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Chemical Structure| 84758-55-4 Chemical Structure| 84758-55-4

Structure of 84758-55-4

Chemical Structure| 84758-55-4

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Product Details of [ 84758-55-4 ]

CAS No. :84758-55-4
Formula : C10H19NO4
M.W : 217.26
SMILES Code : CC(C)(NC(OC(C)(C)C)=O)C(OC)=O
English Name :Methyl 2-((tert-butoxycarbonyl)amino)-2-methylpropanoate
MDL No. :MFCD20484740
InChI Key :OXGSYLWMSHXMLT-UHFFFAOYSA-N
Pubchem ID :15853247

Safety of [ 84758-55-4 ]

Computational Chemistry of [ 84758-55-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 6
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 56.02
TPSA ?

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

64.63 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.72
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

1.44
Log Po/w (WLOGP)?

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

1.46
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.

1.13
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

0.65
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.48

Water Solubility

Log S (ESOL):?

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

-1.7
Solubility 4.35 mg/ml ; 0.02 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.

-2.4
Solubility 0.86 mg/ml ; 0.00396 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

-1.74
Solubility 3.97 mg/ml ; 0.0183 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.

-6.6 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<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)

2.38

Application In Synthesis of [ 84758-55-4 ]

* 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 [ 84758-55-4 ]

[ 84758-55-4 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 84758-55-4 ]
  • [ 30992-29-1 ]
YieldReaction ConditionsOperation in experiment
99% Stage #1: N-(tert-butoxycarbonyl)-α-methylalanine methyl ester With lithium hydroxide In tetrahydrofuran; methanol; water at 20℃; for 12h; Stage #2: With hydrogenchloride In tetrahydrofuran; methanol; water 3.1 Preparation Example 1. Synthesis of 4-[2-(2-cyano-benzenesulfonylamino)-2-methyl-propionylamino]-adamantane-1-carboxylic acid amide (compound 130) In a 50-mL flask, methyl-2-aminobutoxycarbonyl-2-methylpropanoate (327 mg, 1.50 mmol) was charged, and dissolved through addition of tetrahydrofuran (15 ml), and methanol (15 ml). Lithium hydroxide dissolved in purified water (15 ml) was added thereto, followed by stirring for 12 hours at room temperature. After stirring for 12 hours, the resultant solution was vacuum-evaporated, neutralized with 2N-hydrochloric acid aqueous solution, and extracted with ethyl acetate (20mL). The organic layer was dried with magnesium sulfate, and filtered. Through vacuum distillation, the solvent was removed so as to obtain methyl-2-aminobutoxycarbonyl-2-methylpropanoic acid compound (335mg, 99 %).[615] 1H NMR (400 MHz, DMSO-d6) δ 12.1 (s, HO-CO-, 1H), 7.05 (s, -NH-CO2-, 1H), 1.40 (s, C3H9-O-, 9H), 1.25 (s, 6H).
99% With water; lithium hydroxide In tetrahydrofuran; methanol 3.1.335 In a 50-mL flask, methyl-2-aminobutoxycarbonyl-2-methylpropanoate (327 mg, 1.50 mmol) was charged, and dissolved through addition of tetrahydrofuran (15 ml), and methanol (15 ml). Lithium hydroxide dissolved in purified water (15 ml) was added thereto, followed by stirring for 12 hours at room temperature. After stirring for 12 hours, the resultant solution was vacuum-evaporated, neutralized with 2N-hydrochloric acid aqueous solution, and extracted with ethyl acetate (20 mL). The organic layer was dried with magnesium sulfate, and filtered. Through vacuum distillation, the solvent was removed so as to obtain methyl-2-aminobutoxycarbonyl-2-methylpropanoic acid compound (335 mg, 99%). [0336] 1H NMR (400 MHz, DMSO-d6) δ 12.1 (s, HO-CO-, 1H), 7.05 (s, -NH-CO2-, 1H), 1.40 (s, C3H9-O-, 9H), 1.25 (s, 6H).
40% With hydroxide
  • 2
  • [ 84758-55-4 ]
  • [ 102520-97-8 ]
YieldReaction ConditionsOperation in experiment
86.7% With lithium borohydride In ethanol
  • 3
  • [ 84758-55-4 ]
  • [ 184002-61-7 ]
YieldReaction ConditionsOperation in experiment
72% With hydrazine In methanol at 55℃; for 24h;
With hydrazine hydrate In isopropyl alcohol 17.2 Step 2: Step 2: tert-Butyl (2-hydrazino-1,1-dimethyl-2-oxoethyl)carbamate (P2) To a solution of P1 in 2-Propanol (0.56 M) was added hydrazine monohydrate (10 eq) and the mixture was stirred overnight at 90° C. Volatiles were removed under high vacuum and the obtained crude was used as such in the next step. MS (ES) C9H19N3O3 requires: 217, found: 240 (M+Na)+.
With hydrazine In isopropyl alcohol at 90℃; 17.2 Step 2: tert-Butyl (2-hydrazino-1,1-dimethyl-2-oxoethyl)carbamate (P2) To a solution of P1 in 2-Propanol (0.56 M) was added hydrazine monohydrate (10 eq) and the mixture was stirred overnight at 90° C. Volatiles were removed under high vacuum and the obtained crude was used as such in the next step. MS (ES) C9H19N3O3 requires: 217, found: 240 (M+Na)+.
  • 4
  • [ 30992-29-1 ]
  • [ 74-88-4 ]
  • [ 84758-55-4 ]
YieldReaction ConditionsOperation in experiment
96.6% With potassium hydrogencarbonate In N,N-dimethyl-formamide for 5h; Ambient temperature;
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 6h; 17.1 Step 1: Methyl N-(tert-butoxycarbonyl)-2-methylalaninate (P1) To a solution of Boc-α-methylalanine in DMF (0.4 M) was added K2CO3 (1 eq) and MeI (1.2 eq). The mixture was stirred at RT for 6 h and then diluted with EtOAc, washed with water and sat. aq. NaHCO3. The organic phase was dried over Na2SO4, filtered and concentrated under vacuum to provide the title compound as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ: 7.20 (1H, br. s), 3.58 (3H, s), 1.40-1.27 (15H, m). MS (ES) C10H19NO4 requires: 217, found: 240 (M+Na)+.
96 % With potassium carbonate In N,N-dimethyl-formamide at 20℃;
  • 5
  • [ 30992-29-1 ]
  • [ 77-78-1 ]
  • [ 84758-55-4 ]
YieldReaction ConditionsOperation in experiment
100% With lithium hydroxide In tetrahydrofuran for 2h; Heating;
  • 6
  • [ 67-56-1 ]
  • [ 30992-29-1 ]
  • [ 84758-55-4 ]
YieldReaction ConditionsOperation in experiment
94% With 4-methyl-morpholine; 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride
83.3% With sulfuric acid at 60℃; for 5h; 238.B methyl 2-(tert-butoxycarbonylamino)-2-methylpropanoate To a round bottom flask were added 2-(teri-butoxycarbonylamino)-2-methylpropanoic acid (2.0 g, 9.8 mmol), concentrated H2SO4 (0.1 mL), and MeOH (20 mL) and stirred at 60 °C for 5 h. The mixture was concentrated to dryness, the residue was diluted with EtOAc, washed with saturated NaHC03 and brine, dried over anhydrous Na2S04, filtered, and concentrated to dryness to give the title compound as a white solid 1.78 g, 83.3% yield).
83.3% With sulfuric acid at 60℃; for 5h; 238.B Step B: Methyl 2- (tert-butoxycarbonylamino) -2-methylpropanoate. To a round bottom flask were added 2- (tert-butoxycarbonylamino) -2-methylpropanoic acid (2.0 g, 9.8 mmol) , concentrated H2SO4(0.1 mL) , and MeOH (20 mL) and stirred at 60 for 5 h. The mixture was concentrated to dryness, the residue was diluted with EtOAc, washed with saturated NaHCO3and brine, dried over anhydrous Na2SO4, filtered, and concentrated to dryness to give the title compound as a white solid 1.78 g, 83.3yield) .
With dmap; Isopropenyl chloroformate; TEA In dichloromethane at 0 - 20℃;

  • 8
  • [ 84758-55-4 ]
  • [ 840506-46-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: TFA / CH2Cl2 / 2 h / 20 °C 2: TEA / CH2Cl2 / 2 h / -10 °C
  • 9
  • [ 84758-55-4 ]
  • [ 914911-59-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: TFA / CH2Cl2 / 2 h / 20 °C 2: TEA / CH2Cl2 / 2 h / -10 °C 3: 1-methylimidazole / CH2Cl2 / 20 h / 20 °C
  • 10
  • [ 84758-55-4 ]
  • [ 914911-27-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: TFA / CH2Cl2 / 2 h / 20 °C 2: TEA / CH2Cl2 / 2 h / -10 °C 3: 1-methylimidazole / CH2Cl2 / 20 h / 20 °C
  • 11
  • [ 84758-55-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 72 percent / N2H4 / methanol / 24 h / 55 °C 2: DMAP / tetrahydrofuran; hexane / 20 h 3: TBAF / tetrahydrofuran / 0.67 h / 22 °C
  • 12
  • [ 84758-55-4 ]
  • [ 184002-63-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 72 percent / N2H4 / methanol / 24 h / 55 °C 2: DMAP / tetrahydrofuran; hexane / 20 h
  • 13
  • [ 24424-99-5 ]
  • [ 84758-55-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 53.4 percent 2: 96.6 percent / potassium hydrogen carbonate / dimethylformamide / 5 h / Ambient temperature
Multi-step reaction with 2 steps 1: water; sodium hydroxide / tetrahydrofuran / 20 °C / Inert atmosphere 2: sulfuric acid / 5 h / 60 °C
Multi-step reaction with 2 steps 1: sodium hydroxide / water; tetrahydrofuran / 20 °C 2: sulfuric acid / 5 h / 60 °C
  • 14
  • [ 84758-55-4 ]
  • [ 107017-68-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 86.7 percent / lithium borohydride / ethanol 2: 85 percent / triethylamine / CH2Cl2 / 1 h / 0 °C
 

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