Structure of 63697-96-1
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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. : | 63697-96-1 |
Formula : | C9H6O |
M.W : | 130.14 |
SMILES Code : | O=CC1=CC=C(C#C)C=C1 |
MDL No. : | MFCD05664348 |
InChI Key : | BGMHQBQFJYJLBP-UHFFFAOYSA-N |
Pubchem ID : | 2771645 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 39.76 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.76 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.63 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.56 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.01 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.62 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.92 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.05 |
Solubility | 1.16 mg/ml ; 0.00888 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.6 |
Solubility | 3.26 mg/ml ; 0.0251 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.39 |
Solubility | 0.529 mg/ml ; 0.00406 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 |
-5.94 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 |
2.0 |
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 |
2.0 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) |
1.45 |
* 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 hydrogen; triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In acetonitrile; at 20 - 75℃;Inert atmosphere;Product distribution / selectivity; | Method 4; 4-(4-((4-(5,5-dimethyl-l,3,2-dioxaborinan-2-yl)phenyl)ethynyl)benzyl) morpholine; A. 4-((4-(5,5-dimethyl-l,3,2-dioxaborinan-2-yl)phenyl)ethynyl)benzaldehyde; 4-((4-(5,5-Dimethyl-l,3,2-dioxaborinan-2-yl)phenyl)ethynyl)benzaldehyde was prepared following the method described in Method 3 steps A-C to yield 50.O g (99% yield) of the title compound as a yellow solid. LC-MS: [M+H]+ 319.0 1H NMR (400 MHz, CDCl3) δ: ppm 10.02 (s, IH), 7.95 (d, 2H), 7.79 (m, 4H), 7.66 (d, 2H), 3.78 (s, 4H), 1.00 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; at 60℃; for 0.5h; | General procedure: A mixture of corresponding hydrazinylpyridazine 1 or 5 (1 mmol) and aldehyde 2 (1.1 mmol) in ethanol (5 mL) was heated at 60 oC for 0.5 h. The formation of hydrazone was checked by TLC and the reaction mixture was cooled to rt. Oxone (1.5 mmol) was added to the mixture at rt followed by tetramethyl ammonium bromide (0.2 mmol) and the resulting mixture was heated at 60 oC for another 5 h. The mixture was cooled to rt and extracted with dichloromethane (2 × 25 mL), dried over anhydrous sodium sulphate and concentrated to obtain a residue which was purified by column chromatography using hexane/ethyl acetate as eluent to furnish the desired triazolopyridazines 4 and 7. | |
In ethanol; at 60℃; for 0.5h; | General procedure: A mixture of corresponding hydrazinylpyridazine 1 or 5 (1 mmol) and aldehyde 2 (1.1 mmol) in ethanol (5 mL) was heated at 60 C for 0.5 h. The formation of hydrazone was checked by TLC and the reaction mixture was cooled to rt. Oxone (1.5 mmol) was added to the mixture at rt followed by tetramethyl ammonium bromide (0.2 mmol) and the resulting mixture was heated at 60 C for another 5 h. The mixture was cooled to rt and extracted with dichloromethane (2 × 25 mL), dried over anhydrous sodium sulfate and concentrated to obtain a residue which was purified by column chromatography using hexane/ethyl acetate as eluent to furnish the desired triazolopyridazines 4 and 7 (See reference no; 7 for supporting information). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | General procedure: General synthetic procedure for 3a/3b/3c: 6-Bromocoumarin(0.5 g, 2.23 mmol), (4-ethynyl)benzaldehyde (0.29 g, 2.23 mmol)were dissolved in THF-triethylamine (1:1, v/v, 120 mL) and themixture was deaerated for 10 min with nitrogen bubbling and thenPd(PPh3)2Cl2 (31 mg, 2mol%), PPh3 (23 mg, 4 mol%)and CuI (8 mg,2mol%) were added. The solution was deaerated for an additional5 min; after that, reaction was left under nitrogen at 60C for 12 h.After completion of the reaction, the reaction mixture was cooledat room temperature and the solvent was evaporated. The crudeproduct was dissolved in CH2Cl2 and purified by a columnchromatography on a silica gel using (chloroform) as an eluent.Synthesis of 3a. Yield, 61% (0.37 g), 1H NMR (600 MHz, CDCl3) d10.04 (s, 1H,CHO), 7.89 (d, J = 8.25, 2H, aromatic), 7.70-7.68 (m,5H, aromatic), 7.35 (d, J = 9.17, 1H, aromatic), 6.48 (d, J = 9.55, 1H,aromatic).13C (150 MHz, CDCl3) d 192.67, 159.58, 153.76, 143.58,135.70, 134.89, 132.15, 131.81, 129.82, 127.88, 119.28, 117.80, 117.35,117.30, 91.58, 88.79. MS (m/z) 275 (M + H). | |
58% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In tetrahydrofuran; for 8h;Reflux; Inert atmosphere; | General procedure: The resulting bromocoumarin was reacted with 4-ethynylbenzaldehyde in the presence of Pd (PPh3) 2Cl2 and CuI in THF / triethylamine (1: 1 v / v)Was refluxed in N2 atmosphere (atm) for 8 hours,Ethynyl) benzaldehyde [4 - ((2-oxo-2H-chromen-6-yl) ethynyl) benzaldehyde] Ethynyl) benzaldehyde, 4 - ((2-oxo-2H-chromen-7-yl) ethynyl) benzaldehyde,(3a, 3b, 3c) was reacted with 4 - ((2-oxo-2H-chromen-8- yl) ethynyl) benzaldehyde Respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | General procedure: General synthetic procedure for 3a/3b/3c: 6-Bromocoumarin(0.5 g, 2.23 mmol), (4-ethynyl)benzaldehyde (0.29 g, 2.23 mmol)were dissolved in THF-triethylamine (1:1, v/v, 120 mL) and themixture was deaerated for 10 min with nitrogen bubbling and thenPd(PPh3)2Cl2 (31 mg, 2mol%), PPh3 (23 mg, 4 mol%)and CuI (8 mg,2mol%) were added. The solution was deaerated for an additional5 min; after that, reaction was left under nitrogen at 60C for 12 h.After completion of the reaction, the reaction mixture was cooledat room temperature and the solvent was evaporated. The crudeproduct was dissolved in CH2Cl2 and purified by a columnchromatography on a silica gel using (chloroform) as an eluent. |
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