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Chemical Structure| 45214-91-3 Chemical Structure| 45214-91-3

Structure of Boc-Glu(OMe)-OH
CAS No.: 45214-91-3

Chemical Structure| 45214-91-3

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Synonyms: (S)-2-((tert-Butoxycarbonyl)amino)-5-methoxy-5-oxopentanoic acid

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Details of [ 45214-91-3 ]

CAS No. :45214-91-3
Formula : C11H19NO6
M.W : 261.27
SMILES Code : O=C(OC)CC[C@@H](C(O)=O)NC(OC(C)(C)C)=O
Synonyms :
(S)-2-((tert-Butoxycarbonyl)amino)-5-methoxy-5-oxopentanoic acid
English Name :(S)-2-((tert-Butoxycarbonyl)amino)-5-methoxy-5-oxopentanoic acid
MDL No. :MFCD00190794
InChI Key :OHYMUFVCRVPMEY-ZETCQYMHSA-N
Pubchem ID :7018756

Safety of [ 45214-91-3 ]

Computational Chemistry of [ 45214-91-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 0
Fraction Csp3 0.73
Num. rotatable bonds 9
Num. H-bond acceptors 6.0
Num. H-bond donors 2.0
Molar Refractivity 62.56
TPSA ?

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

101.93 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.88
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

0.74
Log Po/w (WLOGP)?

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

0.92
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.

0.52
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

0.29
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.87

Water Solubility

Log S (ESOL):?

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

-1.33
Solubility 12.2 mg/ml ; 0.0465 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.

-2.46
Solubility 0.907 mg/ml ; 0.00347 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

-1.14
Solubility 18.8 mg/ml ; 0.0719 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.

-7.37 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

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<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)

3.03

Application In Synthesis of [ 45214-91-3 ]

* 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 [ 45214-91-3 ]

[ 45214-91-3 ] Synthesis Path-Downstream   1~8

  • 2
  • [ 45214-91-3 ]
  • [ 125982-23-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: DCC / ethyl acetate / 1.) 0 deg C, 2.) 3 h, room temperature 2: NaBH4 / ethanol; tetrahydrofuran / 0.25 h / 0 °C 3: 92 percent / dl-10-camphorsulphonic acid (CSA) / benzene / 3 h / Heating
Multi-step reaction with 3 steps 1: DCC / ethyl acetate 2: NaBH4 / tetrahydrofuran; ethanol / 0.25 h / 0 °C 3: 92 percent / d,l-10-camphorsulfonic(CSA) / benzene / 3 h / 80 °C
Multi-step reaction with 2 steps 1.1: chloroformic acid ethyl ester; 4-methyl-morpholine / tetrahydrofuran / 0.33 h / 0 - 20 °C 1.2: 3 h / 0 - 20 °C 2.1: acetic acid / toluene / 1 h / Reflux
Multi-step reaction with 2 steps 1.1: 4-methyl-morpholine; isobutyl chloroformate / tetrahydrofuran / 0.33 h / 0 °C 1.2: 0 - 20 °C 2.1: acetic acid / toluene / 5 h / Reflux

  • 3
  • [ 45214-91-3 ]
  • [ 1563-56-0 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With dicyclohexyl-carbodiimide In dichloromethane at -10 - 0℃; for 41h; A1 Example A1 :Preparation of the compound of formula (B)222g (801 mmol) (2-amino-5-bromo-phenyl)-pyridin-2-yl-methanone of formula (A)(A) (prepared as described in European Journal of Organic Chemistry, 2006, 13, 2987- 2990) and 230g (881 mmol) 'Boc-Glu DMeJ-OH were mixed as solids and dissolved in 1200 ml dichloromethane and the solution was cooled to a temperature of - 10°C. A solution of coupling reagent dicyclohexylcarbodiimide DCC (165 g, 801 mmol) in 400 ml dichloromethane was added dropwise over a period of 1 hour while the internal temperature was kept at a temperature from - 10°C to - 5°C, then the solution was stirred for 40 hours at a temperature of - 5°C to 0 °C. The suspension was filtered, the filter cake was washed with 1000 ml dichloromethane and the filtrate was evaporated to a yellow residue, showing for the main product the following NMR data:1 H-NMR (CDCI3, 300 MHz) 11.29 (brs, 1 H); 8.65(dt, 1 H, J= 4.8, 1.4); 8.50 (d, 1 H, J= 9.0); 7.91(d, 1 H, J= 2.3); 7.86 (m, 2H); 7.59 (dd, 1 H, J= 9.0, 2.3) 7.45 (ddd, 1 H, J= 6.4, 4.0, 2.3); 5.27 (brd, 1 H, J=6.4); 4.27 (brm, 1 H); 3.60 (s, 3H); 2.52-2.14 (m, 2H); 2.04-1.82 (m, 2H); 1.36 (s, 9H), corresponding to the compound of formula (B).
  • 4
  • [ 45214-91-3 ]
  • [ 308242-23-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: dicyclohexyl-carbodiimide / dichloromethane / 41 h / -10 - 0 °C 2: hydrogenchloride / 1,4-dioxane; methanol / 3.25 h / 10 - 15 °C / Industry scale 3: sodium hydrogencarbonate / acetonitrile / 4.17 h / 15 - 20 °C / Industry scale
Multi-step reaction with 3 steps 1: dicyclohexyl-carbodiimide / dichloromethane / -10 - 0 °C 2: hydrogenchloride; methanol / 1,4-dioxane / 3.25 h / 10 - 20 °C 3: sodium hydrogencarbonate / 1,4-dioxane; acetonitrile; methanol / 15 - 20 °C
Multi-step reaction with 2 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; 4-methyl-morpholine / N,N-dimethyl-formamide / 0.5 h / Cooling with ice 2: trifluoroacetic acid / dichloromethane / Cooling with ice
  • 5
  • [ 45214-91-3 ]
  • [ 1563-56-0 ]
  • [ 1275616-57-3 ]
YieldReaction ConditionsOperation in experiment
With dicyclohexyl-carbodiimide In dichloromethane at -10 - 0℃; A.1 222g (801 mmol) (2-amino-5-bromo-phenyl)-pyridin-2-yl-methanone of formula (A) (prepared as described in European Journal of Organic Chemistry, 2006, 13, 2987-2990) and 230g (881 mmol)'Boc-Glu(OMe)-OH were mixed as solids and dissolved in 1200 ml dichloromethane and the solution was cooled to a temperature of - 10°C. A solution of coupling reagent dicyclohexylcarbodiimide DCC (165 g, 801 mmol) in 400 ml dichloromethane was added dropwise over a period of 1 hour while the internal temperature was kept at a temperature from - 10°C to - 5°C, then the solution was stirred for 40 hours at a temperature of - 5°C to 0 °C. The suspension was filtered, the filter cake was washed with 1000 ml dichloromethane and the filtrate was evaporated to a yellow residue, showing for the main product the following NMR data: 1H-NMR (CDCl3, 300 MHz) 11.29 (brs, 1H); 8.65(dt, 1H, J= 4.8, 1.4); 8.50 (d. 1H, J= 9.0); 7.91 (d, 1H, J= 2.3); 7.86 (m, 2H); 7.59 (dd, 1H, J= 9.0, 2.3) 7.45 (ddd, 1H. J= 6.4, 4.0, 2.3); 5.27 (brd, 1H. J=6.4); 4.27 (brm, 1H): 3.60 (s, 3H); 2.52-2.14 (m, 2H); 2.04-1.82 (m, 2H); 1.36 (s, 9H), corresponding to the compound of formula (B).
  • 6
  • [ 45214-91-3 ]
  • [ 1990504-72-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: pivaloyl chloride; 4-methyl-morpholine / Isopropyl acetate / 2 h / -5 - 5 °C / Inert atmosphere; Large scale 1.2: 1 h / -5 - 5 °C / Inert atmosphere; Large scale 2.1: hydrogenchloride / 1,4-dioxane; sulfolane / 4.5 h / 25 - 30 °C 3.1: 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 1.5 h / 20 - 25 °C / Inert atmosphere 4.1: potassium trimethylsilonate / tetrahydrofuran / 14 h / 25 - 30 °C / Inert atmosphere 5.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 15 h / 0 - 20 °C / Inert atmosphere; Large scale 6.1: 2.5 wt% Pd/C; triethylsilane; acetic acid / tetrahydrofuran / 7 h / 5 - 20 °C / Inert atmosphere 7.1: methanol; tetrahydrofuran / 2 h / -15 - -5 °C 7.2: 1 h / 15 - 25 °C 8.1: isopropyl alcohol; tetrahydrofuran / 15 h / 20 - 30 °C / Large scale
Multi-step reaction with 9 steps 1.1: pivaloyl chloride; 4-methyl-morpholine / Isopropyl acetate / 2 h / -5 - 5 °C / Inert atmosphere; Large scale 1.2: 1 h / -5 - 5 °C / Inert atmosphere; Large scale 2.1: hydrogenchloride / 1,4-dioxane; sulfolane / 4.5 h / 25 - 30 °C 3.1: 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 1.5 h / 20 - 25 °C / Inert atmosphere 4.1: potassium trimethylsilonate / tetrahydrofuran / 14 h / 25 - 30 °C / Inert atmosphere 5.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 15 h / 0 - 20 °C / Inert atmosphere 5.2: 20 - 30 °C 6.1: sodium carbonate / tert-butyl methyl ether; water / 4 h / 15 - 25 °C / Large scale 7.1: 2.5 wt% Pd/C; triethylsilane; acetic acid / tetrahydrofuran / 7 h / 5 - 20 °C / Inert atmosphere 8.1: methanol; tetrahydrofuran / 2 h / -15 - -5 °C 8.2: 1 h / 15 - 25 °C 9.1: isopropyl alcohol; tetrahydrofuran / 15 h / 20 - 30 °C / Large scale
  • 7
  • [ 45214-91-3 ]
  • [ 1830-42-8 ]
  • [ 2101840-46-2 ]
YieldReaction ConditionsOperation in experiment
67.3% With dicyclohexyl-carbodiimide In dichloromethane at 0℃; for 24h; 20.3 Step 3. Preparation of (S)-methyl 5-((4-chloro-2-picolinoylphenyl)amino)-4-((tert-butoxycarbonyl)amino)-5-oxopentanoate (Compound 20c) (2-Amino-5-chlorophenyl)(pyridin-2-yl)methanone (compound 20b, 4 g, 17.2 mmol) and 5-methyl N-tert-butoxycarbonyl-L-glutamate (6.7 g, 25.8 mmol) were dissolved in DCM (50 mL). The mixture was cooled to 0° C., and DCC (7.1 g, 34.4 mmol was added). The mixture was stirred for 24 h until LCMS indicated that the reaction was completed. The reaction mixture was poured into ice water, and extracted with ethyl acetate. The organic layer was washed with water for three times, dried and concentrated. The residue was purified through silica gel column chromatography to obtain (S)-methyl 5-((4-chloro-2-picolinoylphenyl)amino)-4-((tert-butoxycarbonyl)amino)-5-oxopentanoate (compound 20c, 5.5 g, yield 67.3%).
  • 8
  • [ 45214-91-3 ]
  • [ 1563-56-0 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
69% Stage #1: (2S)-2-[(tert-butoxy)carbonylamino]-4-(methoxycarbonyl)butanoic acid With 4-methyl-morpholine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide for 0.5h; Cooling with ice; Stage #2: 2-amino-5-bromobenzoyl pyridine In N,N-dimethyl-formamide 2.1 Step 1. Preparation of (S)-methyl 5-((4-bromo-2-nicotinoylphenyl)amino)-4-((tert-butoxycarbonyl)amino)-5-ozopentanoate (Compound 2b) HATU (45.6 g, 0.12 mol), N-methylmorpholine (20.2 g, 0.2 mol) and 5-methyl N-Boc-L-glutamate (16.1 g, 0.1 mol) were sequentially added to DMF (100 mL) in an ice bath. The resulted mixture was allowed to react for 30 min in an ice bath, and then (2-amino-5-bromophenyl)(pyridin-2-yl)methanone (compound 2a, 27.7 g, 0.1 mol) was added. Water was added to the reaction system after TLC indicated that the reaction was completed, and the mixture was extracted with ethyl acetate (20 mL*4). The ethyl acetate layer was evaporated to dry, and the residue was purified through silica gel column chromatography to obtain (S)-methyl 5-((4-bromo-2-nicotinoylphenyl)amino)-4-((tert-butoxycarbonyl)amino)-5-oxopentanoate (compound 2b, 36 g, yield: 69%).
 

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