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Chemical Structure| 195202-08-5

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Product Details of [ 195202-08-5 ]

CAS No. :195202-08-5
Formula : C13H18O5
M.W : 254.28
SMILES Code : CC[C@@H](C1=CC(OC)=C(OC)C(OC)=C1)C(O)=O
MDL No. :MFCD06245370
InChI Key :WBULUDGUWZFLMO-VIFPVBQESA-N
Pubchem ID :2771669

Safety of [ 195202-08-5 ]

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

Computational Chemistry of [ 195202-08-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 6
Fraction Csp3 0.46
Num. rotatable bonds 6
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 67.08
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

64.99 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.26
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

2.23
Log Po/w (WLOGP)?

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

2.29
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.

1.37
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

2.27
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.08

Water Solubility

Log S (ESOL):?

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

-2.67
Solubility 0.541 mg/ml ; 0.00213 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-3.23
Solubility 0.15 mg/ml ; 0.000589 mol/l
Class?

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

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

-3.0
Solubility 0.254 mg/ml ; 0.001 mol/l
Class?

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

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

Yes
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

No
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

No
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

No
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

No
Log Kp (skin permeation)?

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

-6.27 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

0.0
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.

0.56

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<0.0
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)

2.58

Application In Synthesis of [ 195202-08-5 ]

* 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.

  • Downstream synthetic route of [ 195202-08-5 ]

[ 195202-08-5 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 195202-08-5 ]
  • [ 18650-39-0 ]
  • [ 195202-09-6 ]
YieldReaction ConditionsOperation in experiment
84% Cpd9' (99 g, 0.39 mol) was dissolved in 1 L of dichloromethane, and <strong>[18650-39-0](S)-piperidine-2-carboxylic acid methyl ester hydrochloride</strong> (71.3 g, 0.40 mol), 2-chloro-1-methylpyridine Iodide (CMPI, 126.4 g, 0.50 mol), triethylamine (165 ml, 1.167 mol) was added dropwise, and the reaction was completed at room temperature for 2 h. TLC showed the reaction was completed and concentrated directly to give an oil. 50 ml of water, and then added LiOH (81.8 g, 3.41 mol), stirred at room temperature overnight, TLC showed the reaction was complete;Post-reaction treatment: 500 ml of water was added dropwise to the reaction, 40 C, concentrated to remove methanol, then added EA 500 ml and water 200 ml, and the extract was separated, and the organic phase was saturated NaHCO.3After washing, water was added and the aqueous phase was separated. The combined aqueous phases were acidified to pH 4 with 2N HCl solution and filtered to give white solid Cpd6' (120 g, yield 84%).
73% (lh) Step 8. Synthesis of [S-(R*,R*)]-l-[l-oxo-2-(3,4,5-trimethoxyphenyl)butyl]-2- piperdinecarboxylic acid (API 7362). A solution of AP17360 (10.0 g, 0.039 moles) in CH2C12 (100 mL) was treated with methyl-L- pipecolate hydrochloride (7.2 g, 0.04 moles) followed by 2-chloro-l-methylpyridinium iodide (12.77 g, 0.050 moles). The reaction mixture was then treated dropwise with triethylamine (16.66 mL, 0.120 moles) resulting in a 22C rise in the temperature of the reaction mixture. The solution was allowed to stir for 2 hours, after which time the CH2C12 was removed on a rotary evaporator, the residue (~ 50 mL volume) was dissolved in MeOH (60 mL), and the solution was treated with water (5 mL) followed by lithium hydroxide monohydrate (8.26 g, 0.197 moles). The mixture was stirred overnight then treated with water (20 mL) and the MeOH removed on a rotary evaporator at 40C. The resulting aqueous solution was treated with EtOAc (60 mL) followed by a saturated aqueous NaHC03 solution (60 mL) and the organic layer washed with water (10 mL). The combined aqueous layers were then acidified to pH 4 by careful addition of a 2N HC1 solution and the resulting suspension cooled to 10 C. The precipitate was filtered, triturated with a 1% aqueous citric acid solution (100 mL) and air dried under vacuum at 58 C to provide product, AP17362, (10.5 g, 73%): mp 173.5-174 "C; [ ] 2D +10.9 (c = 1.01, DMSO, 30 min); UV (MeOH) max 270 (epsilon 990), 232 (epsilon 11,161), 207 (epsilon 49,079) nm; NMR (DMSO- d6, 300 MHz) 6.55 (s, 2 H), 5.13 (d, J = 4.4 Hz, 1 H), 3.85-3.64 (m, 1 1 H), 2.77-2.70 (m, 1 H), 2.12 (d, J = 13.4 Hz, 1 H), 1.99-1.85 (m, 1 H), 1.65-1.55 (m, 4 H), 1.38-1.18 (m, 2 H), 0.84 (t, J = 7.2 Hz, 3 H); NMR (CD3OD, 300 MHz) 6.74 (s, 2 H), 5.43 (d, J = 4.0 Hz, 1 H), 4.13-3.83 (m, 1 1 H), 3.03 (td, J = 13.5, 3.0 Hz, 1 H), 2.44 (d, J = 13.8 Hz, 1 H), 2.24-2.14 (m, 1 H), 1.90-1.40 (m, 6 H) 1.09 (t, J = 7.3 Hz, 3 H); ,3C NMR (DMSO-d6, 75 MHz) 172.9, 172.2, 153.0, 136.2, 105.4, 60.2, 56.2, 56.0, 51.8, 49.4, 43.1, 28.5, 26.8, 25.3, 21.0, 12.8; 13C NMR (CD3OD, 75 MHz) 175.4, 174.5, 154.9, 137.5, 106.8, 61.5, 57.1, 53.9, 52.1, 45.2, 29.9, 28.2, 26.8, 22.3, 13.2; HRMS (FAB): (M-H)- calcd: 364.1760, meas: 364.1774. Anal. Calcd for C,9H2706: C, 62.45; H, 7.45; N, 3.83. Found: C, 62.32; H, 7.61 ; N, 3.88.
  • 2
  • [ 195202-08-5 ]
  • [ 18650-39-0 ]
  • C20H29NO6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 2-chloro-1-methyl-pyridinium iodide; triethylamine; In dichloromethane; at 12 - 25℃; (2S)-2-(3,4,5-Trimethoxyphenyl)butanoic acid 9 (93.0 g, 0.37 mol), Methyl (2S)- piperidinecarboxylate hydrochloride 11 (69.0 g, 0.38 mol, 1.1 eq.) and 2-chloro-1-methylpyridinium iodide (117.0 g, 0.46 mol, 1.3 eq.) were dissolved in DCM (720 ml_, 8.0 vol.) and cooled to 12 C. To the reaction mixture was added a solution of triethylamine (111.0 g, 1.10 mol, 3.0 eq.) in DCM (180 ml_, 2.0 vol.) while maintaining the internal temperature below 25 C. The reaction was then allowed to stir for 3-4 hours at 22 C. [IPC HPLC (C18: ACN/H20 10-90%, 20 min, 1 mL/min) 9: rrt 0.53 min, Intermediate ester: rrt 0.69, 14: rrt 0.58] Upon completion, the DCM was removed by rotary evaporation and exchanged for MeOH (225 ml_, 2.5 vol.). To the methanolic solution was added a solution of UOH.H2O (77.0 g, 1.83 mol, 5.0 eq.) in Dl water (225 ml_, 2.5 vol.) and the reaction was stirred for 12 hours at 22 C. Upon completion, as determined by IPC, additional water (180 ml_, 2.0 vol.) was added and the solution is vacuum distilled to remove methanol. EtOAc (450 ml_, 5.0 vol.) was added and the biphasic solution stirred vigorously for 10 minutes after which the phases were separated. The aqueous layer containing the product was removed and the organic phase was washed again with water (180 ml_, 2.0 vol.) and 10% NaHCC>3 sol. (360 ml_, 4.0 vol.). The combined aqueous layers were cooled to 4 C. A solution of 5M HCI was slowly added until the pH 4. The resulting slurry was stirred at 4 C for 3 hours then the solid was collected by vacuum filtration. The crude 14 (117.0 g, 0.32 mol) was dissolved in EtOH (1080 ml_, 12.0 vol.), heated and maintained at 50 C for 30 minutes. The ethanolic solution was then cooled to 0 C over 6 hours. The resulting crystalline solid is collected by vacuum filtration and washed with cold EtOH (90 ml_, 1.0 vol.). The product 14 (87.5 g, 0.24 mol, 66% yield) was obtained a colorless crystalline solid.Reverse phase HPLC analysis showed crystalline 14 (11.64 min) to be excellent purity with no detectable impurities. Chiral HPLC analysis shows crystalline 14 (32.58 min) to be excellent purity with no detectable chiral impurities.
 

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