 27 g of benzyl bromide, 25 g of potassium carbonate and 250 ml of acetonitrile were mixed and stirred under reflux for 3 hours. After the reaction mixture was allowed to cool to room temperature, ethyl acetate was added and the mixture was filtered. The resulting filtrate was concentrated under reduced pressure. The residue was washed with tert-butyl methyl ether and hexane to obtain 36 g of 4-benzyloxy-3-ethoxybenzaldehyde. 1H-NMR (CDCl3, TMS) delta (ppm): 9.82 (1H, s), 7.28-7.44 (7H, m), 6.98 (1H, d, J = 8.2 Hz), 5.24 (2H, s), 4.18 (2H, q, J = 7.0 Hz), 1.49 (3H, t, J = 7.0 Hz)
  • 15
  • [ 6272-26-0 ]
  • [ 60186-33-6 ]
  • 2-[(3-ethoxy-4-benzyloxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In methanol; EXAMPLE 17 Synthesis of 2-[(3-ethoxy-4-benzyloxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone After 6-hydroxy-2H-benzofuran-3-one 1 g and <strong>[60186-33-6]3-ethoxy-4-benzyloxybenzaldehyde</strong> 1.80 g were dissolved in methanol 75 ml, concentrated hydrochloric acid 50 ml was added, and the mixture was refluxed for 1.5 hours. The solution was cooled to room temperature, and precipitated crystals were filtered and dried over phosphorous pentoxide at a temperature of 60 C. for four hours under reduced pressure to obtain the desired compound 1.33 g. FAB MASS; 389 (M+1) 1H-NMR (ppm, in DMSO-d6); 1.34 (3H, t), 4.08 (3H, s), 5.14 (2H, s), 6.70-6.73 (3H, m), 6.79 (1H, s), 7.08 (1H, d, J=8.5 Hz), 7.39-7.60 (8H, m), 11.11 (1H, s)
  • 16
  • [ 60186-33-6 ]
  • (RS)-N-benzyl-2-(4-benzyloxy-3-ethoxyphenyl)-2-(4-cyano-3-hydroxyphenylamino)-acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
76.2 By the method of Example 59.1, the nitrile from Example 76.1, <strong>[60186-33-6]4-benzyloxy-3-ethoxybenzaldehyde</strong> and benzylisonitrile gave (RS)-N-benzyl-2-(4-benzyloxy-3-ethoxyphenyl)-2-(4-cyano-3-hydroxyphenylamino)-acetamide.
  • 17
  • [ 60186-33-6 ]
  • [ 55149-80-9 ]
YieldReaction ConditionsOperation in experiment
With nitric acid; In dichloromethane; at 20 - 30℃; for 0.166667h; 4-Benzyloxy-3-ethoxy-benzaldehyde (2Og) was dissolved in dichloromethane (100ml) and a solution of nitric acid in dichloromethane (2M, 200ml) was gradually added at a temperature under 300C. The solution was stirred at room temperature for 10 min and then it was poured into ice-cold water. The organic phase was washed with IM sodium hydroxide and water and then it was dried and evaporated.1H NMR (DMSO-d6): delta = 1.37 (t, 3H), 4.25 (q, 2H), 5.34 (s, 2H), 7.36-7.49 (m, 5H), 7.82 (s, IH), 10.19 (s, IH)
  • 18
  • [ 109-04-6 ]
  • [ 60186-33-6 ]
  • ammonium chloride [ No CAS ]
  • [4-(benzyloxy)-3-ethoxyphenyl](pyridine-2-yl)methanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% With n-butyllithium; In tetrahydrofuran; hexane; Reference Example 217 To a solution (200 ml) of 2-bromopyridine (4.4 ml) in tetrahydrofuran was added dropwise a 1.6M solution (33 ml) of n-butyllithium in hexane at -78C, and the mixture was stirred for 30 min. To this reaction mixture was added a solution (50 ml) of <strong>[60186-33-6]4-(benzyloxy)-3-ethoxybenzaldehyde</strong> (9.1 g) in tetrahydrofuran, and the mixture was stirred at room temperature for 2 hr. Saturated aqueous ammonium chloride was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was recrystallized from ethyl acetate-hexane to give [4-(benzyloxy)-3-ethoxyphenyl](pyridin-2-yl)methanol as pale-yellow prism crystals (8.6 g, yield 68%). melting point 109 - 110C.
  • 19
  • [ 867-13-0 ]
  • [ 60186-33-6 ]
  • [ 186895-22-7 ]
YieldReaction ConditionsOperation in experiment
19 g of ethyl diethylphosphonoacetate and 400 ml of tetrahydrofuranweremixed, added 3.3 g of sodium hydride (content 60 %) under ice cooling, and stirred for 10 minutes. Then the mixture of 20 g of <strong>[60186-33-6]4-benzyloxy-3-ethoxybenzaldehyde</strong> and 50 ml of tetrahydrofuran was added gradually to it under ice cooling, and stirred at room temperature for 1 hour. Water was added to the obtained mixture. Organic solvent was distilled off under reduced pressure, and then extracted with ethyl acetate. The oil layer was separated. It was washed with water, buffer solution of PH 6.8 and saturated aqueous solution of sodium chloride, dried by magnesium sulfate, concentrated under reduced pressure. The obtained residue was washed by hexane to obtain 25 g of ethyl 3-{3-ethoxy-4-(benzyloxy)phenyl}acrylate. [] 1H-NMR (CDCl3, TMS) delta (ppm): 7.59 (1H, d, J=16 Hz), 7.28-7.44 (5H, m), 7.07 (1H, d, J=2.0 Hz), 7.02 (1H, dd, J=8.3 Hz, 2.0 Hz), 6.86 (1H, d, J=8.3 Hz), 6.28 (1H, d, J=16 Hz), 5.18 (2H, s), 4.28 (2H, q, J=7.1 Hz), 4.31 (2H, q, J=6.8 Hz), 1.47 (3H, t, J=6.8 Hz), 1.33 (3H, t, J=7.1 Hz)
Reference Example 6 19 g of ethyl diethylphosphonoacetate and 400 ml of tetrahydrofuran were mixed, and thereto 3.3 g of sodium hydride (content 60%) was added under ice-cooling. The mixture was stirred for 10 minutes. Thereto a mixture of 20 g of <strong>[60186-33-6]4-benzyloxy-3-ethoxybenzaldehyde</strong> and 50 ml of tetrahydrofuran was gradually added under ice-cooling and then stirred at room temperature for hour. After water was added, the resulting mixture was concentrated under reduced pressure and then extracted with ethyl acetate. The resulting organic layer was washed successively with water, a pH 6.8 buffer and an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was washed with hexane to obtain 25 g of ethyl 3-{3-ethoxy-4-(benzyloxy)phenyl}acrylate. 1H-NMR (CDCl3, TMS) delta (ppm): 7.59 (1H, d, J = 16 Hz), 7.28-7.44 4 (5H, m), 7. 07 (1H, d, J = 2.0 Hz), 7.02 (1 H, dd, J = 8.3 Hz, 2.0 Hz), 6.86 (1H, d, J = 8.3 Hz), 6.28 (1H, d, J = 16 Hz), 5.18 (2H, s), 4.28 (2H, q, J = 7.1 Hz), 4.31 (2H, q, J = 6.8 Hz), 1.47 (3H, t, J = 6.8 Hz), 1.33 (3H, t, J = 7.1 Hz)
  • 20
  • [ 109-04-6 ]
  • [ 60186-33-6 ]
  • [4-(benzyloxy)-3-ethoxyphenyl](pyridine-2-yl)methanol [ No CAS ]
  • 21
  • [ 1273-94-5 ]
  • [ 60186-33-6 ]
  • C46H42FeO6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With sodium hydroxide; In ethanol; at 20 - 23℃; for 24h; General procedure: A mixture of 0.033 mol of 1,1'-diacetylferrocene I, 0.01 mol of benzaldehyde or substituted alkoxybenzaldehyde II, and 0.005 mol of NaOH in 50 mL of 96% ethanol was stirred at 20-23C during 24 h. The reaction mixture was diluted with 150 mL of water, and the precipitate was filtered off, washed with large amount of distilled water (1.5-2 L), and dried at 35-40C in air. Compounds III-XXXV were purified via low-temperature recrystallization from 80% ethanol.
  • 22
  • [ 60186-33-6 ]
  • [ 6882-68-4 ]
  • 14-(4-(benzyloxy)-3-ethoxyphenylmethylene)sophoridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
30% With sodium hydride; In tetrahydrofuran; mineral oil; at 37℃; for 13h;Reflux; General procedure: Sophoridine(200 mg, 0.8 mmol) and 60% sodium hydride (806 mg, 20 mmol) into around-bottomed flask (50 mL) were resolved in anhydrous tetrahydrofuran (20mL). The solution was stirred and aldehyde (4 mmol) was added at 37 C andstirred for 1 h. The solution was then refluxed for 12 h. After cooling to roomtemperature, the mixture was pouredinto water (10 mL), acidified to pH=1~3 with 2N HCl and extracted with dichloromethane(3 × 40 mL). The aqueous phase was adjusted to pH=10~11 with 2N NaOH, and extracted with dichloromethane (3 × 40mL). The solvent was removed in vacuo, and the residue was purified by flashsilica gel column chromatography (petroleum ether/acetone, 10%) to afford 11-16.
 

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