Structure of tert-Buthyl Pitavastatin
CAS No.: 586966-54-3
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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: tert-Butyl pitavastatin
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| CAS No. : | 586966-54-3 |
| Formula : | C29H32FNO4 |
| M.W : | 477.57 |
| SMILES Code : | O=C(OC(C)(C)C)C[C@H](O)C[C@H](O)/C=C/C1=C(C2=CC=C(F)C=C2)C3=CC=CC=C3N=C1C4CC4 |
| Synonyms : |
tert-Butyl pitavastatin
|
| MDL No. : | MFCD12755990 |
| InChI Key : | RCARMBIYAHBUHR-UQECUQMJSA-N |
| Pubchem ID : | 10299312 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302-H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
| Num. heavy atoms | 35 |
| Num. arom. heavy atoms | 16 |
| Fraction Csp3 | 0.38 |
| Num. rotatable bonds | 10 |
| Num. H-bond acceptors | 6.0 |
| Num. H-bond donors | 2.0 |
| Molar Refractivity | 136.6 |
| TPSA ? Topological Polar Surface Area: Calculated from |
79.65 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
4.0 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.83 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
6.02 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.88 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
6.83 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
5.11 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-5.52 |
| Solubility | 0.00144 mg/ml ; 0.00000301 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-6.24 |
| Solubility | 0.000277 mg/ml ; 0.000000581 mol/l |
| Class? Solubility class: Log S scale |
Poorly soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-7.69 |
| Solubility | 0.00000977 mg/ml ; 0.0000000205 mol/l |
| Class? Solubility class: Log S scale |
Poorly 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) |
Yes |
| 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) |
Yes |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
Yes |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
Yes |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.78 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 |
1.0 |
| 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<3.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
4.72 |
* 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 |
|---|---|---|
| 88.4% | With hydrogenchloride; water In acetonitrile for 3 h; Large scale | The compound prepared in Example 1 (1.5 kg) was added to acetonitrile (16 L). A mixed solution of a 35percent HCl solution (0.91 kg) and purified water (9.5 kg) was slowly added over 2 hours to the mixture under stirring. The reaction mixture was stirred for additional 1 hour. After confirming with HPLC that the starting material was exhausted, the reaction was quenched. The reaction mixture was neutralized with sodium bicarbonate and then extracted with ethyl acetate. The separated organic layer was washed with a sodium chloride solution (1.5 kg) and then concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (1.5 L) and then hexane (9 L) was slowly added thereto. The reaction mixture was cooled to about 10° C. and then stirred for 2 hours. The resulting precipitate was isolated by filtering under reduced pressure and then dried under reduced pressure at about 50° C. to give the titled compound (1.22 kg) as a white crystalline form (Yield: 88.4percent).[0062]HPLC percent Area: 98.555percent |
| 27 g | With hydrogenchloride; water In acetonitrile at 25 - 55℃; | EXAMPLE-lOPREPARATION OF tert.-BUTYL (3R,5S,6E)-7-[2-CYCLOPROPYL-4-(4-• FLUOROPHENYL)QUINOLIN-3-YL]-3,5-DfflYDROXY-6-HEPTENOATE [tertBUTYL PITAVASTATIN]Diprotected tert-butyl Pitavastatin (30 g, 0.058 mole) was suspended in acetonitrile (210 ml) and water (70 ml) at 25-30°C. The pH of the reaction mass was adjusted to 2.5 with dilute hydrochloric acid (0.1 molar). Thereafter, the reaction mass was heated to 50-55°C and progress of the reaction was monitored by HPLC After completion of reaction, pH of the reaction mass was adjusted to 8.5 with aqueous ammonia and stirred for 30 mm. Product was filtered and dried at 40-45°C under reduced pressure to obtain title compound.Yield: 27gChromatographic Purity (by HPLC): 99.6percent, Lactone diastereomer: 0.09percent |

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