Structure of (-)-Diethyl D-tartrate
CAS No.: 13811-71-7
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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. : | 13811-71-7 |
Formula : | C8H14O6 |
M.W : | 206.19 |
SMILES Code : | O=C(OCC)[C@@H](O)[C@H](O)C(OCC)=O |
MDL No. : | MFCD00064451 |
InChI Key : | YSAVZVORKRDODB-WDSKDSINSA-N |
Pubchem ID : | 117410 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.75 |
Num. rotatable bonds | 7 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 45.46 |
TPSA ? Topological Polar Surface Area: Calculated from |
93.06 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.33 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.29 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.17 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.71 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.22 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.21 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.47 |
Solubility | 69.3 mg/ml ; 0.336 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.2 |
Solubility | 12.9 mg/ml ; 0.0624 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
0.2 |
Solubility | 330.0 mg/ml ; 1.6 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 |
-7.76 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 |
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) |
3.14 |
* 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 |
---|---|---|
1.36 g (60%) | With N-ethyl-N,N-diisopropylamine; isopropylbenzene hydroperoxide;titanium(IV) isopropylate; In water; toluene; | Example 25 Asymmetric synthesis of (-)-2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl]sulphinyl]-1H-benzimidazole, (-)-(If). 2.1 g (6.3 mmol) of 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl]thio]-1H-benzimidazole was dissolved in 50 ml of toluene. To the solution was added 40 mul (2.2 mmol) of water, 1.6 ml (9.4 mmol) of (-)-diethyl D-tartrate and 1.1 ml (3.8 mmol) of titanium(IV) isopropoxide. The mixture was stirred for 60 minutes at 50 C. and then cooled to room temperature. 0.44 ml (2.6 mmol) of N,N-diisopropylethylamine and 1.1 ml (6.0 mmol) of cumene hydroperoxide (80%) were added. After stirring for 2 h at room temperature the mixture consisted of 9% sulphide, 4% sulphone and 86% sulphoxide according to achiral HPLC. To the mixture toluene (50 ml) was added and the resultant solution was extracted three times with an aqueous ammonia (12%) solution with a total volume of 150 ml. The combined aqueous layers were neutralized by the addition of concentrated acetic acid (30 ml). Thereafter, the workup procedure employed extraction, evaporation and flash chromatography yielding 1.62 g of the title compound with a purity of 99.9% (achiral analysis) and with an enantiomeric excess (e.e.) of 90% (chiral analysis). After treating the material with acetonitrile there was a precipitate that could be removed by filtration. Concentrating the filtrate afforded 1.36 g (60%) of the title compound as an oil with an optical purity of 91.5% e.e. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; isopropylbenzene hydroperoxide;titanium(IV) isopropylate; In 2,2,4-trimethylpentane; water; ethyl acetate; acetone; acetonitrile; | Example 8 Asymmetric synthesis followed by optical purification of (-)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulphinl]-1H-benzimidazole, (-)-(Ia) 1.6 kg (5.0 mol) of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methyl]thio]-1H-benzimidazole was dissolved in 5.01 of ethyl acetate. To the solution was added 31 ml (1.7 mol) of water. To the mixture was added 856 ml (5.0 mol) of (-)-diethyl D-tartrate, 744 ml (2.5 mol) of titanium(IV) isopropoxide and 435 ml (2.5 mol) of diisopropylethylamine at room temperature. The addition of 830 ml (4.5 mol) cumene hydroperoxide was then performed at 30° C. After stirring for one hour at 30° C. the reaction was complete. Chiral and achiral chromatographic analyses showed that the mixture consisted of 71.4percent sulphoxide with an enantiomeric excess (e.e.) of 72.9percent. The mixture was cooled to 10° C. and after addition of 1.7 l of isooctane, the product was extracted three times with an aqueous ammonia (12percent) solution with a total volume of 10 l. The combined aqueous phases were neutralised by addition of 1.5 l of concentrated acetic acid in the presence of ethyl acetate (3 l). The phases were separated and the aqueous phase was extracted with ethyl acetate (3 l). The solvent of the combined organic solutions was removed and at the end of the evaporation acetonitrile (1.5 l) was added to facilitate the removal of solvent. Acetone (2.5 l) was added to precipitate the racemate of omeprazole which was filtered off (254 g). HPLC-analyses (achiral and chiral columns) of the filtrate showed that this solution consited of 88percent sulphoxide with an optical purity of 96.3percent e.e. and thus the optical purity has been improved from 72.9percent e.e. to 96.3percent e.e. simply by one precipitation of racemic omeprazole. Further, a content analysis (HPLC) of the filtrate showed that the yield was 0.8 kg (46percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; isopropylbenzene hydroperoxide;titanium(IV) isopropylate; In toluene; | Example 5 Asymmetric synthesis of (-)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methyl]sulphinyl]-1H-benzimidazole, (-)-(Ia). 5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]-thio]-1H-benzimidazole (4.0 g, 12.1 mmol) was suspended in toluene (12 ml) (-)-Diethyl D-tartrate (0.17 ml, 1.0 mmol) and titanium(IV) isopropoxide (0.15 ml, 0.50 mmol) were added with stirring at 50° C. The mixture was stirred at 50° C. for 50 minutes and then N,N-diisopropylethylamine (0.085 ml, 0.50 mmol) was added at ca. 30° C. Then, cumene hydroperoxide (83percent, 2.1 ml, 11.9 mmol) was added and the mixture was stirred for 15 minutes at 30° C. The crude mixture was shown to consist of 3.6percent sulphide, 2.7percent sulphone and 93percent sulphoxide with an optical purity of 91percent e.e. The product was not isolated. |
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