Structure of Ethyl 3-oxopentanoate
CAS No.: 4949-44-4
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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.
Synonyms: Ethyl Propionylacetate
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CAS No. : | 4949-44-4 |
Formula : | C7H12O3 |
M.W : | 144.17 |
SMILES Code : | CCC(CC(OCC)=O)=O |
Synonyms : |
Ethyl Propionylacetate
|
MDL No. : | MFCD00009317 |
InChI Key : | UDRCONFHWYGWFI-UHFFFAOYSA-N |
Pubchem ID : | 78656 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.71 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 37.25 |
TPSA ? Topological Polar Surface Area: Calculated from |
43.37 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.9 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.72 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.92 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.64 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.13 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.06 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.86 |
Solubility | 20.0 mg/ml ; 0.139 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.21 |
Solubility | 8.91 mg/ml ; 0.0618 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.48 |
Solubility | 4.74 mg/ml ; 0.0329 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 |
-6.67 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) |
1.61 |
* 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 |
---|---|---|
95% | With piperidine; acetic acid; In acetonitrile; at 80.0℃; for 4.0h; | Step A: A mixture of tert-butyl 4-(4-formyl-3-hydroxyphenyl)piperazine-l- carboxylate (3.0 g, 9.8 mmol, prepared in Example 1, Part 2), ethyl 3-oxopentanoate (1.62 mL, 11.3 mmol), AcOH (650 mu, 12 mmol), piperidine (1.1 mL, 11.3 mmol), and CH3CN (24 mL) were heated at 80 C for 4 h. The reaction mixture was partitioned between CH2CI2 and H2O. The organic layer was dried over MgS04, filtered, and concentrated under vacuum. The residue was purified by silica gel column chromatography (10%> EtOAc in CH2CI2), followed by ether trituration, yielding tert-butyl 4-(2-oxo-3-propionyl-2H-chromen-7-yl)piperazine-l-carboxylate (3.6 g, 95%) as a yellow solid. 1H NMR (500 MHz, CDC13): delta 8.49 (1H, s), 7.50 (1H, d, J= 8.5 Hz), 6.83 (1H, dd, J= 8.5 Hz, 2.5 Hz), 6.67 (1H, d, J= 2 Hz), 3.63 (4H, m), 3.47 (4H, m), 3.16 (2H, q, J= 7 Hz), 1.52 (9H, s), 1.19 (3H, t, J= 7 Hz). |
95% | With piperidine; acetic acid; In acetonitrile; at 80.0℃; for 4.0h; | Step A: A mixture of <strong>[1446332-69-9]tert-butyl 4-(4-formyl-3-hydroxyphenyl)piperazine-1-carboxylate</strong> (3.0 g, 9.8 mmol, prepared in Example 1, Part 2), ethyl 3-oxopentanoate (1.62 mL, 11.3 mmol), AcOH (650 muL, 12 mmol), piperidine (1.1 mL, 11.3 mmol), and CH3CN (24 mL) were heated at 80 C. for 4 h. The reaction mixture was partitioned between CH2Cl2 and H2O. The organic layer was dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by silica gel column chromatography (10% EtOAc in CH2Cl2), followed by ether trituration, yielding tert-butyl 4-(2-oxo-3-propionyl-2H-chromen-7-yl)piperazine-1-carboxylate (3.6 g, 95%) as a yellow solid. 1H NMR (500 MHz, CDCl3): delta 8.49 (1H, s), 7.50 (1H, d, J=8.5 Hz), 6.83 (1H, dd, J=8.5 Hz, 2.5 Hz), 6.67 (1H, d, J=2 Hz), 3.63 (4H, m), 3.47 (4H, m), 3.16 (2H, q, J=7 Hz), 1.52 (9H, s), 1.19 (3H, t, J=7 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With polyphosphoric acid; at 120℃; for 2.0h; | To a solution of 6-choro-3-amino-4,5-dimethylpyridazine (550 mg) in polyphosphoric acid (4 mL) was added ethyl 3-oxopentanoate {913 pL). The mixture was heated to 85 “C for 1 hour, then 120 C for 1 hour. While hot, the mixture was slowly transferred to a stirred solution of saturated aqueous NaHCC {~150 mL) and chloroform/IPA (4:1) (50 mL). Upon complete addition, the mixture was stirred for 10 minutes then the organic layer was isolated. The aqueous layers was further extracted with chloroform/IPA (4:1) (x3) and the organic layers were pooled, dried over MgS04, filtered, and concentrated under vacuum. Upon cooling, a solid precipitate was observed. Hexanes was added, the suspenion was sonicated, the solid was collected by vacuum filtration, and washed with hexanes to provide the title compound (469 mg, 57% yield) >95% dean by LCMS. NMR (400 MHz, CDC ) d 6.50 (s, 1H), 2.70 (q, J 7.6 Hz, 2H), 2.61 (s,3H), 2.48 (s, 3H), 1.30 (†., J = 7.6 Hz, 3H). ES-MS [M+l]+: 238. |
57% | With polyphosphoric acid; at 120℃; for 2.0h; | To a solution of 6-choro-3-amino-4,5-dimethylpyridazine (550 mg) in polyphosphoric acid (4 mL) was added ethyl 3-oxopentanoate {913 pL). The mixture was heated to 85 “C for 1 hour, then 120 C for 1 hour. While hot, the mixture was slowly transferred to a stirred solution of saturated aqueous NaHCC {~150 mL) and chloroform/IPA (4:1) (50 mL). Upon complete addition, the mixture was stirred for 10 minutes then the organic layer was isolated. The aqueous layers was further extracted with chloroform/IPA (4:1) (x3) and the organic layers were pooled, dried over MgS04, filtered, and concentrated under vacuum. Upon cooling, a solid precipitate was observed. Hexanes was added, the suspenion was sonicated, the solid was collected by vacuum filtration, and washed with hexanes to provide the title compound (469 mg, 57% yield) >95% dean by LCMS. NMR (400 MHz, CDC ) d 6.50 (s, 1H), 2.70 (q, J 7.6 Hz, 2H), 2.61 (s,3H), 2.48 (s, 3H), 1.30 (†., J = 7.6 Hz, 3H). ES-MS [M+l]+: 238. |
57% | With polyphosphoric acid; at 120℃; for 2.0h; | To a solution of 6-choro-3-amino-4,5-dimethylpyridazine (550 mg) in polyphosphoric acid (4 mL) was added ethyl 3-oxopentanoate {913 pL). The mixture was heated to 85 “C for 1 hour, then 120 C for 1 hour. While hot, the mixture was slowly transferred to a stirred solution of saturated aqueous NaHCC {~150 mL) and chloroform/IPA (4:1) (50 mL). Upon complete addition, the mixture was stirred for 10 minutes then the organic layer was isolated. The aqueous layers was further extracted with chloroform/IPA (4:1) (x3) and the organic layers were pooled, dried over MgS04, filtered, and concentrated under vacuum. Upon cooling, a solid precipitate was observed. Hexanes was added, the suspenion was sonicated, the solid was collected by vacuum filtration, and washed with hexanes to provide the title compound (469 mg, 57% yield) >95% dean by LCMS. NMR (400 MHz, CDC ) d 6.50 (s, 1H), 2.70 (q, J 7.6 Hz, 2H), 2.61 (s,3H), 2.48 (s, 3H), 1.30 (†., J = 7.6 Hz, 3H). ES-MS [M+l]+: 238. |