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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
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Structure of 29509-06-6
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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.
4.5
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CAS No. : | 29509-06-6 |
Formula : | C6H9NO |
M.W : | 111.14 |
SMILES Code : | CC(C)C(=O)CC#N |
MDL No. : | MFCD05664144 |
InChI Key : | VKZGTORDNRVMIN-UHFFFAOYSA-N |
Pubchem ID : | 10129921 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H301-H311-H331 |
Precautionary Statements: | P261-P280-P301+P310-P311 |
Class: | 6.1 |
UN#: | 2810 |
Packing Group: | Ⅲ |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.67 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 30.91 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.86 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.11 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.88 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.13 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.35 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.89 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.87 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.95 |
Solubility | 12.4 mg/ml ; 0.112 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.32 |
Solubility | 5.29 mg/ml ; 0.0476 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.08 |
Solubility | 9.22 mg/ml ; 0.083 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 |
-6.35 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) |
1.33 |
* 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 hydrazine; In ethanol; at 20℃; for 3h; | A solution of 4-methyl-3-oxopentanenitrile (25 g, 225 mmol) and hydrazine (6.75 mL, 215 mmol) in ethanol (250 mL) was stirred at room temperature for 3 h, at which point LC/MS indicated exclusively product remained. The mixture was concentrated on a rotary evaporator followed by under high vacuum to give the desired product (27.8 g, 99%) as a yellow semisolid that was used without further purification. |
99% | With hydrazine; In ethanol; | 5-Isopropyl-1H-pyrazol-3-ylamine. A solution of 4-methyl-3-oxopentanenitrile (25 g, 225 mmol) and hydrazine (6.75 mL, 215 mmol) in ethanol (250 mL) was stirred at room temperature for 3 h, at which point LC/MS indicated exclusively product remained. The mixture was concentrated on a rotary evaporator followed by under high vacuum to give the desired product (27.8 g, 99%) as a yellow semisolid that was used without further purification. |
59% | With hydrazine hydrate; In ethanol; at 0℃; for 4h;Reflux; | Step-2: Synthesis of 5-isopropyl-1H-pyrazol-3-amine, Compound (ii) To a solution of 4-methyl-3-oxopentanenitrile (15 g, 135 mmol) in EtOH (150 mL) was added hydrazine hydrate (7.30 g, 146 mmol) slowly at 0 C. The reaction mixture was heated to reflux for 4 h. Removal of EtOH under reduced pressure gave an oily residue that was dissolved in EtOAc (200 mL) and washed with freshly prepared brine (2*50 mL). The organic layer was dried over anhydrous sodium sulfate. Removal of EtOAc gave 5-isopropyl-1H-pyrazol-3-amine, Compound (ii) (10 g, 59% yield). 1H NMR (400 MHz, CDCl3) δ (ppm): 1.22 (d, 6H), 2.80-2.92 (m, 1H), 4.80 (brs, 3H), 5.41 (s, 1H). |
With hydrazine; In ethanol; at 70℃; for 12h; | A mixture of a portion (0.6 g) of the material so obtained, hydrazine hydrate (0.288 ml) and ethanol (45 ml) was heated at 700C for 12 hours. The solvent was evaporated and the residue was purified by column chromatography on silica using a 19:1 mixture of methylene chloride and methanol as eluent. There was thus obtained the required starting material <n="115"/>(0.574 g); 1H NMR: (DMSOd6) 1.13 (d, 6H), 2.76 (m, IH), 4.31 (br s, 2H), 5.17 (br s, IH), 11.05 (br s, IH); Mass Spectrum: M+H+ 126. | |
With hydrazine; In ethanol; water; at 70℃; for 12h; | A mixture of a portion (0.6 g) of the material so obtained, hydrazine hydrate (0.288 ml) and ethanol (45 ml) was heated at 70 C. for 12 hours. The solvent was evaporated and the residue was purified by column chromatography on silica using a 19:1 mixture of methylene chloride and methanol as eluent. There was thus obtained the required starting material (0.574 g); 1H NMR: (DMSOd6) 1.13 (d, 6H), 2.76 (m, 1H), 4.31 (br s, 2H), 5.17 (br s, 1H), 11.05 (br s, 1H); Mass Spectrum: M+H+ 126. | |
With hydrazine; In ethanol; at 60℃; for 24h; | General procedure: A solution of 50 mg (0.34 mmol) of 3-oxo-3-phenylpropanenitrile and 11.6 mg (0.36 mmol) of hydrazine and 0.024 mL of acetic acid (0.37 mmol) in 3 mL of anhydrous ethanol was heated at 60 C for 24 hr. The mixture was cooled to ambient temperature and the solvent removed in vacuo. The residue was taken up in ethyl acetate, washed with saturated sodium bicarbonate. The organic layer was washed with brine and dried over MgSO4, filtered and evaporated. The solid residue waswashedwithethyl ether and dried in vacuo to give 45 mg (82%) of 3-phenyl-1H-pyrazol-5-amine. | |
With hydrazine hydrate; In ethanol; at 0 - 70℃; for 3h; | General procedure: To a solution of 3-cyclopropyl-3-oxopropanenitrile (10 g, 91.7 mmol)) in ethanol (200 mL) was dropwise added hydrazine monohydrate (7.74 mL, 160 mmol) at 0 . The resulting mixture was heated under reflux for 3 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was partitioned with ethyl acetate and water. The organic layer was dried over sodium sulfate, filtered and concentrated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With hydrogenchloride; In ethanol; for 18h;Reflux; | Intermediate A18: 1-(3,4-Dimethylphenyl)-3-isopropyl-1 H-pyrazol-5-amine. Intermediate A18 To a solution of <strong>[60481-51-8](3,4-dimethylphenyl)hydrazine hydrochloride</strong> (3.0 g, 17 mmol) and 4-methyl- 3-oxopentanenitrile (2.3 mL, 19 mmol) in EtOH (20 mL) was added concentrated hydrochloric acid (1.7 mL, 12 M, 20 mmol). The reaction mixture was heated to reflux for 18 hr and was then cooled to RT and evaporated in vacuo. The residue was partitioned between DCM (50 mL) and water (20 mL). The aq phase was separated and was extracted with DCM (2 x 50 mL). The combined organic extracts were dried and evaporated in vacuo and the residue was purified by flash column chromatography (Si02, 80 g, 0-100percent Et20 in isohexane, gradient elution) to afford the title compound, Intermediate A18 as an orange oil (2.69 g, 67percent); Rl 1.49 min (Method 2 acidic); m/z 230 (M+H)+, (ES+). |
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