Structure of 18048-64-1
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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. : | 18048-64-1 |
Formula : | C12H14N2O |
M.W : | 202.25 |
SMILES Code : | O=C1CC(C)=NN1C2=CC=C(C)C(C)=C2 |
MDL No. : | MFCD00638319 |
InChI Key : | GJBBAPXESBCGRU-UHFFFAOYSA-N |
Pubchem ID : | 3714577 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 68.23 |
TPSA ? Topological Polar Surface Area: Calculated from |
32.67 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.49 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.0 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.65 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.17 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.13 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.29 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.58 |
Solubility | 0.527 mg/ml ; 0.00261 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.31 |
Solubility | 0.985 mg/ml ; 0.00487 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.65 |
Solubility | 0.045 mg/ml ; 0.000222 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 |
-6.11 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 |
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) |
2.42 |
* 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 |
---|---|---|
82% | With potassium acetate; acetic acid; In water; at 120℃; for 7h; | <strong>[60481-51-8]3,4-dimethylphenylhydrazine hydrochloride</strong> (8.7g, 50m mol), was dissolved in 100mlof glacial acetic acid, ethyl acetoacetate (6.5g, 50m mol) and sodium acetate (4.1g,50m mol) , 120 reflux reaction 7h, TLC detection of raw materials reaction completely.Evaporated under reduced pressureglacial acetic acid, was added 100ml of water, 100ml of ethyl acetate 4 times the combined ethyl acetatelayer was not over anhydrous sodium sulfate, and concentrated under reduced pressure to give 1- (3,4-dimethylphenyl) - 3- methyl-1hydrogen - pyrazol-5 (4 hydrogen) -one (8.3g, 82percent yield) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium nitrate; sodium hydrogencarbonate; | Take 11.5g82.4%) of 3'-amino-2'-hydroxybiphenyl-3-formic acid(VI) obtained in step ( 2), (6.8 g, 82.4%) 2-(3,4-dimethylphenyl)-1,2-dihydro-5-methyl-3H-pyrazol-3-one (VII) was added, condensation and cyclization reactions took place, and then Ethanolamine was added under the action of hydrogen to produce the synthesis reaction of Eltrombopag (IX); The 3'-amino-2' hydroxybiphenyl-3-formic acid and 2-(3,4-dimethylphenyl)-1,2-dihydro-5-methyl-3H-pyrazole- 3-one(VII) in step (3), reacted in a mixed solution of sodium nitrate and sodium bicarbonate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35.1% | With hydrogenchloride; sodium nitrite; In ethanol; water; at 0℃; for 0.5h; | 3) 190g of intermediate II and 2.86L of hydrochloric acid (2M) were weighed in a 10L four-necked flask, and 61.04g of 0.96 L aqueous solution of sodium nitrite was added to the system at a controlled temperature of 0 C. The starting material II was added at 0 C and stirred for 0.5 hours, 3.78 L of ethanol was added and the pH was adjusted to 7-8 with sodium bicarbonate. After stirring at room temperature for 24 hours, suction filtration was performed. The filter cake was slurried with 4.2 L of water for 0.5 h. The filter cake was acidified and slurried with 4.2 L of concentrated hydrochloric acid for 0.5 h. After the solution was dissolved under reflux, the temperature was lowered to 0 C, and the mixture was continuously stirred for 2 hours, and then filtered by suction. After the solid was put into air drying at 55 C for 12 hours, 128.72 g of a dark red solid was obtained. The yield was 35.1% and the purity was 99.1% |
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