Structure of 60186-33-6
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
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 |
35.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.72 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.12 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.32 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.49 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.97 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.13 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.47 |
Solubility | 0.0876 mg/ml ; 0.000342 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.53 |
Solubility | 0.0748 mg/ml ; 0.000292 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.54 |
Solubility | 0.000731 mg/ml ; 0.00000285 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
Yes |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.65 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.06 |
* 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.
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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) |
Yield | Reaction Conditions | Operation 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) |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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) |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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) |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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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