Structure of 2107-69-9
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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. : | 2107-69-9 |
Formula : | C11H12O3 |
M.W : | 192.21 |
SMILES Code : | C1=C2C(=CC(=C1OC)OC)C(CC2)=O |
MDL No. : | MFCD00003790 |
InChI Key : | IHMQOBPGHZFGLC-UHFFFAOYSA-N |
Pubchem ID : | 75018 |
GHS Pictogram: |
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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 | 0.36 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 52.47 |
TPSA ? Topological Polar Surface Area: Calculated from |
35.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.21 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.61 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.83 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.03 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.73 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.88 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.23 |
Solubility | 1.13 mg/ml ; 0.00587 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.97 |
Solubility | 2.07 mg/ml ; 0.0108 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.37 |
Solubility | 0.0812 mg/ml ; 0.000423 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 |
-6.33 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) |
1.84 |
* 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 |
---|---|---|
98% | With potassium hydroxide; In water; at 25 - 30℃; for 3h;Product distribution / selectivity; | Example 1: Process for preparation of 5,6-dimethoxy-2-(4-pyridylmethylene)-l- indanone of formula IVTo a 1 liter round bottom flask equipped with a mechanical stirrer, thermometer pocket, addition funnel and a condenser, charged demineralized water (250ml), 5,6- dimethoxy-l-indanone (25g) and pyridine-4-carboxaldehyde (19.5g). The reaction mixture was stirred for 5 minutes at a temperature of 25C to 30C. To the reaction mixture then charged a solution of potassium hydroxide (5.2g) dissolved in demineralized water (125ml) slowly over period of 2 hours at a temperature of 25 C to 30C. The reaction mixture was further maintained at a temperature of 25C to 30C for 1 hour to obtain the product, 5,6-dimethoxy-2-(4-pyridylmethylene)-l- indanone. The product obtained was then filtered and washed with demineralized water. Dry the product under vacuum at a temperature of 50C to 55C for 10 hours. Yield: 98%Purity: 99.71% |
95.8% | 5, 6 Dimethoxy indanone (100 grams), Pyridine-4-carboxaldehyde (78.0 grams) and p-toluene sulfonic acid (138.4 grams) were suspended in toluene (1250 ml) and heated to reflux using water separator for 6 hours. The resulting mass was cooled to 25-40 C. and the solid was filtered off under suction. Further the wet solid was suspended in aqueous 10% sodium carbonate solution (1200 ml) and stirred for 30-60 minutes. The resulting pale yellow precipitate solid was filtered off under suction, washed with water (1000 ml) and dried at a temperature of 80 C. to afford 5,6 Dimethoxy-2-(pyridin-4yl)-methylene-indan-lone (Weight: 140 grams, 95.8%). | |
92.2% | With potassium iodide; calcium chloride; In acetone; at 40 - 50℃; for 4h; | In a three-necked flask equipped with a condenser and a stirrer, acetone 60 mL, 5,6-dimethoxy-1-indanone was sequentially added.9.6g, anhydrous calcium chloride 5.55g (0.05mol), 4-pyridine formaldehyde 5.89g, potassium iodide 0.96g, stirred at 40 ~ 50 CAfter mixing for 4 h, the basic reaction was completely monitored by HPLC, cooled to room temperature, filtered, and the filtrate was concentrated.Filtration and drying under vacuum gave Compound III 12.96 g, yield 92.2%, HPLC, purity 99.7%. |
67% | With sodium hydroxide; In ethanol; water; at 20℃;Inert atmosphere; | To a solution of 1 mmol of 4-pyridinecarboxaldehyde and 1 mmol of 5,6-dimethoxy-1-indanone in 10 ml EtOH, aqueous solution of NaOH (10%) was added dropwise. The reaction mixture was stirred overnight at room temperature. The obtained solid was fltered and recrystallized from EtOH to give 3 as an of-white solid [22]; yield 67%; mp: 118-120 C; FTIR (KBr) nu3008, 2937, 1691, 1600, 1465, 1315, 1268, 1029 cm-1; 1H NMR (400 MHz, CDCl3): 3.82 (3H, s, OCH3), 3.91 (3H, s, OCH3), 4.03 (2H, s, CH2), 7.17 (1H, s, Ar), 7.22 (1H, s, Ar), 7.42 (1H, s, =CH), 7.67 (2H, d, 3JH-H = 5.36, pyridine-H), 8.64 (2H, d, 3JH-H = 5.46, pyridine-H). |
With toluene-4-sulfonic acid; In toluene; for 6h;Heating / reflux; | Preparation 1 Preparation of 5, 6-dimethoxy-2- (pyridine-4-yl) methylene-indan-1-one A mixture OF 5, 6-DIMETHOXY-INDAN-1-ONE (100G), pyridine-4-carboxaldehyde (67g), p- toluene sulfonic acid (118G) in toluene (1200ML) was refluxed azeotropically for 6 hours. The reaction mixture was cooled to room temperature and filtered. The wet solid so obtained was stirred with 10% aqueous sodium carbonate solution. The solid was filtered, washed with acetone and then dried to get the title compound (130G). HPLC Purity: 99.5% | |
With sodium hydroxide; In methanol; at 20℃; for 4h; | General procedure: 5,6-dimethoxy-2,3-dihydro-1H-inden-1-one (0.001 mol) with appropriate aldehyde (0.001 mol) in diluted methanolic sodium hydroxide solution was stirred under room temperature for 4 h. The resulting solution was allowed to stand overnight and then the reaction mixture was poured into cold water and neutralized with dilute HCl. The solid was filtered, dried and recrystallized with ethanol furnished the 2-substituted-5,6-dimethoxy-2,3-dihydro-1H-indene-1-one. |
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