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Chemical Structure| 6456-74-2 Chemical Structure| 6456-74-2

Structure of tert-Butyl Glycinate
CAS No.: 6456-74-2

Chemical Structure| 6456-74-2

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Synonyms: tert-Butyl 2-aminoacetate

4.5 *For Research Use Only !

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Product Details of [ 6456-74-2 ]

CAS No. :6456-74-2
Formula : C6H13NO2
M.W : 131.17
SMILES Code : CC(C)(C)OC(=O)CN
Synonyms :
tert-Butyl 2-aminoacetate
MDL No. :MFCD00038194
InChI Key :SJMDMGHPMLKLHQ-UHFFFAOYSA-N
Pubchem ID :151417

Safety of [ 6456-74-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 6456-74-2 ] 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 3.0
Num. H-bond donors 1.0
Molar Refractivity 34.99
TPSA ?

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

52.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.68
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

0.19
Log Po/w (WLOGP)?

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

0.29
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.

0.39
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

0.01
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.51

Water Solubility

Log S (ESOL):?

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

-0.57
Solubility 34.9 mg/ml ; 0.266 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.

-0.85
Solubility 18.7 mg/ml ; 0.142 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

-0.79
Solubility 21.3 mg/ml ; 0.163 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.

-6.97 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)

1.03

Application In Synthesis of [ 6456-74-2 ]

* 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 [ 6456-74-2 ]

[ 6456-74-2 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 6456-74-2 ]
  • [ 17823-69-7 ]
  • [ 118534-48-8 ]
  • 2
  • [ 6456-74-2 ]
  • [ 132874-06-7 ]
  • [ 681430-73-9 ]
  • 3
  • [ 6456-74-2 ]
  • [ 37091-73-9 ]
  • 2-(tert-butyloxycarbonylmethylimino)-1,3-dimethylimidazolidine [ No CAS ]
  • 4
  • [ 6456-74-2 ]
  • [ 50595-15-8 ]
  • 5
  • [ 6456-74-2 ]
  • [ 42017-89-0 ]
  • [ 1094101-23-1 ]
YieldReaction ConditionsOperation in experiment
79% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; Coupling of fenofbric acid (1) with EDC / HOBT in Dichloromethane followed by t-butylglycine gave t-butyl protected 118 in 79% yield after chromatography (ethyl acetate/hexane) 1H-NMR (CDCl3): delta 7.74 (d, 2H, J= 9 Hz), 7.72 (d, 2H, J= 9 Hz), 7.53 (d, 2H, J= 8 Hz), 7.10 (d, 2H, J= 8 Hz), 3.83 (s, 2H), 1.60 (s, 6H), 1.45 (s, 9H) ppm.
  • 6
  • [ 6456-74-2 ]
  • [ 68858-20-8 ]
  • [ 198561-07-8 ]
  • [ 1134204-67-3 ]
  • 7
  • [ 6456-74-2 ]
  • [ 21080-80-8 ]
  • [ 1263082-20-7 ]
YieldReaction ConditionsOperation in experiment
With toluene-4-sulfonic acid; In toluene; at 130℃; for 4h; To a solution of a compound 1 (262 mg, 2.0 mmol) in toluene (5 mL) were added a compound II (368 mg, 2.0 mmol) and p-toluenesulfonic acid monohydrate (19 mg, 0.1 mmol), and the resulting solution was stirred at 130 °C for 4 hours. The reaction mixture was poured into saturated sodium bicarbonate aqueous solution and extracted with ethyl acetate, then the organic layer was washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, concentrated in vacuo to give a compound III (281 mg, Yield 47percent) as yellow oil. The obtained compound III was used for the next reaction without further purification. 1 H NMR (DMSO-d6) delta: 0.78-0.84 (m, 4H), 1.24-1.28 (m, 3H), 1.40 (s, 9H), 1.90-2.00 (m, 1H), 4.10-4.25 (m ,4.H), 5.78 (d, J = 1.2 Hz, 1H), 10.01 (brs, 1H).
  • 8
  • [ 5683-31-8 ]
  • [ 6456-74-2 ]
  • tert-butyl 2-(3-(trimethylsilyl)propiolamido)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% Isobutyl chloroformate (357.2 mg, 2.6 mmol) was dropwise added to a solution of <strong>[5683-31-8]3-(trimethylsilyl)propiolic acid</strong> 25 (372 mg, 2.6 mmol) and NMM (344 mg, 3.4 mmol) in THF (10 mL) at -40 oC. The reaction was stirred at -40 to -10 oC for 40 min. A solution of tert-butyl 2-aminoacetate 26 (447 mg, 3.4 mmol) and NMM (344 mg, 3.4 mmol) in co-solvents THF/DMF (5 mL/1 mL) was slowly added to the reaction solution at -40 oC for 20 min. The mixture slowly recovered to r.t. from -40oC and was stirred overnight at r.t.. After concentration, the residue was dissolved in CH2Cl2, washed by NaHCO3 and brine, dried by Na2SO4 and purified by silica gel column chromatography (5-10% EtOAc/Hexanes, stepwise gradient by 5%, then 10% iPrOH /Hexanes) to afford 27. Yield: 428 mg, 64%. 1H NMR (CDCl3, 600 MHz) 6.41 (b, 1H), 3.97 (d, J = 5.4 Hz, 1H), 1.49 (s, 9H), 0.23 (s, 9H). MS (ESI) [M+H]+ 256.4, found 256.0.
  • 9
  • [ 201230-82-2 ]
  • [ 6456-74-2 ]
  • [ 131818-17-2 ]
  • [ 1597414-90-8 ]
  • 10
  • [ 6456-74-2 ]
  • [ 1641-69-6 ]
  • [ 131818-17-2 ]
  • [ 1622398-91-7 ]
  • 11
  • [ 6456-74-2 ]
  • [ 122889-11-6 ]
  • [ 675882-22-1 ]
YieldReaction ConditionsOperation in experiment
85% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; Amino acid S30 (27 mg, 0.065 mmol) and S31 (10 mg, 0.0599 mmol) were dissolved in 0.6 mL dry DMF, followed by addition of HATU (30mg, 0.077mmol), DIPEA (25|xL 0.1797 mmol). The resulting mixture was stirred under room temperature overnight and diluted with EtOAc. The solution was washed with 1M HCl and a saturated aqueous NaHCO3 solution. The combined organic phase was dried over Na2SO4 and concentrated, purified by silica gel column to afford compound S32 (27 mg, 85percent).
  • 12
  • [ 1122-12-9 ]
  • [ 6456-74-2 ]
  • (3,4-dibromo-2,5-dioxo-2,5-dihydro-pyrrol-1-yl)acetic acid tert-butyl ester [ No CAS ]
  • 13
  • [ 2483-51-4 ]
  • [ 6456-74-2 ]
  • [ 35766-23-5 ]
YieldReaction ConditionsOperation in experiment
48% With 2,2':6',2'':6'',2'''-quaterpyridine; pentamethoxy tantalum; at 70℃; for 48h; Amide compounds were produced by reacting an aminoester compound with an amino compound under the respective reaction conditions below in the presence of a Ta(OMe)5 catalyst and a ligand. The yield for each product is indicated below the formula. In the reaction formula below, L-ala represents an L-alanine residue, Val represents an L-valine residue, Leu represents an L-Leucine residue, ILe represents an L-isoleucine residue, Gly represents glycine residue, Phe represents an L-phenylalanine residue, and Thr(OtBu) represents O-(tert butyl) L-threonine residue.
 

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