Structure of mono-Methyl hydrogen succinate
CAS No.: 3878-55-5
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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. : | 3878-55-5 |
Formula : | C5H8O4 |
M.W : | 132.11 |
SMILES Code : | C(C(OC)=O)CC(O)=O |
MDL No. : | MFCD00002788 |
InChI Key : | JDRMYOQETPMYQX-UHFFFAOYSA-N |
Pubchem ID : | 77487 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.6 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 29.21 |
TPSA ? Topological Polar Surface Area: Calculated from |
63.6 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.08 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.02 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.02 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.13 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.14 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.17 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.41 |
Solubility | 51.7 mg/ml ; 0.391 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.91 |
Solubility | 16.3 mg/ml ; 0.124 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.1 |
Solubility | 104.0 mg/ml ; 0.785 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 |
No |
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 |
-7.09 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 |
0.56 |
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) |
1.56 |
* 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 |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In chloroform; for 24h; | General procedure: A mixture of 4-(2-chlorophenyl)thiazol-2-amine (500 mg, 2.37 mmol), DMAP (13.27 mg, 0.12 mmol), EDCI (682.43 mg, 3.55 mmol) and 4-methoxy-4-oxobutanoic acid (470.3 mg, 3.55 mmol) in chloroform (20 mL) was stirred at room temperature for 24 h. The solution was filtered, and filtrate was washed with water. The organic phase was dried (Na2SO4) and evaporated to dryness. The residue was purified by flash chromatography over silica gel eluting with CH2Cl2:EtOAC (80:1) yielded 280 mg (36.3% yield) to 5b. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36.3% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In chloroform; for 24h; | General procedure: A mixture of <strong>[21344-90-1]4-(2-chlorophenyl)thiazol-2-amine</strong> (500 mg, 2.37 mmol), DMAP (13.27 mg, 0.12 mmol), EDCI (682.43 mg, 3.55 mmol) and 4-methoxy-4-oxobutanoic acid (470.3 mg, 3.55 mmol) in chloroform (20 mL) was stirred at room temperature for 24 h. The solution was filtered, and filtrate was washed with water. The organic phase was dried (Na2SO4) and evaporated to dryness. The residue was purified by flash chromatography over silica gel eluting with CH2Cl2:EtOAC (80:1) yielded 280 mg (36.3percent yield) to 5b. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of 4-methoxy-4-oxobutanoic acid (9.7 g, 73.5 mmol) in toluene (368 mL) was added diphenylphosphoryl azide (20.2 g, 73.5 mmol) followed by TEA (12.4 g, 122.7 mmol). The reaction was stirred at RT for 30 min then <strong>[58483-95-7]5-amino-2-chloroisonicotinic acid</strong> (8.47 g, 49 mmol) was added. The reaction was heated at reflux for 6 h, cooled to RT then diluted with EA (300 mL). The mixture was washed with brine (300 mL) and out of the organic layer precipitated a solid which was filtered. The separated aqueous layer was acidified to PH 5 by adding aq. 2N HC1 and a precipitate formed. The solid was filtered and combined with the organic layer solid. The combined solids were dried to give 2-chloro-5-(3-(3-methoxy-3-oxopropyl)ureido) isonicotinic acid (26 g, >100percent yield) as brown semi-solid. LCMS: MH+ 302 MH+ and TR = 2.752 min. Used without further purification. |
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