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Chemical Structure| 15028-41-8 Chemical Structure| 15028-41-8

Structure of H-Aib-OMe.HCl
CAS No.: 15028-41-8

Chemical Structure| 15028-41-8

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Product Details of [ 15028-41-8 ]

CAS No. :15028-41-8
Formula : C5H12ClNO2
M.W : 153.61
SMILES Code : Cl.NC(C(=O)OC)(C)C
MDL No. :MFCD00214247
InChI Key :NVWZNEDLYYLQJC-UHFFFAOYSA-N
Pubchem ID :13258034

Safety of [ 15028-41-8 ]

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

Computational Chemistry of [ 15028-41-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 37.14
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.

0.0
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

0.6
Log Po/w (WLOGP)?

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

0.7
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

-0.38
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.26

Water Solubility

Log S (ESOL):?

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

-1.04
Solubility 14.1 mg/ml ; 0.0915 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.

-1.27
Solubility 8.2 mg/ml ; 0.0534 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

-0.37
Solubility 65.8 mg/ml ; 0.429 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.

-6.81 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)

1.0

Application In Synthesis of [ 15028-41-8 ]

* 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 [ 15028-41-8 ]

[ 15028-41-8 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 34404-33-6 ]
  • [ 15028-41-8 ]
  • [ 72086-77-2 ]
  • 2
  • [ 5545-54-0 ]
  • [ 15028-41-8 ]
  • [ 98607-20-6 ]
  • 3
  • [ 15028-41-8 ]
  • [ 426463-05-0 ]
  • [ 957194-63-7 ]
YieldReaction ConditionsOperation in experiment
78% With triethylamine; In ethanol; at 150℃; for 0.5h;Microwave irradiation; 2-(5-Iodo-3-nitro-pyridin-2-ylamino)-2-methyl-propionic acid methyl ester2-Chloro-5-iodo-3-nitro-pyridine (1.61 g) was dissolved in ethanol. Methyl a- aminoisobutyrate HCl was added (2.4 eq) followed by triethylamine (2.4 eq). The reaction mixture was heated to 1500C in a microwave oven for 30 minutes. The reaction mixture was concentrated to dryness and triturated with H2O. Silica gel chromatography of the resulting brown solid afforded the title compound as a bright yellow crystalline solid (78 % yield based on recovered starting material). M.p. 121-122 0C, 1H-NMR (CDCl3, 400 MHz) delta 1.56 (s, 3H), 1.66 (s, 3H), 3.67 (s, 3H), 8.53 (s, IH), 8.47 (d, J= 2.0 Hz, IH), 8.68 (d, J= 2.3 Hz, IH).
  • 4
  • [ 453562-71-5 ]
  • [ 15028-41-8 ]
  • [ 530-62-1 ]
  • [ 945103-85-5 ]
YieldReaction ConditionsOperation in experiment
Stage g: 3-(1-Acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-5,5-dimethylimidazolidine-2,4-dione A solution of 6.6 g of 1,1'-carbonylbis(1H-imidazole) and 460 mg of 1H-imidazole in 50 mL of tetrahydrofuran is stirred under argon and cooled in an ice bath at 0 C. To this solution is added a suspension of 6.9 g of <strong>[453562-71-5]1-acetyl-3,3-dimethylindolin-6-amine</strong> obtained in stage f) below in 50 mL of tetrahydrofuran. After stirring for one hour, 9.5 mL of triethylamine and 5.2 g of methyl 2-methylalaninate hydrochloride are added and the mixture is stirred for two hours at room temperature and then refluxed for 17 hours. After cooling to room temperature, the mixture is diluted with 800 mL of water and the precipitate formed is filtered off, washed with four times 25 mL of water and with three times 15 mL of diethyl ether and then dried to give 8 g of 3-(1-acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-5,5-dimethylimidazolidine-2,4-dione in the form of a beige-coloured solid, the characteristics of which are as follows: LCMS: RT=3.19 min; m/z=316 [M+H]+; m/z=314 [M-H]-
Steps A • and B:5,17 mmol ' of 1,1' -Carbonyldimidazole and 0,86- -mmo. ofimidazole are dissolved in 10 ml THF and cooled'to 0C. Asolution of 'the aromatic amine . (4,31 mmol ) in a .suitable'amount of THF' '(5 to 10 ml) is added over .15 mini..The.reaction mixture "is allowed to 'reach RT and stirred, f.oranother 2h. Then 4,3 'mmol of Net3 and 4,3 mmol .of ..2-'amino-2-methyl-propionic = acid methyl. ester ' .acid•hydrochlorid are added and ' the resulting mixture -,isstirred''until completion of the reaction. After theevaporation of the solvent ' the crude product is pure,enough • for ' the next step. Example 293- (l-Acetyl-3, 3-dimethyl-2, 3-dihydro-lH-indol-6-yl) -5, 5-• dimethyl-1- [2- (pyrazin-2- ylamino) -pyridin-4-ylmethyl] -• imi-dazoridine-2, 4-dione• Start-ing /from 1- (6^Amino-3, 3'-dimethyl-2, 3-dihydro-indol-1-yl) -ethanohe in step • A and' using steps,, B, C, D .arid* Ewith 2-aminopyrazine•M+H+ measured =• 50-0.24LC/MS retention time [min] =1.3.3- Example 7la ' .- . . , .3-(l-Acetyl-3,3-dimethyl-2,3-dihydro-lH-indol-6-yl)-5,5-dimethyl-imidazolidine-2,4- dione To a ' solution." of -838 mg d'i-imidazol-1-yl-methanone..and 58. mg imidazole in 10 ml • tetrahydrofuran a solution of 880 mg • 1-(6-amino-3f3-dimethyl-2,3-dihydro-indol-l-yl)-ethanone in 5 ml tetrahydrofuran was slowly added at 0C. After stirring at 0C for 90 minutes. 0.60 ml triethylamine and 661 mg 2-amino-2-methyl-propionic acid methyl- ester hydrochloride were added and the reaction mixture was allowed to warirv up to room temperature. After, 2 hours stirring at room temperature the solution was •heated for 6 hours at - 70C.' After cooling to ,room temperature'the solvent of the mixture was removed under reduced pressure and • the residue was purified by flash chromatography on silica gel with a n-heptane/ ethylacetate gradient. The fractions -containing the product were combined .and evaporated to yield a white solid.Yield: 920 mg'M+H-f- measured = 3161H-NMR (400 MHz, DMSO/TMS) : d = 8.50 (s, 1H) ; 7.93 (s, 1H);'7.33 (d, 1H) ; 6.97. - (dd, • 1H) ; 3.90 (s, 2H) ; 2.17 (s, 3H); 1.50 (s, 6H); 1.33 (s, 6H)
  • 5
  • [ 15028-41-8 ]
  • [ 146621-92-3 ]
  • [ 1366062-84-1 ]
YieldReaction ConditionsOperation in experiment
77% Example 18A Methyl N-[(tert-butoxycarbonyl)amino][3-(trifluoromethyl)phenyl]acetyl}-2-methylalaninate 450 mg (2.35 mmol) of EDC were added to a mixture of 500 mg (1.57 mmol) of [(tert-butoxycarbonyl)amino][3-(trifluoromethyl)phenyl]acetic acid and 317 mg (2.35 mmol) of HOBt in 10 ml of DMF, and the mixture was stirred at RT for 20 min. 313 mg (2.04 mmol) of methyl 2-methylalaninate hydrochloride and 382 mul (2.19 mmol) of N,N'-diisopropylethylamine were added and the mixture was stirrred overnight. For purification, the entire reaction mixture was separated by preparative HPLC [Method 6]. The appropriate fraction was concentrated on a rotary evaporator and the residue was dried under high vacuum. This gave 502 mg (77% of theory) of the title compound. LC-MS [Method 3]: Rt=1.28 min; MS [ESIpos]: m/z=319 (M+H-BOC)+; [ESIneg]: m/z=417 (M-H)-. 1H-NMR (400 MHz, DMSO-d6): delta [ppm]=1.26 (s, 3H), 1.38 (d, 12H), 3.44 (s, 3H), 5.31 (d, 1H), 7.45 (br. d, 1H), 7.56-7.62 (m, 1H), 7.63-7.71 (m, 2H), 7.75 (br. s, 1H), 8.61-8.69 (m, 1H).
  • 6
  • [ 66176-17-8 ]
  • [ 15028-41-8 ]
  • C13H18N2O3 [ No CAS ]
  • 7
  • [ 15028-41-8 ]
  • [ 171178-46-4 ]
  • methyl 2-(5-(tert-butoxycarbonylamino)-2-chloroisonicotinamido)-2-methylpropanoate [ No CAS ]
 

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