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Chemical Structure| 91188-13-5 Chemical Structure| 91188-13-5

Structure of 91188-13-5

Chemical Structure| 91188-13-5

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Product Details of [ 91188-13-5 ]

CAS No. :91188-13-5
Formula : C8H16N2O2
M.W : 172.22
SMILES Code : O=C(OC(C)(C)C)NC1CNC1
MDL No. :MFCD01861759
InChI Key :NEMXVXVJGXZDRR-UHFFFAOYSA-N
Pubchem ID :1519405

Safety of [ 91188-13-5 ]

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

Computational Chemistry of [ 91188-13-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 0
Fraction Csp3 0.88
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 49.69
TPSA ?

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

50.36 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.21
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

0.34
Log Po/w (WLOGP)?

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

0.1
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.

0.24
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

0.26
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.63

Water Solubility

Log S (ESOL):?

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

-0.86
Solubility 23.9 mg/ml ; 0.139 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-0.96
Solubility 18.8 mg/ml ; 0.109 mol/l
Class?

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

Very 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

-1.48
Solubility 5.73 mg/ml ; 0.0333 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.

-7.11 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

1.0
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<1.0
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)

2.0

Application In Synthesis of [ 91188-13-5 ]

* 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 [ 91188-13-5 ]

[ 91188-13-5 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 15996-84-6 ]
  • [ 530-62-1 ]
  • [ 91188-13-5 ]
  • [ 920320-49-6 ]
YieldReaction ConditionsOperation in experiment
67% To a solution of l-[4-(trifluoromethyl)phenyl]ethylamine (1.Og, 5.2 mmol) in dichloromethane (20 ml) at 3O0C was added a suspension of 1,1 '-carbonyl diimidazole (0.86g, 5.2mmol) in dichloromethane (7 ml) and the reaction was stirred at 3O0C for 1 hour. A suspension of azetidine-3-yl-carbamic acid terf-butyl ester (0.89g, 5.2mmol) in dichloromethane (5ml) was added and the reaction stirred at 30 for 5 hours. The reaction was cooled to room temperature (r.t.) and the product obtained by filtration as a white solid. Yield 1.35 g (67%): HPLC retention time, 3.56min (Solvent: CH3CN/H2O/0.05% NH3, 5-95% gradient H2O-6min. Column: Xterra 50 x 4.60 i.d., Cl 8 reverse phase. Flow rate: 1.5mL/min.). Mass spectrum (ES+) m/z 388 (M + H).
  • 2
  • [ 60211-57-6 ]
  • [ 530-62-1 ]
  • [ 91188-13-5 ]
  • 3,5-dichlorobenzyl 3-((tert-butoxycarbonyl)amino)azetidine-1-carboxylate [ No CAS ]
  • 3
  • [ 1211534-25-6 ]
  • [ 91188-13-5 ]
  • C14H20ClN3O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; bis(dibenzylideneacetone)-palladium(0); In 1,4-dioxane; at 100℃; for 4h; In a reaction vial, fert-butyl 3-aminoazetidine-l-carboxylate (CAS No. 217806- 26-3) (938 mg, 4.49 mmol), tris(dibenzylideneacetone)dipalladium (206mg, 0.22mmol), BINAP (210mg, 0.34mmol), cesium carbonate (2.21g, 6.74mmol), 4-bromo-5-chloro-2- methoxypyridine (CAS No. 121 1534-25-6) (500.mg, 2.25mmol) and 1,4-dioxane (18mL) were added. The vial was capped and purged with nitrogen. The reaction vial was then heated to 100 °C for 4 h. The mixture was filtered through a pad of Celite which was washed with EtOAc/DCM (1 : 1 ; 2xl00mL). The filtrate was concentrated. Purification using flash column chromatography on silica gel (80G column, 0-50percent EtOAc/hexanes) to provide Boc-amine as an off white powder (570 mg). The material was dissolved in 1,4-dioxane (1 lmL) and hydrochloric acid (4M in 1,4-dioxane) (3mL, 12mmol) was added. The mixture was stirred at r.t. until the deprotection was complete. Solvent was removed to provide the desired product as a white powder, bis-HCl salt (555mg, 86percent yield over two steps). ES-MS [M+1]+ : 214.2.
  • 4
  • [ 22929-52-8 ]
  • [ 91188-13-5 ]
  • 1-(tetrahydrofuran-3-yl)azetidin-3-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium tris(acetoxy)borohydride; In dichloromethane; (0372) Tert-butyl azetidin-3-ylcarbamate (0.550 g), <strong>[22929-52-8]dihydrofuran-3(2H)-one</strong> (0.412 g) and sodium triacetoxyborohydride (1.015 g) were stirred together in dichloromethane (5 ml). After stirring overnight, the reaction was poured into saturated aqueous NaHCO3 solution (25 ml) and extracted with dichloromethane (50 ml). The organic layer was washed with brine (25 ml), dried over magnesium sulfate, filtered, and concentrated. Silica gel chromatography (GraceResolv 12 g) eluting with a gradient of 0.5percent to 7.5percent methanol/dichloromethane over 30 minutes gave tert-butyl 1-(tetrahydrofuran-3-yl)azetidin-3-ylcarbamate. The resulting material was treated with HCl/dioxane for 1 hour, and then concentrated to give the title compound.
 

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Technical Information

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