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Chemical Structure| 586966-54-3 Chemical Structure| 586966-54-3

Structure of tert-Buthyl Pitavastatin
CAS No.: 586966-54-3

Chemical Structure| 586966-54-3

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Synonyms: tert-Butyl pitavastatin

4.5 *For Research Use Only !

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Product Details of [ 586966-54-3 ]

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

Safety of [ 586966-54-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 586966-54-3 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

79.65 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

4.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

4.83
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

6.02
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

3.88
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

6.83
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

5.11

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-5.52
Solubility 0.00144 mg/ml ; 0.00000301 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-6.24
Solubility 0.000277 mg/ml ; 0.000000581 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-7.69
Solubility 0.00000977 mg/ml ; 0.0000000205 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

Yes
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

Yes
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

Yes
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.78 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

1.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<3.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

4.72

Application In Synthesis of [ 586966-54-3 ]

* 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.

  • Upstream synthesis route of [ 586966-54-3 ]

[ 586966-54-3 ] Synthesis Path-Upstream   1~15

  • 1
  • [ 147489-06-3 ]
  • [ 586966-54-3 ]
YieldReaction ConditionsOperation 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
References: [1] Patent: US2013/72688, 2013, A1, . Location in patent: Paragraph 0060-0062.
[2] Patent: US2012/16129, 2012, A1, . Location in patent: Page/Page column 13-14.
[3] Patent: WO2014/108795, 2014, A2, . Location in patent: Page/Page column 19; 20.
[4] Patent: JP6231262, 2017, B2, . Location in patent: Paragraph 0030-0032.
  • 2
  • [ 121660-11-5 ]
  • [ 586966-54-3 ]
References: [1] Patent: US2012/16129, 2012, A1, .
[2] Patent: WO2012/63254, 2012, A1, .
[3] Patent: JP6231262, 2017, B2, .
  • 3
  • [ 765-43-5 ]
  • [ 586966-54-3 ]
References: [1] Patent: US2012/16129, 2012, A1, .
[2] Patent: US2012/16129, 2012, A1, .
  • 4
  • [ 32249-35-7 ]
  • [ 586966-54-3 ]
References: [1] Patent: US2012/16129, 2012, A1, .
[2] Patent: US2012/16129, 2012, A1, .
  • 5
  • [ 121659-86-7 ]
  • [ 586966-54-3 ]
References: [1] Patent: US2012/16129, 2012, A1, .
[2] Patent: US2012/16129, 2012, A1, .
  • 6
  • [ 124655-09-0 ]
  • [ 586966-54-3 ]
References: [1] Patent: WO2014/108795, 2014, A2, .
[2] Patent: WO2014/108795, 2014, A2, .
  • 7
  • [ 121660-37-5 ]
  • [ 586966-54-3 ]
References: [1] Patent: WO2012/63254, 2012, A1, .
  • 8
  • [ 154057-56-4 ]
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References: [1] Patent: WO2012/63254, 2012, A1, .
  • 9
  • [ 1054627-26-7 ]
  • [ 586966-54-3 ]
References: [1] Patent: WO2014/108795, 2014, A2, .
  • 10
  • [ 141942-89-4 ]
  • [ 586966-54-3 ]
References: [1] Patent: WO2014/108795, 2014, A2, .
  • 11
  • [ 1353750-24-9 ]
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References: [1] Patent: WO2014/108795, 2014, A2, .
  • 12
  • [ 154026-93-4 ]
  • [ 586966-54-3 ]
References: [1] Patent: KR101528359, 2015, B1, .
  • 13
  • [ 154026-92-3 ]
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References: [1] Patent: KR101528359, 2015, B1, .
  • 14
  • [ 540-88-5 ]
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References: [1] Patent: KR101528359, 2015, B1, .
  • 15
  • [ 1234331-56-6 ]
  • [ 586966-54-3 ]
References: [1] Patent: JP6231262, 2017, B2, .
 

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