Structure of 15174-69-3
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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. : | 15174-69-3 |
Formula : | C8H8O2 |
M.W : | 136.15 |
SMILES Code : | C1=C(C(=CC=C1C=O)O)C |
MDL No. : | MFCD00012360 |
InChI Key : | BAKYASSDAXQKKY-UHFFFAOYSA-N |
Pubchem ID : | 139901 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 38.82 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.36 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.73 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.51 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.12 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.96 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.34 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.52 |
Solubility | 4.09 mg/ml ; 0.0301 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.09 |
Solubility | 11.0 mg/ml ; 0.0809 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.13 |
Solubility | 1.02 mg/ml ; 0.00746 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) |
No |
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 |
-6.61 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 |
1.0 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) |
1.0 |
* 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 |
---|---|---|
To a solution [OF 4-HYDROXY-3-METHYLBENZALDEHYDE (10G,] 73.5 [MMOL)] in dry [CH2CI2] (550 mL) under nitrogen at [5C] was added tetra-N-butylammonium borohydride (20.58 g, 80 [MMOL)] and the resultant mixture stirred for 1.25 h at [5C.] Saturated ammonium chloride solution (30 mL) was added to the reaction mixture and the resultant mixture stirred for 1 h at [5C.] Saturated ammonium chloride solution (60 mL) was added and the reaction mixture extracted with [CH2CI2,] dried [(NA2SO4)] and the solvents removed in vacuo. Purification by flushing through silica (2 x 150 g) eluting with EtOAc afforded the title compound as an oily yellow solid (8.01 g). [1H] NMR (400 MHz; [MEOH-D4)] 8 : 2.19 (3H, s), 4.46 (2H, s), 6.71 [(1H, D,] J 8Hz), 6.99 [(1H,] dd, J 8Hz, 2Hz), 7.06 (1 H, d, J 2Hz), OH not observed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With hydroxylamine hydrochloride; acetic acid; for 1.5h;Heating / reflux; | Preparation 70: 4-Hydroxy-3-methylbenzonitrile A mixture of 4-hydroxy-3-methylbenzaldehyde (530 mg, 3.91 mmol) and hydroxyl ammonium chloride (406 mg, 5.81 mmol) in acetic acid (5 mL) was heated under reflux for 90 minutes. The cooled reaction mixture was then diluted with diethyl ether (30 mL) and washed with water (30 mL). The combined organic solution was washed with brine, dried over magnesium sulfate, concentrated in vacuo and the residue was purified by column chromatography on silica gel, eluting with dichloromethane:methanol, 100:0 to 97.5:2.5, to afford the title compound as a pale yellow oil in 66% yield, 345 mg. 1H NMR(400 MHz, CDCl3) δ: 2.25(s, 3H), 6.84(d, 1H), 7.37(d, 1H), 7.40(s, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[00607] To a mixture of <strong>[34956-31-5]N-(4-acetyl-3-methylphenyl)acetamide</strong> (1.3g, 7.0 mmol) and NaOH (1.4 g, 36 mmol) in 25 mL of absolute EtOH was added 4-hydroxy-3-methylbenzaldehyde (1.0 g, 7.3 mmol). The reaction mixture was stirred at room temperature for 18 hr. 5 mL of water was added and the reaction mixture was acidified with concentrated HCl to pH 5-6. The aqueous layer was extracted with two 25 mL portions of EOAc, and the layers were separated. The organic layer was dried with Na2SO4, filtered and concentrated under reduced pressure. The resulting product was submitted to the next step without further purification. MS (EI) for Ci9Hi9NO3: 310 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | [00248] To a round bottomed flask was added EtOH (30 mL) and potassium hydroxide (6.0 g, 109.5 mmol). The mixture was stirred until homogeneous before adding commercially available 4-hydroxy-3-methyl benzaldehyde (3.Og, 21.9 mmol) and commercially available 4- acetamido-2-methyl acetophenone (4.2 g, 21.9 mmol). The reaction was heated to 80 0C overnight, cooled to rt, and concentrated via rotary evaporation. The solid was dissolved in H2O and neutralized with IN HCl until pH =7. The aqueous mixture was extracted 5 X with EtOAc. The combined EtOAc layers were concentrated and column purified on silica gel (1 : 1 EtOAc: Hexanes) to afford (E)-I -(4-amino-2-methylphenyl)-3-(4-hydroxy-3-methylphenyl) prop-2-en-l -one (2) (3.1 g, 55% yield).1H NMR (400 MHz, d6-DMSO) δ 7.64 (dd, 2H), 7.37 (s, 2H), 6.81 (d, IH), 6.42 (m, 2H), 5.87 (d, 2H), 2.38 (d, 4H), 2.15 (s, 2H); MS (EI) for Ci7H17NO2: 268.2 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
00267) To a mixture of commercially available 4'-hydroxy-3'-methylacetophenone (700 mg, 4.66 mmol) and NaOH (365 mg, 9.1 mmol) in 10 mL of absolute EtOH was added commercially available 5-methylisoxazole-3-carbaldehyde (518 mg, 4.66 mmol). The reaction mixture was stirred at room temperature for 18 hr. 5 mL of water was added and the reaction mixture was acidified with concentrated HCI to pH 5-6. The precipitate was filtered, washed15 <n="117"/>with water and dried to give (E)-l-(4-hydroxy-3-methylphenyl)-3-(5-methylisoxazol-3- yl)prop-2-en-l-one. MS (EI) for Ci4H13NO3: 244 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With acetic acid; In ethanol; at 80℃; for 0.166667h;Microwave irradiation; | General procedure: A mixture of compound 2 (0.0549 g, 0.0003 mol), the appropriate aromatic aldehyde (0.00033 mol) and glacial acetic acid (0.1 mL) in ethanol (5 mL) was heated under microwave (20 W) at 80 °C for 10 min. On cooling, the precipitated solid was collected by filtration, washed with water, dried and crystallized to give compounds 3-29. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tris(acetoxy)borohydride; N-ethyl-N,N-diisopropylamine; In 1,2-dichloro-ethane; at 20℃; | To a solution of 4-hydroxy-3-methylbenzaldehyde (Aldrich cat316911: 400.0 mg, 2.938 mmol) and N,N-diisopropylethylamine (8.8 mmol) in 1,2-dichloroethane (200 mmol) was added <strong>[18650-39-0](S)-methyl piperidine-2-carboxylate hydrochloride</strong> (Combi-Blocks catSS-2950: 690 mg, 3.8 mmol) followed by sodium triacetoxyborohydride (1.9 g, 8.8 mmol). The mixture was stirred at room temperature overnight. The crude reaction mixture was diluted with DCM, then sequentially washed with an aqueous NaHCO3 solution, water, and brine. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography eluting with 40percent ethyl acetate in hexanes to give the desired product. LC-MS calculated for C15H22NO3 (M+H)+: m/z=264.2; found: 264.2. |
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