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Chemical Structure| 16066-84-5 Chemical Structure| 16066-84-5

Structure of 16066-84-5

Chemical Structure| 16066-84-5

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Product Details of [ 16066-84-5 ]

CAS No. :16066-84-5
Formula : C6H13NO2
M.W : 131.17
SMILES Code : O=C(OC(C)(C)C)NC
MDL No. :MFCD08899404
InChI Key :JHLVEBNWCCKSGY-UHFFFAOYSA-N
Pubchem ID :527635

Safety of [ 16066-84-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H312-H315-H319-H332-H335
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Computational Chemistry of [ 16066-84-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.83
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 35.47
TPSA ?

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

38.33 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.06
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

0.93
Log Po/w (WLOGP)?

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

1.14
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.

0.8
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

0.08
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.0

Water Solubility

Log S (ESOL):?

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

-1.04
Solubility 11.9 mg/ml ; 0.091 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.

-1.32
Solubility 6.26 mg/ml ; 0.0477 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

-1.18
Solubility 8.63 mg/ml ; 0.0658 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.

-6.44 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)

1.53

Application In Synthesis of [ 16066-84-5 ]

* 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 [ 16066-84-5 ]

[ 16066-84-5 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 16066-84-5 ]
  • [ 851386-34-0 ]
  • C11H14F2N2O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; at 100℃; for 13.5h; Compound a70 (1.0g, 4.15mmol) was dissolved in dioxane (16 mL), tert-butyl methyl carbamate (653mg, 4.98mmol), 2- dicyclohexylphosphino-2 ', 4', 6'-triisopropyl biphenyl (297mg, 0.622mmol), potassium phosphate (2.20g, 10.73mmol)And tris (dibenzylideneacetone) palladium(190mg, 0.207mmol) was added, and the mixture was stirred for 5 hours at 100°C .Tertiary butyl methyl carbamate (218mg, 1.66mmol),2-dicyclohexyl phosphino-2 ', 4', 6'-triisopropyl biphenyl(99mg, 0.207mmol),Potassium phosphate (0.73g, 3.57mmol)And tris (dibenzylideneacetone) palladium (0)(63.3mg, 0.069mmol) was added and stirred for 3 hours and a half.Tertiary butyl methyl carbamate (435mg, 3.32mmol),2-dicyclohexyl phosphino-2 ', 4', 6'-triisopropyl-biphenyl (99 mg, 0.207 mmol) and tris (dibenzylideneacetone) palladium (0) (63.3 mg, 0.069 mmol) was added to 5 hours It was semi-stirring.Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography - (hexanes-ethyl acetate) to give compound a71 (0.75 g, 74percent yield).
74% With potassium phosphate; XPhos; In 1,4-dioxane; at 100℃; for 13.5h; Step 1 Preparation of Compound c71 (0551) Compound c70 (1.0g, 4.15mmol) was dissolved in dioxane (16mL), and tertiary butyl methyl carbamate (653mg, 4.98mmol), 2- dicyclohexylphosphino-2 ', 4' , 6'-triisopropyl-biphenyl (297mg, 0.622mmol), potassium phosphate (2.20g, 10.73mmol) and tris (dibenzylideneacetone) palladium (190mg, 0.207mmol) were added to the mixture at 100 °C for 5 hours. Tertiary butyl methyl carbamate (218mg, 1.66mmol), 2-dicyclohexylphosphino-2 ', 4', 6'-triisopropyl biphenyl (99mg, 0.207mmol), potassium phosphate (0.73g, 3.57mmol) and tris (dibenzylideneacetone) palladium (0) (63.3mg, 0.069mmol) were added to the mixture and the mixture was stirred for 3 hours. Tertiary butyl methyl carbamate (435mg, 3.32mmol), 2- dicyclohexylphosphino-2 ', 4', 6'-triisopropyl biphenyl (99mg, 0.207mmol) and tris (dibenzylideneacetone) palladium (0) (63.3mg, 0.069mmol) was then added to the mixture and the mixture was stirred for 5.5 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give compound c71 (0.75g, 74percent yield). [M + H] = 244.95, Method Condition 3: retention time 2.08 min
  • 2
  • [ 16066-84-5 ]
  • [ 851386-34-0 ]
  • C14H19FN2O3 [ No CAS ]
  • 3
  • [ 16066-84-5 ]
  • [ 1206972-45-3 ]
  • tert-butyl N-methyl-N-[5-(trifluoromethoxy)-2-pyridyl]carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In toluene; at 100 - 105℃; for 12h;Inert atmosphere; 24 g (120 mmol) of <strong>[1206972-45-3]2-chloro-5-(trifluoromethoxy)pyridine</strong>, 19.1 g (150 mmol) of tert-butyl N-methylcarbamate and 17.5 g (180 mmol) of sodium tert-butoxide were dissolved in 400 ml of toluene, 2.8 g (3 mmol) of tris(dibenzylideneacetone)dipalladium(0) and 1.73 g (3 mmol) of Xantphos were added under argon, and the mixture was stirred at 100-105 C. for 12 h. Subsequently, the mixture was filtered through Celite and the solvent was distilled off under reduced pressure.
  • 4
  • [ 16066-84-5 ]
  • [ 1206972-45-3 ]
  • tert-butyl N-methyl-N-[3-nitro-5-(trifluoromethoxy)-2-pyridyl]carbamate [ No CAS ]
 

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