[ CAS No. 4125-93-3 ] {[proInfo.proName]}

Name: 4125-93-3|H-Asp-OtBu|98% HPLC
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SKU: A330682
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Quality Control of [ 4125-93-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 4125-93-3 ]

SDS Specification

Alternatived Products of [ 4125-93-3 ]

Product Details of [ 4125-93-3 ]

CAS No. :	4125-93-3	MDL No. :	MFCD00171675
Formula :	C₈H₁₅NO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PUWCNJZIFKBDJQ-YFKPBYRVSA-N
M.W :	189.21	Pubchem ID :	7016377
Synonyms :

Calculated chemistry of [ 4125-93-3 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.75
Num. rotatable bonds :	5
Num. H-bond acceptors :	5.0
Num. H-bond donors :	2.0
Molar Refractivity :	46.37
TPSA :	89.62 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-9.27 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.24
Log Po/w (XLOGP3) :	-2.56
Log Po/w (WLOGP) :	0.13
Log Po/w (MLOGP) :	0.1
Log Po/w (SILICOS-IT) :	-0.23
Consensus Log Po/w :	-0.27

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	0.93
Solubility :	1610.0 mg/ml ; 8.51 mol/l
Class :	Highly soluble
Log S (Ali) :	1.22
Solubility :	3160.0 mg/ml ; 16.7 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	-0.25
Solubility :	106.0 mg/ml ; 0.562 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.46

Safety of [ 4125-93-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 4125-93-3 ]

* 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.

Upstream synthesis route of [ 4125-93-3 ]
Downstream synthetic route of [ 4125-93-3 ]

[ 4125-93-3 ] Synthesis Path-Upstream 1~3

1
[ 129460-09-9 ]
[ 4125-93-3 ]

Reference： [1] Patent: US2007/72800, 2007, A1, . Location in patent: Page/Page column 13

2
[ 540-88-5 ]
[ 56-84-8 ]
[ 4125-93-3 ]

Reference： [1] Patent: CN106045883, 2016, A, . Location in patent: Paragraph 0060-0062

3
[ 94347-11-2 ]
[ 4125-93-3 ]

Reference： [1] Journal of Organic Chemistry, 1963, vol. 28, p. 1251 - 1253

[ 4125-93-3 ] Synthesis Path-Downstream 1~37

1
[ 94347-11-2 ]
[ 4125-93-3 ]

Reference： [1]Journal of Organic Chemistry,1963,vol. 28,p. 1251 - 1253

2
[ 75-77-4 ]
[ 4125-93-3 ]
N-(Trimethylsilyl)asparaginsaeure-1-tert-butylester [ No CAS ]

Reference： [1]Liebigs Annalen der Chemie,1983,vol. No. 3,p. 337 - 359

3
[ 4125-93-3 ]
[ 129943-30-2 ]
[ 129943-33-5 ]

Reference： [1]Angewandte Chemie,1990,vol. 102,p. 1520 - 1522

4
[ 4125-93-3 ]
[ 116864-60-9 ]
[ 116864-67-6 ]

Reference： [1]Angewandte Chemie,1988,vol. 100,p. 1424 - 1425

5
[ 4125-93-3 ]
[ 557095-50-8 ]
Fmoc-Val-Asp-OtBu [ No CAS ]

Reference： [1]Tetrahedron Letters,2003,vol. 44,p. 3187 - 3190

6
[ 4125-93-3 ]
[ 501-53-1 ]
[ 47307-26-6 ]

Yield	Reaction Conditions	Operation in experiment
97%		The protection of the amine of this compound is then carried out in the following way:Sodium bicarbonate (13 g, 159 mmol) and, over the course of a period of 2 hours, a solution of benzyl chloroformate (11.8 mL, 69 mmol) in dioxane (70 mL) are added to a solution of alpha-tert-butyl aspartate (10 g, 53 mmol) in a water/dioxane mixture (2/1) (170 mL). Stirring is carried out overnight at ambient temperature. The reaction medium is washed with ethyl acetate (3×200 mL), and then acidified at 0 C. with a 6N hydrochloric acid solution until pH=2. The aqueous phase is extracted with ethyl acetate (3×200 mL). The combined organic phases are washed with brine (200 mL) and then dried over anhydrous magnesium sulfate and concentrated so as to obtain the compound 2 in the form of a colorless oil (16.7 g, 97.96).The compound 2 having the following formula is obtained: Rf: (CHCl3/MeOH/AcOH 37%)=0.68HPLC: 1.56 minMS: [M+H]+, 324.1; [M+H-tBu]+, 268.11H NMR (CDCl3, 300 MHz): 1.45 (s, 9H, 1 tBu); 2.95 (dd, 2H, J=4.5 and 14 Hz, CH2beta); 4.55 (q, 1H, J=4.3 Hz, CHalpha); 5.10 (s, 2H, CH2Ph); 5.8 (d, 1H, J=8 Hz, NH); 7.35 (m, 5H, arom); 10.7 (bs, 1H, COOH)13C NMR (CDCl3, 75 MHz): 27.79; 36.73; 50.75; 67.12; 82.83; 128.11; 128.20; 128.53; 136.12; 156.06; 169.46; 176.25.
50%	With sodium hydroxide; In 1,4-dioxane; water; at 0 - 20℃;	Stage 1; - (3S)-3-[(Benzyloxy)carbonyl]amino}-4-fert-butoxy-4-oxobutanoic acid; To a solution of (3S)-3-amino-4-te/t-butoxy-4-oxobutanoic acid (900mg, 4.75mmol) and sodium hydroxide (280mg, 7.13mmol) in 25% water/dioxane (5OmL) at 00C was added benzyl chloroformate (2g, 4.13mmol) in dioxane (1 OmL). The mixture was stirred at O0C for 1 hour and then at RT overnight. Water (1 OmL) was added and the mixture was extracted with EtOAc (2 x 2OmL). The organic phase was back extracted with a saturated aqueous solution of NaHCO3 (2 x 1 OmL). The combined aqueous layers were EPO <DP n="28"/>acidified to pH 1 with 1 M HCI, and extracted with EtOAc (3 x 1OmL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The residue was purified by column chromatography (35% EtOAc/heptane) to give the product as a colourless oil (0.76g, 50% yield). ESMS: m/z 346 [M+23] +
50%	With sodium hydroxide; In 1,4-dioxane; water; at 0 - 20℃;	Intermediate2: terf-butyl (2S)-2-U(benzyloxy)carbonvnamino)-4-bromobutanoateThe title intermediate was prepared according to the procedure outlined below in Scheme 10.Stage 1Stage 2Stage 3Scheme 10Stage 1- (3S)-3-[(Benzyloxy)carbonyl]amino}-4-tert-butoxy-4-oxobutanoic acidTo a solution of (3S)-3-amino-4-ferf-butoxy-4-oxobutanoic acid (900 mg, 4.75 mmol) and sodium hydroxide (280 mg, 7.13 mmol) in 25% water/dioxane (50 mL) at 0 0C was EPO <DP n="33"/>added benzyl chloroformate (2 g, 4.13 mmol) in dioxane (10 mL). The mixture was stirred at O0C for 1 hour and then at RT overnight. Water (10 mL) was added and the mixture was extracted with EtOAc (2 x 20 mL). The organic phase was back extracted with a saturated aqueous solution of NaHCO3 (2 x 10 mL). The combined aqueous layers were acidified to pH 1 with 1M HCI, and extracted with EtOAc (3 x 10 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The residue was purified by column chromatography (35% EtOAc/heptane) to give the product as a colourless oil (0.76 g, 50% yield). ESMS: m/z 346 [M+23] +

With sodium carbonate; In 1,4-dioxane; water; at 20℃;

The (2S)-2-[(benzyloxy)carbonyl]amino}succinic acid used in the above procedure was prepared as follows:To a solution of (S)-aspartic acid t-butyl ester (5,Og, 26mmol) in water-dioxane (100ml, 1 :1 v/v) was added Na2CO3 (14.Og, 132mmol) slowly, followed by benzyl chloroformate (4.15ml, 29mmol) and the resulting mixture stirred overnight at room temperature. The reaction was then diluted with ethyl acetate (50ml) and acidified to pH2 with concentrated HCI. The aqueous layer was separated and extracted with ethyl acetate (2x50ml). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated under reduced pressure to give the desired product (8.54g) as a colourless oil which was used without purification, m/z 346 [M+Na]+.

Reference： [1]European Journal of Organic Chemistry,2009,p. 2729 - 2732
[2]European Journal of Organic Chemistry,2010,p. 6609 - 6617
[3]Chemical Communications,2011,vol. 47,p. 5825 - 5827
[4]Patent: US2012/95262,2012,A1 .Location in patent: Page/Page column 2
[5]Patent: WO2008/50096,2008,A1 .Location in patent: Page/Page column 26-27
[6]Patent: WO2008/53157,2008,A1 .Location in patent: Page/Page column 31-32
[7]Patent: WO2007/129036,2007,A1 .Location in patent: Page/Page column 29

7
[ 4125-93-3 ]
[ 86088-19-9 ]

Reference： [1]Liebigs Annalen der Chemie,1983,vol. No. 3,p. 337 - 359

8
[ 4125-93-3 ]
[ 31139-36-3 ]
[ 47307-26-6 ]

Yield	Reaction Conditions	Operation in experiment
50%	With sodium hydroxide; In 1,4-dioxane; water; at 0 - 20℃;	(S)~2-Amino-succinic acid 1-tert-butyl ester (0.9g, 4.75mmol) and sodium hydroxide (0.28g, 7.13mmol, 1.5eq) were dissolved in 25% water in dioxane (50ml). The solution was stirred at 50C and dibenzyldicarbonate (2g, 4.13mmol, 1.5eq) in dioxane (10ml) was added slowly. The mixture was stirred at O0C for 1 h and then at r. t. overnight. Water (10ml) was added and the mixture was extracted with EtOAc (2 x 20ml). The organic phase was back extracted with a sat. aq. Solution of sodium bicarbonate (2 x 10ml). The combined aq. Layers were acidified to pH 1 with 1M HCI, and extracted with EtOAc (3 x 10ml). The combined organic fractions were dried over MgSO4 and concentrated under reduced pressure. The product was purified by column chromatography (35% EtOAc in heptane) to afford the title compound as a colorless oil (0.76g, 50%). m/z 346 [M+23] +, 1H NMR (300 MHz, CDCI3), delta: 7.39-7.32 (5H, m), 5.72 (1H, d, J = 8.1Hz), 5.13 (2H, s), 4.58-4.50 (1H, m), 3.10-2.99 (1 H, m), 2.94-2.83 91 H, m), 1.45 (9H, s).
50%	With sodium hydroxide; In 1,4-dioxane; water; at 0 - 20℃;	(S)-2-Amino-succinic acid 1-tert-butyl ester (0.9 g, 4.75 mmol) and sodium hydroxide (0,28 g, 7.13 mmol, 1.5 eq) were dissolved in 25% water in dioxane (50 ml). The solution was stirred at 50C and dibenzyldicarbonate (2 g, 4.13 mmol, 1.5 eq) in dioxane (10 ml) was added slowly. The mixture was stirred at O0C for 1 hour and then at room temperature overnight. Water (10 ml) was added and the mixture was extracted with ethyl acetate (2 x 20 ml). The organic phase was back extracted with a saturated aqueous solution of sodium bicarbonate (2 x 10 ml). The combined aqueous layers were acidified to pH 1 with 1M HCI, and extracted with ethyl acetate (3 x 10 ml). The combined organic fractions were dried over magnesium sulphate and concentrated under reduced pressure. The product was purified by column chromatography (35% ethyl acetate in heptane) to provide 0.76 g (50% yield) of title compound as a colourless oil.LC/MS: m/z 346 [M+23] +, 1H NMR (300 MHz, CDCI3), delta 7.39-7.32 (5H, m), 5.72 (1 H, d, J=8.1 Hz), 5.13 (2H, s), 4.58-4.50 (1H, m), 3.10-2.99 (1 H, m), 2.94-2.83 (1 H, m), 1.45 (9H, s).

Reference： [1]Patent: WO2006/117567,2006,A2 .Location in patent: Page/Page column 45
[2]Patent: WO2006/117552,2006,A1 .Location in patent: Page/Page column 101-103

9
[ 112-16-3 ]
[ 4125-93-3 ]
lauroyl-Asp-OBut [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 20℃; for 3.5h;Phosphate buffer;	One mmol of Fmoc-Asp-OBut was incubated in 20% piperidine in DMF for 20 minutes. 10-fold volume of diethyl ether was added to the solution. The mixture was cooled and the precipitate of H-Asp-OBut was centrifuged. The precipitate was washed with diethyl ether 3 times. 1.1 mmol of lauroyl chloride was slowly added to the mixture of 1 mmol of H-Asp-OBut and 10 ml phosphate buffer pH 9 for 30 minutes at room temperature, and allowed to shake for another 3 hours. 1N HCl was added drop-wise to pH 6. The precipitate of Lauroyl-Asp-OBut was filtered and washed with water and toluene. 1 mmol of Lauroyl-Asp-OBut was dissolved in 20 ml DCM. The mixture was cooled to 0 C. 1.1 mmol of DCC was dissolved in 10 ml DCM and added to the Lauroyl-Asp-OBut mixture. The reaction was carried out for 30 minutes on cold ice and continued for another 2 hours at room temperature. The white crystals appeared in the mixture were filtered out. 1 mmol of solid 2,4-dioxo-5-fluoropyrimidine was added to the clear solution of activated Lauroyl-Asp-OBut. The reaction was carried out for 20 hours in room temperature. The mixture was filtered and the DCM was evaporated. The product (Lauroyl-Asp(5FU)-OBut) was washed several times with water and ethanol and air-dried. Cleavage of the protecting group (OtBu) was carried out in lml TFA (trifluoroacetic acid)+5% water for 3 hours. The acid was evaporated in a vacuum over KOH pellet. The final product was washed several times with diethyl ether and dried. N-alpha-Lauroyl-L-aspartic acid beta-1N-(2,4-dioxo-5-fluoropyrimidine) was recrystallized from methanol+Hexane. Yield of the product was 70% of white crystals. Molecular weight 427 g/mol.

Reference： [1]Patent: US2007/72800,2007,A1 .Location in patent: Page/Page column 13

10
[ 129460-09-9 ]
[ 4125-93-3 ]

Yield	Reaction Conditions	Operation in experiment
	With piperidine; In N,N-dimethyl-formamide; for 0.333333h;	One mmol of Fmoc-Asp-OBut was incubated in 20% piperidine in DMF for 20 minutes. 10-fold volume of diethyl ether was added to the solution. The mixture was cooled and the precipitate of H-Asp-OBut was centrifuged. The precipitate was washed with diethyl ether 3 times. 1.1 mmol of lauroyl chloride was slowly added to the mixture of 1 mmol of H-Asp-OBut and 10 ml phosphate buffer pH 9 for 30 minutes at room temperature, and allowed to shake for another 3 hours. 1N HCl was added drop-wise to pH 6. The precipitate of Lauroyl-Asp-OBut was filtered and washed with water and toluene. 1 mmol of Lauroyl-Asp-OBut was dissolved in 20 ml DCM. The mixture was cooled to 0 C. 1.1 mmol of DCC was dissolved in 10 ml DCM and added to the Lauroyl-Asp-OBut mixture. The reaction was carried out for 30 minutes on cold ice and continued for another 2 hours at room temperature. The white crystals appeared in the mixture were filtered out. 1 mmol of solid 2,4-dioxo-5-fluoropyrimidine was added to the clear solution of activated Lauroyl-Asp-OBut. The reaction was carried out for 20 hours in room temperature. The mixture was filtered and the DCM was evaporated. The product (Lauroyl-Asp(5FU)-OBut) was washed several times with water and ethanol and air-dried. Cleavage of the protecting group (OtBu) was carried out in lml TFA (trifluoroacetic acid)+5% water for 3 hours. The acid was evaporated in a vacuum over KOH pellet. The final product was washed several times with diethyl ether and dried. N-alpha-Lauroyl-L-aspartic acid beta-1N-(2,4-dioxo-5-fluoropyrimidine) was recrystallized from methanol+Hexane. Yield of the product was 70% of white crystals. Molecular weight 427 g/mol.

Reference： [1]Patent: US2007/72800,2007,A1 .Location in patent: Page/Page column 13

11
[ 866268-56-6 ]
[ 4125-93-3 ]
[ 931117-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile; at 70℃; for 144h;	Example 6; Dimethyl N-[2-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl) ethyl] -L-aspartate; [Show Image] (i) tert-Butyl N2-[2-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl)ethyl]-L-asparatate; The product (0.30 g) in step (vi) in Example 1 and L-aspartic acid tert-butyl ester (0.66 g) were heated in acetonitrile (3 ml) at 70C for 6 days. The reaction mixture was concentrated under reduced pressure. The residue was purified by RP HPLC to give the titled compound as a viscous solid. Yield: 0.28 g. 1H NMR delta (DMSO) 7.33 (1H, s), 7.06 (1H, s), 6.74 (2H, s), 4.16 (2H, t), 4.03 (3H, s), 3.87 (2H, t), 2.85-2.69 (2H, m), 2.46 (1H, dd), 2.23 (1H, dd), 2.19-2.11 (1H, m), 1.64 (2H, quintet), 1.40 (2H, sextet), 1.33 (9H, s), 0.92 (3H, t).

Reference： [1]Patent: EP1939200,2008,A1 .Location in patent: Page/Page column 26

12
[ 4125-93-3 ]
[ 173341-32-7 ]
[ 295322-44-0 ]

Reference： [1]Bioconjugate Chemistry,2010,vol. 21,p. 1225 - 1238

13
[ 4125-93-3 ]
[ 1246617-26-4 ]

Reference： [1]Chemical Communications,2011,vol. 47,p. 5825 - 5827
[2]Patent: US2012/95262,2012,A1

14
[ 4125-93-3 ]
[ 133125-17-4 ]

Reference： [1]Chemical Communications,2011,vol. 47,p. 5825 - 5827
[2]Patent: US2012/95262,2012,A1

15
[ 4125-93-3 ]
[ 78266-81-6 ]

Reference： [1]Chemical Communications,2011,vol. 47,p. 5825 - 5827
[2]Patent: US2012/95262,2012,A1
[3]Patent: WO2006/117552,2006,A1

16
[ 4125-93-3 ]
[ 1246617-28-6 ]

Reference： [1]Patent: US2012/95262,2012,A1

17
[ 4125-93-3 ]
[ 1246617-30-0 ]

Reference： [1]Patent: US2012/95262,2012,A1
[2]Patent: US2012/95262,2012,A1

18
[ 4125-93-3 ]
C₃₅H₅₈N₂O₉S [ No CAS ]

Reference： [1]Patent: US2012/95262,2012,A1

19
[ 4125-93-3 ]
[ 1493801-17-4 ]