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Chemical Structure| 279227-92-8 Chemical Structure| 279227-92-8

Structure of 279227-92-8

Chemical Structure| 279227-92-8

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Product Details of [ 279227-92-8 ]

CAS No. :279227-92-8
Formula : C11H21ClN2O4
M.W : 280.75
SMILES Code : O=C(N1[C@@H](C(OC)=O)CNCC1)OC(C)(C)C.[H]Cl
MDL No. :MFCD07366808
InChI Key :MESGHYLTRXYTHM-DDWIOCJRSA-N
Pubchem ID :45072201

Safety of [ 279227-92-8 ]

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

Computational Chemistry of [ 279227-92-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 0
Fraction Csp3 0.82
Num. rotatable bonds 5
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 76.37
TPSA ?

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

67.87 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

1.21
Log Po/w (WLOGP)?

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

0.41
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.

0.5
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

0.11
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.45

Water Solubility

Log S (ESOL):?

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

-2.01
Solubility 2.73 mg/ml ; 0.00971 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.

-2.23
Solubility 1.65 mg/ml ; 0.00586 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

-1.13
Solubility 20.9 mg/ml ; 0.0743 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

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

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.

-7.15 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.

0.55

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

1.0 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)

3.08

Application In Synthesis of [ 279227-92-8 ]

* 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 [ 279227-92-8 ]

[ 279227-92-8 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 279227-92-8 ]
  • [ 140937-52-6 ]
  • [ 892501-45-0 ]
YieldReaction ConditionsOperation in experiment
PREPARATIVE EXAMPLE 3; 1 ,1-Dimethyl-4-(8-chloro-5,11-dihvdro-ϖibenzoxepinor4,3-bipyridin-11-yl)-2(RV (methoxycarbonyl)piperazinecarboxylate The tricyclic alcohol (Biorg. & Med. Chem. Lett. 2521 , 1998) (7.01 gm, 28.3 mmol) was dissolved in toluene (100 mL) and SOCb (4 mL) was added while stirring under a dry N2 atmosphere. After 4 hrs, the mixture was evaporated to give a gum which was extracted with EtOAc and washed with 10% NaOH. The organics were dried over MgSO4, filtered and concentrated under reduced pressure to give a foamy solid. The resulting chloro-trycyclic compound was dissolved in dry DMF (100 mL) and the title compound from Preparative Example 2 (7. 94 gm, 28.29 mmol) was added followed by 4-methyl morpholine 15.54 mL, 141 mmol) and the mixture was stirred at room temperature under N2. After 24 hrs, the reaction mixture was concentrated and the residue dissolved in EtOAc and washed with brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure to give the title compond (9.5 g)
  • 2
  • [ 278790-00-4 ]
  • [ 279227-92-8 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; hydrogen;palladium on activated charcoal; In methanol; water; for 18.0h; PREPARATIVE EXAMPLE 2; The title compound from Preparative Example 1 (1.85 gm) was dissolved in MeOH (25 mL) and 1 N HCI (0.5 mL) in a hydrogenation vessel. The vessel was flushed with N2 and 10% Pd/C (0.38 gm, 50% weight with water) was added. The mixture was hydrogenated at 55 psi of H2 for 18 hours. When the reaction was complete (TLC, 25% EtOAc/Hexane) the catalyst was filtered off and the filtrate was evaporated to dryness to give the title compound (1.3 gm).
  • 3
  • [ 279227-92-8 ]
  • [ 24424-99-5 ]
  • [ 637027-24-8 ]
YieldReaction ConditionsOperation in experiment
95% With sodium carbonate; In 1,4-dioxane; water; for 18.0h; Synthesis of (R)-Piperazine-l,2,4-tricarboxylic acid 1,4-di-tert-butyl ester 2-methyl ester [A037] To a stirred suspension of (R)-l-N-Boc-piperazine-2-carboxylic acid methyl ester hydrochloride (2 g, 7.12 mmol) and a2CC>3 (2.26 g, 21.4 mmol) in dioxane (16ml) and water (4 ml) at 0 C was added Di-tert-butyl-dicarbonate (1.55 g, 7.12 mmol). After 18 hours all solvents were removed in vacuo and the resulting residue partitioned between DCM and water. The organic phase was collected and evaporated to give a colourless oil. Purification by column chromatography (0-30% EtOAc:cyclohexane) gave the title compound [A037] as a white powder (2.33 g, 95%). 1H-NMR (1H, 300MHz, CDC13): 5.30 (1H, s), 4.72 (1H, s, br), 4.54 (1H, t, br), 4.08-3.80 (1H, m), 3.73 (3H, s), 3.27-2.73 (3H, m), 1.44 (18H, s).
 

Historical Records

Technical Information

Categories

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[ 279227-92-8 ]

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Related Parent Nucleus of
[ 279227-92-8 ]

Piperazines

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