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Chemical Structure| 3775-73-3 Chemical Structure| 3775-73-3

Structure of H-D-β-Ala(3-Me)-OH
CAS No.: 3775-73-3

Chemical Structure| 3775-73-3

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Product Details of [ 3775-73-3 ]

CAS No. :3775-73-3
Formula : C4H9NO2
M.W : 103.12
SMILES Code : C[C@@H](N)CC(O)=O
MDL No. :MFCD00211284
InChI Key :OQEBBZSWEGYTPG-GSVOUGTGSA-N
Pubchem ID :5706670

Safety of [ 3775-73-3 ]

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

Computational Chemistry of [ 3775-73-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 0
Fraction Csp3 0.75
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 25.82
TPSA ?

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

63.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.75
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

-3.06
Log Po/w (WLOGP)?

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

-0.19
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

-0.73
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.73

Water Solubility

Log S (ESOL):?

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

1.58
Solubility 3920.0 mg/ml ; 38.1 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

2.29
Solubility 20300.0 mg/ml ; 197.0 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

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

0.34
Solubility 225.0 mg/ml ; 2.18 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.

-9.1 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

3.0
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)

1.18

Application In Synthesis of [ 3775-73-3 ]

* 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 [ 3775-73-3 ]

[ 3775-73-3 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 3775-73-3 ]
  • [ 86-14-6 ]
  • 2
  • [ 21948-18-5 ]
  • [ 3775-73-3 ]
  • 3
  • [ 75-15-0 ]
  • [ 3775-73-3 ]
  • [ 74-88-4 ]
  • D-(-)-β-Amino-buttersaeure-methyl-dithiocarbamat [ No CAS ]
  • 4
  • [ 75-77-4 ]
  • [ 3775-73-3 ]
  • [ 139243-54-2 ]
  • 5
  • [ 3775-73-3 ]
  • [ 383-63-1 ]
  • [ 158462-50-1 ]
  • 7
  • [ 3775-73-3 ]
  • [ 98-88-4 ]
  • [ 113034-29-0 ]
  • 8
  • [ 132540-67-1 ]
  • [ 3775-73-3 ]
  • 9
  • [ 141632-86-2 ]
  • [ 3775-73-3 ]
  • 12
  • (R)-3-Azidobuttersaeure [ No CAS ]
  • [ 3775-73-3 ]
  • 13
  • 2-[(R)-3-((4R,5S)-3,4-Dimethyl-2-oxo-5-phenyl-imidazolidin-1-yl)-1-methyl-3-oxo-propyl]-isoindole-1,3-dione [ No CAS ]
  • [ 3775-73-3 ]
  • 14
  • [ 623-43-8 ]
  • [ 3775-72-2 ]
  • [ 3775-73-3 ]
  • 15
  • [ 394220-59-8 ]
  • [ 3775-73-3 ]
  • 16
  • [ 120686-16-0 ]
  • [ 3775-73-3 ]
  • 17
  • [ 3775-73-3 ]
  • [ 501-53-1 ]
  • [ 67843-72-5 ]
  • 18
  • [ 1067647-39-5 ]
  • [ 3775-73-3 ]
  • 19
  • [ 540-88-5 ]
  • [ 3775-73-3 ]
  • [ 120686-16-0 ]
  • 20
  • ethyl 3-butanamidobutanoate [ No CAS ]
  • [ 3775-72-2 ]
  • [ 3775-73-3 ]
  • [ 1379442-82-6 ]
  • [ 1270112-24-7 ]
  • [ 5303-65-1 ]
  • [ 5303-65-1 ]
  • ethyl (R)-3-butanamidobutanoate [ No CAS ]
  • ethyl (S)-3-butanamidobutanate [ No CAS ]
  • 22
  • [ 3775-73-3 ]
  • [ 1392838-76-4 ]
  • [ 1392843-06-9 ]
YieldReaction ConditionsOperation in experiment
With sodium methylate; In 2-methoxy-ethanol; for 3.0h;Reflux; Example 142(i?)-3-[(l-Benzyl-5-hydroxy-2-oxo-3-phenyl-l,2-dihydro-[l,7]naphthyridine-6-carbonyl)- amino] -butyric acid[0464] A mixture of l-benzyl-5-hydroxy-2-oxo-3-phenyl-l,2-dihydro-[l,7]naphthyridine-6- carboxylic acid methyl ester (35 mg, 0.090 mmol), (R)-3-amino-butyric acid (94 mg, 0.90 mmol) and NaOMe (39 mg, 0.73 mmol) in 2-methoxyethanol (10 mL) was refluxed for 3 h. After the mixture was cooled to r.t., the solvent was evaporated in vacuo. The residue was dissolved in saturated NaHC03 and washed with ether. The aqueous layer was acidified to pH about 2 with 6 M HCl, and the resulting precipitate was isolated by filtration to give 28 mg of the title compound as a yellow solid. MS: (+) m/z 458.30 (M+
  • 23
  • [ 3775-73-3 ]
  • [ 24424-99-5 ]
  • [ 159991-23-8 ]
YieldReaction ConditionsOperation in experiment
90% With triethylamine; In 1,4-dioxane; water; at 0 - 20℃; for 16.0h; Intermediate 72: (4S,7R,10aS)-4-Amino-7-methylhexahydro-2H-pyrido[2, l- b] [ 1 ,3 ]thiazepin-5(7H)-one.A: (R)-3-(tert-Butoxycarbonylamino)butanoic acid [00344] To a stirred suspension of <strong>[3775-73-3](R)-3-aminobutanoic acid</strong> (2.415 g, 23.42 mmol) in dioxane (15 mL) and water (15.00 mL) was added TEA (4.90 mL, 35.1 mmol) dropwise. To the resulting light brown solution cooled at 0 C was added portionwise di-tert-butyl carbonate (4.69 g, 26.9 mmol). The mixture was then stirred at rt for 16 hr. The reaction mixture was partitioned between water (80 mL) and EtOAc (80 mL). The separated aqueous layer was washed with EtOAc and acidified with 1 M aqueous KHSO4 to pH = 3 and extracted with EtOAc (2x). The combined EtOAc extracts were washed with saturated aqueous NaCl (2x), dried over Na2S04, filtered and concentrated to give (R)-3- (tert-butoxycarbonylamino)butanoic acid (4.301 g, 21.16 mmol, 90% yield) as a pale yellow solid. XH NMR (400 MHz, CDC13) delta ppm 4.92 (s, 1H), 4.14 - 3.96 (m, 2H), 2.56 (d, J = 5.2 Hz, 2H), 1.45 (s, 9H), 1.25 (d, J = 6.9 Hz, 3H).
  • 24
  • [ 3775-73-3 ]
  • [ 1455091-23-2 ]
  • [ 1455088-28-4 ]
YieldReaction ConditionsOperation in experiment
75% With sodium methylate; In N,N-dimethyl-formamide; at 140℃; for 4.0h;Microwave irradiation; Sealed tube; l-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (75 mg, 0.234 mmol) and 3-(R)-amino-butyric acid (103 mg, 1.0 mmol) were placed in a CEM 10 mL Microwave vessel and dissolved in anhydrous N,N-dimethylformamide (2 mL.) Sodium methoxide (54 mg, 1.0 mmol) was added to solution and the vessel was sealed. The reaction was heated to 140 C in a CEM microwave apparatus for four hours. Upon completion, the reaction mixture was diluted with water and treated with IN hydrochloric acid. The precipitate was dissolved in dichloromethane and dried over anhydrous sodium sulfate. The crude product was purified by MPLC (methylene chloride- ethyl acetate) to provide the title compound as a light-yellow solid in 75% yield. MS ESI(-) m/e: 390.091 (M-l).
  • 25
  • [ 3775-73-3 ]
  • [ 107-18-6 ]
  • [ 1460306-61-9 ]
YieldReaction ConditionsOperation in experiment
At 0C, 4 M HCI-dioxane (37.8 mL, 151 mmol) was added dropwise to a mixture of (R)-homo-3-alanine (35; 13.0 g, 126 mmol) in CH2CI2 (170 mL). PCI5 (31.5 g, 151 mmol) was added to the suspension. The mixture was stirred at 0C to rt for 15 h. A clear solution resulted. The volatiles were evaporated. The residue was dissolved in CH2CI2 (150 mL). Allyl alcohol (10.3 mL, 151 mmol) was added slowly and the mixture was stirred for 2 h at rt. The volatiles were evaporated to afford crude 36 HCI (25.6 g).
  • 26
  • [ 107-93-7 ]
  • [ 3775-73-3 ]
  • 27
  • [ 64-18-6 ]
  • [ 3775-73-3 ]
  • [ 1620680-34-3 ]
YieldReaction ConditionsOperation in experiment
13.6 g With acetic anhydride; In water; at 0 - 20℃; for 4.16667h; To a solution of <strong>[3775-73-3](R)-3-aminobutanoic acid</strong> (10.8 g, 105 mmol) in 1 15 mL of 80% formic acid was added dropwise 70 mL of acetic anhydride at 0 C, stirred for 10 min, then stirred for 4 h at r.t. The reaction mixture was quenched with water (70 mL), concentrated. The residue was recrystallized from water to afford the title compound (13.6 g).
  • 28
  • [ 3775-73-3 ]
  • C4H8ClNO [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; phosphorus pentachloride; In 1,4-dioxane; dichloromethane; at 0 - 20℃; for 15.0h; At 0 C., 4 M HC1-dioxane (37.8 mE, 151 mmol) was added dropwise to a mixture of (R)-homo-13-alanine (35; 13.0 g, 126 mmol) in CH2C12 (170 mE). PC15 (31.5 g, 151 mmol) was added to the suspension. The mixture was stirred at 0 C. to it for 15 h. A clear solution resulted. The volatiles were evaporated. The residue was dissolved in CH2C12 (150 mE). Allyl alcohol (10.3 mE, 151 mmol) was added slowly and the mixture was stirred for 2 h at it. The volatiles were evaporated to afford crude 36.HC1 (25.6 g).
  • 29
  • [ 3775-73-3 ]
  • [ 14527-26-5 ]
  • (3R)-3-carbamimidamidobutanoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With sodium hydroxide; In methanol; water; at 20℃; for 72.0h; Synthesis of Compound 219 (fi)-Aminobutyric acid SM01 (750 mg, 7.27 mmol) and 2-methyl-2-thiopseudourea sulfate (MTS, 1 .21 g, 4.36 mmol) were suspended in methanol (4 m L). After addition of 3N sodium hydroxide in water (2.62 mL, 1 .09 eq.), the clear solution was stirred for 3 days at room temperature. Subsequently, the white precipitate was filtered off and washed with water/methanol (15 mL, 1 /2). The white powder was air dried for 1 hour and then put under high vacuum for 2 days to yield the (3R)-3-carbamimidamidobutanoic acid (21 9) as a white solid (879 mg, 83%) ; 1 H-NMR (300 MHz, D20) : 5 3.81 (m , 1 H), 2.31 (m, 2H), 1 .15 (d, 3H) ; ES(pos)MS m/z 146.1 (M+H+).
  • 30
  • 3-butanamidobutanoic acid tert-butyl ester [ No CAS ]
  • [ 3775-73-3 ]
  • (S)-3-butanamidobutanoic acid tert-butyl ester [ No CAS ]
  • 31
  • [ 3775-73-3 ]
  • [ 3970-37-4 ]
  • (R)-3-((2-bromo-6-nitrophenyl)amino)butanoic acid [ No CAS ]
  • 32
  • [ 3775-73-3 ]
  • [ 58534-94-4 ]
  • (R)-3-((2-bromo-6-nitrophenyl)amino)butanoic acid [ No CAS ]
  • 33
  • [ 946126-94-9 ]
  • [ 3775-73-3 ]
  • (R)-3-((2-(methoxycarbonyl)-6-nitrophenyl)amino)butanoic acid [ No CAS ]
  • 34
  • [ 67-56-1 ]
  • [ 3775-73-3 ]
  • [ 6078-06-4 ]
YieldReaction ConditionsOperation in experiment
98.5% With thionyl chloride; at 0 - 10℃;Reflux; Put 240g methanol, 50g (R) -3-aminobutyric acid in the clean reaction bottle, cool with ice water, the temperature drops to 0 10 , and slowly add 66.4g sulfoxide chloride dropwise. After the dropwise addition, the temperature was raised to reflux reaction until the raw materials disappeared.The reaction solution is directly concentrated under reduced pressure to obtain the product.Yield: 98.5%, purity: 99.7%, ee: 99.9%.
  • 35
  • [ 3775-73-3 ]
  • 1-bromo-4-chloro-2-fluoro-3-nitrobenzene [ No CAS ]
  • (R)-3-((6-bromo-3-chloro-2-nitrophenyl)amino)butanoic acid [ No CAS ]
 

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