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Chemical Structure| 2491-20-5 Chemical Structure| 2491-20-5
Chemical Structure| 2491-20-5

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H-Ala-OMe·HCl

CAS No.: 2491-20-5

Synonyms: L-Alanine methyl ester (hydrochloride);Methyl L-Alaninate;L-Alanine methyl ester hydrochloride

4.5 *For research use only!

Cat. No.: A142845 Purity: 97%

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Product Details of [ 2491-20-5 ]

CAS No. :2491-20-5
Formula : C4H10ClNO2
Linear Structure Formula :[CH3O2CCH(CH3)NH3]Cl
M.W : 139.58
Synonyms :
L-Alanine methyl ester (hydrochloride);Methyl L-Alaninate;L-Alanine methyl ester hydrochloride
MDL No. :MFCD00063663
InChI Key :IYUKFAFDFHZKPI-DFWYDOINSA-N
Pubchem ID :2733257

Safety of [ 2491-20-5 ]

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

Calculated chemistry of [ 2491-20-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 0.75
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 32.3
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

0.41
Log Po/w (WLOGP)?

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

0.31
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.

0.01
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

-0.58
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.03

Water Solubility

Log S (ESOL):?

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

-0.83
Solubility 20.6 mg/ml ; 0.147 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.

-1.08
Solubility 11.7 mg/ml ; 0.0841 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

0.04
Solubility 153.0 mg/ml ; 1.1 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.

-6.86 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

2.0
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)

1.3

Application In Synthesis [ 2491-20-5 ]

* 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 [ 2491-20-5 ]

[ 2491-20-5 ] Synthesis Path-Downstream   1~24

  • 2
  • [ 108-86-1 ]
  • [ 2491-20-5 ]
  • [ 78603-91-5 ]
  • 3
  • [ 1142-20-7 ]
  • [ 2491-20-5 ]
  • [ 2483-51-4 ]
YieldReaction ConditionsOperation in experiment
90% With N-[2-(4-sulphonatephenylamino)-4-methoxy-1,3,5-triazin-6-yl]-4-methylmorpholinium inner salt; sodium hydrogencarbonate; In water; for 5h;Product distribution / selectivity; Example 19. A round-bottomed flask was charged with Z-Ala-OH (0.223 g, 0.001 mol), H-Ala-OMe x HCl (0.140 g, 0.001 mol), SPMT x 5H2O (0.471 g, 0.001 mol) and NaHCO3 (0.168 g, 0.002 mol). Water (10 ml) was added to the flask and the mixture was stirred using a magnetic stirrer. During the reaction, a formation of white precipitate was observed. After 5 hours, the precipitate was filtered off and dried in the air. Z-Ala-Ala-OMe (0.278 g, 90% yield) was obtained in the form of a white powder, having the m.p. of 93-94C (lit. 106-108C). The results of NMR analysis of the obtained compound are as follows: 1H NMR (acetone-d6) δ = 1.341 (d, J = 7 Hz, CH3, 3H); δ = 1.380 (d, J = 7 Hz, CH3, 3H); 3.673 (s, CH3, 3H); 4.240 (dp, J = 7.25 Hz, J = 2 Hz, CH, 1H); 4.435 (dp, J = 7.5 Hz, J = 1 Hz, CH, 1H); 5.077 (d, J = 1.5 Hz, CH2, 2H); 6.482 (m, NH, 1H); 7.267-7.417 (m, CArH, 5H); 7.536 (m, NH, 1H) [ppm].
52% With 4-methyl-morpholine; isobutyl chloroformate; In tetrahydrofuran; at 0 - 20℃; General procedure: To a solution of ((benzyloxy)carbonyl)-L-phenylalanine (0.72 g, 2.4 mmol, 1.0 eq) andN-methylmorpholine (0.97 g, 9.6 mmol, 4.0 eq) in anhydrous THF was added isobutylchloroformate (0.49 g, 3.6 mmol, 1.5 eq) at 0 C. The methyl L-alaninate hydrochloride(0.33 g, 2.4 mmol, 1.0 eq) was then added and the reaction was allowed to warm slowly toroom temperature overnight. The next day the reaction mixture was diluted with EtOAc(25 mL) and washed in succession with 1.0 M HCl (50 mL), 5% sodium carbonate solution(50 mL), brine (50 mL), then dried over sodium sulfate before filtering and concentrating invacuo. The residue was recrystallized in a DCM:Hexanes solution and filtered, yielding12g as a white crystalline solid (0.61 g, 1.6 mmol, 66%).
  • 4
  • [ 21947-97-7 ]
  • [ 2491-20-5 ]
  • [ 89028-36-4 ]
  • 5
  • [ 2491-20-5 ]
  • [ 26607-52-3 ]
  • [ 2483-51-4 ]
  • 6
  • [ 2491-20-5 ]
  • phenylmagnesium bromide [ No CAS ]
  • [ 78603-91-5 ]
  • 7
  • [ 2491-20-5 ]
  • Z-alanyl-p-toluenesulfonate [ No CAS ]
  • [ 2483-51-4 ]
  • 8
  • [ 2491-20-5 ]
  • [ 122751-37-5 ]
  • [ 2483-51-4 ]
  • 9
  • [ 5683-31-8 ]
  • [ 2491-20-5 ]
  • [ 80050-36-8 ]
  • 10
  • [ 100-59-4 ]
  • [ 2491-20-5 ]
  • [ 78603-91-5 ]
  • 11
  • [ 2491-20-5 ]
  • [ 53308-95-5 ]
  • (S)-2-((S)-2-tert-Butoxycarbonylamino-pentanoylamino)-propionic acid methyl ester [ No CAS ]
  • 12
  • [ 2491-20-5 ]
  • [ 51293-47-1 ]
  • (S)-2-((S)-2-tert-Butoxycarbonylamino-3-methoxy-propionylamino)-propionic acid methyl ester [ No CAS ]
  • 13
  • [ 51146-57-7 ]
  • [ 2491-20-5 ]
  • [ 354899-91-5 ]
  • 14
  • [ 96-81-1 ]
  • [ 2491-20-5 ]
  • N-acetyl-L-valinyl-L-alanine methyl ester [ No CAS ]
  • 15
  • [ 954147-36-5 ]
  • [ 2491-20-5 ]
  • Fmoc-Glu(tetrazole)-Ala-OMe [ No CAS ]
  • 16
  • [ 69651-48-5 ]
  • [ 2491-20-5 ]
  • [ 1004524-36-0 ]
YieldReaction ConditionsOperation in experiment
17.82 g With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; To a solution of 4-hydroxyphenylglycine (12 g, 71.860 mmol) in a 1:1 mixture of acetone and water was addeddi-tert-butyldicarbonate (16.5 mL, 71.8 mmol, 1 eq) andsodium bicarbonate (6.03 g, 0.11 mol, 1.5 eq). The solutionwas allowed to stir overnight, and then was quenched with theaddition of citric acid (pH 3) to pH 4. The aqueous layer was65 then extracted 2x with EtOAc and the combined organiclayers were washed with brine, dried over Na2S04 and concentratedto a white foam. The crude material (18.43 g, 69mmol (assumed)) was used without further purification bydissolving it in anhydrous DMF and treating sequentiallywith triethylamine (12.6 mL, 75.9 mmol, 1.3 eq), HOBT(9.32 g, 69 mmol, 1 eq) andAla-OMe HCl (9.63 g, 69 mmol,1 eq). The solution was then cooled to oo C. and EDC (19.55 5g, 0.1 mol, 1.5 eq) was added in one portion. The reaction wasallowed to warm to room temperature and stirred overnight.Water and EtOAc were added, the aqueous layer wasextracted 3x, and the combined organic layers were washedwith brine, dried over Na2S04 and concentrated. The residue 10was purified by flash chromatography (6% MeOH, 0.6%AcOH in DCM) to give a clear residue (17.82 g, 71% yield).Rf=0.39 (7% MeOH in DCM). 1H NMR (CDC13 , 600 MHz)o (ppm) 7.11 (d, 1=8.4 Hz, 2H), 6.64 (d, 1=8.4 Hz, 2H), 6.51 15(brd, 1=6.6 Hz, lH), 5.71 (brs, lH), 5.07 (brs, lH), 4.57-4.52(m, 1H),3.69(s,3H), 1.42-1.40(m, 12H). 13CNMR(CDC13 ,600 MHz) o (ppm) 173.2, 170.5, 156.6, 155.4, 129.0, 128.7(2C), 116.1 (2C), 80.5, 58.2, 52.7, 48.5, 28.4 (3C), 18.4. IR(film)vmax=1655, 1512,1450,1365,1215,1157,1049 cm-1. 20ESI HRMS calcd for [(M+NatJ C17H24N20 6 : 375.1526.found: 375.1532.
  • 17
  • [ 2491-20-5 ]
  • [ 37091-73-9 ]
  • [ 1032629-88-1 ]
  • 19
  • [ 2491-20-5 ]
  • [ 3543-75-7 ]
  • [ 1609623-17-7 ]
YieldReaction ConditionsOperation in experiment
63.3% With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 1.9 - 20℃; for 4h;Inert atmosphere; (S)-2-(4--{5-[Bis-(2-chloro-ethyl)-amino]-l-methyl-lH-benzoimidazol-2-yl}-butyrylam propionic acid methyl ester: A 250 mL three neck round bottom flask equipped with a stir bar, thermocouple, cooling bath, addition funnel and nitrogen in/outlet was charged with 10 g (25.3 mmol) of <strong>[3543-75-7]<strong>[3543-75-7]bendamustine</strong> hydrochloride</strong>, 10.6 g (27.8 mmol) of HATU and 100 mL of DMF. The batch was cooled to 1.9C where 8.8 mL (6.54 g, 50.6 mmol) of DIPEA was added over 2 minutes. The reaction exothermed to 9C and became orange. A solution of 3.57 g (25.6 mmol) of L-alanine methyl ester hydrochloride and 6.2 mL (4.57 g, 35.4 mmol) of DIPEA in 20 mL of DMF was added drop-wise over 10 minutes at 4.9-5.7C. The reaction was slowly warmed to RT over one hour and stirred for three hours at which time an in process assay indicated the reaction was complete. The batch was quenched onto 400 mL of 1 : 1 ethyl acetate/DI water. The layers were separated, the organic was washed with 10% sodium hydrogen phosphate (I X 200 mL), 8% sodium bicarbonate 91 X 200 mL) and brine (1 X 200 mL), before drying over sodium sulfate, filtering and evaporating to dryness in vacuo. The residue was purified by chromatography using lOOg of silica gel 60, 230-400 mesh, eluting with 1%> MeOH/MDC (3 L), 2.5 % MeOH/MDC (1L) and 5% MeOH/MDC (500 mL) collecting -100 mL fractions. The product containing fractions were combined and concentrated to dryness in vacuo to yield 7.1 g (16.0 mmol, 63.3%) of the desired product as a white solid with an HPLC purity of 97.4A%. XH NMR (400 MHz, DMSO-d6) delta 8.25 (d, J= 6.92 Hz), 1H), 7.40 (d, J= 8.84 Hz, 1H), 6.92 (d, J = 2.2 Hz, 1H), 6.86 (dd, J= 2.32, 8.88 Hz), 4.25 (q, 1H), 3.72 (s, 8H), 3.71 (s, 3H), 3.62 (s, 3H), 2.87 (t, J= 7.48 Hz, 2H), 2.25 (t, J= 7.52 Hz, 2H), 1.99 (m, 2H), 1.26 (d, J= 7.32 Hz, 3H).
  • 20
  • [ 2491-20-5 ]
  • [ 100-58-3 ]
  • [ 78603-91-5 ]
  • 21
  • [ 5545-54-0 ]
  • [ 2491-20-5 ]
  • (S)-methyl 2-((S)-2-(((benzyloxy)carbonyl)amino)-3-(4-(tert-butoxy)phenyl)propanamido)propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.3 g (S)-methyl 2-((S)-2-(((benzyloxy)carbonyl)amino)-3-(4-(tert-butoxy)phenyl)propanamido)propanoate To a solution of <strong>[5545-54-0](S)-2-(((benzyloxy)carbonyl)amino)-3-(4-(tert-butoxy)phenyl)propanoic acid</strong> (2.24 g, 6.03 mmol) and (S)-methyl 2-aminopropanoate hydrochloride (0.850 g, 6.09 mmol) in DCM (30.2 ml) at 0 C. was added solid HATU (2.408 g, 6.33 mmol). After 15 mins N-methylmorpholine (1.326 ml, 12.06 mmol) was added and the mixture was allowed to warm to RT, overnight. Added 1 N HCl 30 ml and extracted 3* with dichloromethane (30 mL), combined organics were dried over Na2SO4, filtered, and stripped to a wax. The residue was purified via normal phase chromatography, ISCO 80 grams silica, hexanes to ethyl acetate gradient, produced 1.3 grams. LCMS Condition E: retention time=0.97 mins 457.5 (M+1); 1H NMR (400 MHz, CHLOROFORM-d) delta 7.40-7.31 (m, 5H), 7.14-7.05 (m, J=8.1 Hz, 2H), 6.97-6.84 (m, 2H), 5.31 (s, 1H), 5.11 (s, 2H), 4.49 (s, 1H), 3.72 (s, 3H), 1.57 (br. s., 2H), 1.38-1.29 (m, 12H).
  • 22
  • [ 10601-99-7 ]
  • [ 2491-20-5 ]
  • C13H13NO3 [ No CAS ]
  • 23
  • [ 65638-93-9 ]
  • [ 2491-20-5 ]
  • [ 2483-51-4 ]
YieldReaction ConditionsOperation in experiment
General procedure: In a 3-neck round bottom flaskequipped with a septum, a thermometer and an adapter for a balloon with argon, Cbz-aminoacid(1.0 equiv., 5.0 mM) and N-ethylpiperidine (1.1 equiv., 5.5 mM) were dissolved in anhydrous methylenechloride (25 mL) and cooled to 10 C. Ethyl chloroformate (1.1 equiv., 5.5 mM) was added at the sametemperature, and the mixture protected from ingress of moisture was stirred for 2 h. Hydrochlorideof methyl L-alaninate or methyl glycinate (1.0 equiv., 5.0 mM) was dissolved in the second ask inanhydrous methylene chloride (10 mL) and cooled to 0 C, and then N-ethylpiperidine (1.0 equiv.,5.0 mM) was added. The whole volume of the second flask was immediately transferred to a 3-neckround bottom flask with the help of syringe, and additional N-ethylpiperidine (1.0 equiv., 5.0 mM)was added. The solution was stirred at the same temperature for 2 h and then left at 5 C overnight.After that, the reaction mixture was quenched with water (35 mL). The aqueous phase was extractedwith methylene chloride (3 15 mL). Combined organic phases were washed with 2M HCl solution(3 10 mL), water (10 mL), saturated sodium hydrogen carbonate solution (3 10 mL), and brine(10 mL) and dried over anhydrous sodium sulfate. After filtration, the solvent was removed underreduced pressure to give Cbz-amino dipeptide esters. The crude Cbz-amino dipeptide esters werehydrogenated with 60 mL of methanol and 10% Pd/C as a catalyst (0.5 g of Pd/C per 3 mM ofintermediate dipeptide esters) at room temperature. The reactor (250 mL capacity Parr reactor) waspressurized with hydrogen to 3 bars at ambient temperature. Reactor pressure remained unchangedduring the reaction period of 1 h. After releasing the pressure, the catalyst was removed by filtrationthrough Celite, and the solvent was removed under reduced pressure. The crude amino dipeptideesters were placed into a 250 mL round-bottomed flask equipped with an egg-shaped, Teflon-coated magnetic stirring bar and a reflux condenser, and toluene (100 mL) containing 5 mL of acetic acidwas added. The reaction mixture was stirred and refluxed for 2 h, then the reflux condenser wasremoved, and the amount of the solvent was reduced to 10% at atmospheric pressure. The remainingsolvent was removed under reduced pressure and the residue was recrystallized from propane-2-ol.Pure piperazine-2,5-diones 3-5 were dried at 40 C under reduced pressure.
  • 24
  • [ 2491-20-5 ]
  • [ 2848-01-3 ]
  • Ph<SUB>2</SUB>P-C<SUB>2</SUB>H<SUB>4</SUB>-CO-Ala-OMe [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% General procedure: The corresponding 4-(Diphenylphosphino)benzoic acid (1 mmol) was dissolved in dichloromethane (50 mL). HOBt*H2O (1 mmol), TBTU(1 mmol) and DIPEA (0.5 mL, 4 mmol) were added and the mixture was left stirring at room temperature. After 1 h methyl ester (1 mmol) was added and the mixture was left stirring for the indicated period. After that, the reaction mixture was washed with NaHCO3 (3×50 mL, sat.aq.) and subjected to flash chromatography (hexane/EtOAc).
 

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