Structure of 38430-55-6
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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. : | 38430-55-6 |
Formula : | C11H12O3 |
M.W : | 192.21 |
SMILES Code : | O=C(OCC)C1=CC=C(C(C)=O)C=C1 |
MDL No. : | MFCD00013241 |
InChI Key : | GLOAPLPTWAXAIG-UHFFFAOYSA-N |
Pubchem ID : | 600911 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.27 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 52.72 |
TPSA ? Topological Polar Surface Area: Calculated from |
43.37 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.27 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.9 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.07 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.43 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.28 |
Solubility | 1.0 mg/ml ; 0.00523 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.43 |
Solubility | 0.708 mg/ml ; 0.00368 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.22 |
Solubility | 0.117 mg/ml ; 0.000607 mol/l |
Class? Solubility class: Log S scale |
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) |
No |
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) |
No |
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 |
-6.12 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 |
1.0 |
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 |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.37 |
* 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 |
---|---|---|
99% | With sodium tetrahydroborate; ethanol; for 2h;Reflux; | Ethyl-4-acetylbenzoate (550 mg, 2.86 mmol) was dissolved in ethanol (13 mL) and treated with sodium borohydride (10% on basic alumina, 300 mg). This suspension was heated to reflux for 2 hrs, then cooled to room temperature and filtered. The ethanol was removed by rotary evaporation; the residue was taken up in ethyl acetate and washed sequentially with IN HCl and brine, and dried over sodium sulfate. The solvent was removed under reduced pressure to yield racemic 4-(l-hydroxy-ethyl)-benzoic acid methyl ester as a colorless oil, 549 mg (99%). 1H NMR (300 MHz, CDCl3): 58.02 (d, J= 8.0 Hz, 2 H), 7.42 (d, J= 8.0 Hz, 2 H), 4.94 (q, J= 6.5 Hz, 1 H), 4.36 (q, J= 6.5 Hz, 2 H), 1.51 (d, J = 8.5 Hz, 3 H), 1.37 (t, J= 7.3 Hz, 3 H). LC-MS m/z = 195 [C10H12O3 + H]+. |
99% | With Na(1+)*C12H33AlNO4Si2(1-); In tetrahydrofuran; toluene; at 0℃; for 1h;Inert atmosphere; | General procedure: A dry and argon-flushed flask, equipped with a magnetic stirring bar and septum, was charged with 4-acetylbenzaldehyde (1.0 mmol) and THF (10 mL). After cooling to 0 C, the modified Red-Al (0.5 M, 2.2 mL in THF) was added dropwise and the mixture was stirred for 1 h at 0 C. The reaction was quenched with 1 N aqueous HCl (10 mL) and the product was extracted with diethylether (10 mL). The organic layer was dried over anhydrous magnesium sulfate, the solvent was removed under reduced pressure and the crude residue was purified by column chromatography (SiO2, ethyl acetate/hexane, 1:5 v/v) to affording the desired alcohol (123 mg, 83% yield). |
88% | With potassium diisobutyl-tert-butoxyaluminum hydride; In tetrahydrofuran; at 0℃; for 1h;Inert atmosphere; | General procedure: A dry and argon-flushed flask, equipped with a magnetic stirring bar and a septum, was charged with dicarbonyl compound (1.0 mmol) and 10 mL THF. After cooling to 0C, PDBBA (1.3 mmol) was added dropwise and stirred for 1h at same temperature. The reaction was stopped by the aqueous 1N HCl (10mL) and extracted with diethyl ether (2×10mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel afforded the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; at 80℃; under 760.051 Torr; for 6h; | General procedure: The catalytic reactions were carried out in a 10 mL reaction flask and fitted with condenser and carbon monoxide balloon. In a typical run, a catalyst containing 1.0 mol% Pd, aryl iodide (0.5 mmol) and DBU (1.5 mmol) were added to solvent and allowed to react under CO atmosphere at 80 C temperature for 6-10 h. After the reaction,the flask was cooled to room temperature and carbon monoxide balloon was removed. The reaction mixture was then centrifuged and the clear supernatant was analyzed with GC by using n-butanol as an internal standard. For the study of substrate scope, after completion of the reaction, the catalyst was centrifuged and extracted with copious ethanol. The obtained liquid was concentrated. For phenoxycarbonylation, the obtained liquid was diluted with saturated NH4Cl and extracted with diethyl ether. The organic layer was dried over anhydrous Na2SO4 and then concentrated. The product was obtained by preparative thin-layer chromatography (PTLC) using petroleum ether and ethyl acetate (30:1, v/v) as eluting solvent. The purity of products was checked by NMR and yields were based on aryl iodides. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.4% | With sulfuric acid; at 80℃; | A solution of 4-acetylbenzoic acid (13.0 g, 79.2 mmol) in ethanol(100 mL) was stirred in ice bath. Concentrated H2SO4 wasslowly added and the mixture was refluxed at 80 C for 3 h.Extracted with EtOAc, washed with saturated brine, dried overanhydrous Na2SO4 and concentrated. The residue was purified bychromatography to afford ethyl 4-acetylbenzoate as a white solid(13.6 g, 89.4%). 1H NMR (400 MHz, DMSO-d6) d 8.06 (m, 4H), 4.35(q, J = 7.1 Hz, 2H), 2.63 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H). MS (ESI, m/z): 191.1 [MH]. |
87% | With graphene oxide; at 100℃; for 24h; | General procedure: A mixture of acid (0.2 mmol), alcohol (0.6 mmol) and GO (50 wt%, calculated with the mass of acid) in ethyl alcohol or DCE (1 mL) was placed in a test tube equipped with a magnetic stirring bar. The mixture was stirred at 100 C for 24 h. After the reaction was finished, filtered the GO, solvent was removed, and the residue was separated by column chromatography to give the pure sample. |
85.4% | With sulfuric acid; at 80℃; for 3h; | A solution of 4-acetylbenzoic acid (10 g, 60.9 mmol) in ethanol (100 mL) was stirred in ice bath. After H2SO4 was slowly added, the mixture was refluxed at 80 C for 3 h. The mixture was extracted with EtOAc, washed with saturated brine, dried (Na2SO4), and concentrated. The residue was purified by chromatography to afford ethyl 4-acetylbenzoate as a white solid (10 g, 85.4%). 1H NMR (400 MHz, CDCl3) delta 8.13-8.09 (m, 2H), 7.99 (dt, J = 6.7, 1.0 Hz, 2H), 4.39 (q, J = 7.1 Hz, 2H), 2.63 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H). MS (ESI, m/z): 193.1 [M+H]+. |
With sulfuric acid; for 8h;Reflux; | General procedure: To a solution of substituted benzoic acid (1-15)(0.246 mol) in dry ethanol (2.5 mol), concentrated sulphuricacid (0.5 mL) was added. The reaction mixture was refluxedfor 8 h. Excess of ethanol was distilled off and the contentwas allowed to cool. The residue was poured into separatingfunnel containing 60 mL of water. Carbon-tetrachloride(5-10 mL) was added to obtain sharp separation of aqueousand ester layer. Ester layer was washed with sodiumhydrogen carbonate solution. The esters (16-30) were collected and recrystallized from ethanol. Details of thesecompounds are available in Supplementary Information. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With hydrogen;trans-RuH(eta1-BH4)[(S)-xylbinap][(S,S)-dpen]; In isopropyl alcohol; at 25℃; under 6080.41 Torr; for 15h;Conversion of starting material; | Chiral hydrogenation of ethyl 4-acetylbenzoate was carried out (see formula (9) below). That is, a reaction was carried out in accordance with the procedures of Example 4 using the (S,SS)-ruthenium hydride complex (1.5 mg; 0.00125 mmol) synthesized in Example 2 and using ethyl 4-acetylbenzoate (961 mg; 5.00 mmol) (Wako.Co.,Ltd.) as the substrate and 2-propanol (5 mL) as the solvent. However, the hydrogen pressure was set to 8 atmosphere, the reaction temperature was set to 25 C., and the reaction time was set to 15 hours. As a result, ethyl (R)-4-(1-hydroxyethyl) benzoate was obtained at a conversion rate of 100%, isolation yield of 98% (951 mg; 4.9 mmol), and enantiomeric excess of 99%. GC (column: Chirasil-DEXCB; column temperature: 150 C.; injection and detection temperature: 250 C.; helium pressure: 49 kPa; tR of ethyl (R)-4-(1-hydroxyethyl) benzoate : 32.2 minutes (99.4%); tR of ethyl (S)-4-(1-hydroxyethyl) benzoate: 35.1 minutes (0.6%)); tR of ethyl 4-acetylbenzoate 35.5 minutes (0%); [alpha]26D: +32.0 (c:0.912; CH3OH); absolute structure: R; literature value: [alpha]21D+32.6 (c:0.873; CH3OH), 98.6% ee (R). |
77.2% | With dimethylsulfide borane complex; (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole; In dichloromethane; toluene; at -20℃; for 1.16667h; | To a dry 100 mL three neck flask at room temperature was added dichloromethane (15 mL)A solution of borane dimethyl sulfide (0.7 mL, 7.0 mmol) and (S) -Me-CBS (1 M solution in toluene, 5.7 mL, 6.0 mmol) was directly added and stirred for 60 minutes. At -20 C, a solution of ethyl 4-acetophenone acetate (1.0 g, 5.4 mmol) in methylene chloride (10 mL) was added dropwise over a period of about 10 minutes using a constant-pressure funnel.And an internal temperature of -20 C ± 5 C. The reaction was continued for 1 hour at the same temperature. The reaction was quenched by slow addition of methanol (5 mL), keeping the internal temperature below -20 C ± 5 C. The organic phase was poured off and the organic phase was washed with saturated sodium chloride (30 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo. Washed once. The organic layer was dried over anhydrous sodium sulfate, and the organic layer was concentrated to a solvent-free residue. The resulting product was separated by chromatography (petroleum ether / ethyl acetate = 1/4) to give the final product (R) -1-hydroxyethyl- -benzoic acid ethyl ester (780 mg, 77.2%). |