Structure of H-D-β-Ala(3-Me)-OH
CAS No.: 3775-73-3
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
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 |
63.32 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.75 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-3.06 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.19 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.39 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.73 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.73 |
Log S (ESOL):? ESOL: Topological method implemented from |
1.58 |
Solubility | 3920.0 mg/ml ; 38.1 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (Ali)? Ali: Topological method implemented from |
2.29 |
Solubility | 20300.0 mg/ml ; 197.0 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
0.34 |
Solubility | 225.0 mg/ml ; 2.18 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-9.1 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
3.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.18 |
* 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.
Yield | Reaction Conditions | Operation 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+ |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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+). |
Yield | Reaction Conditions | Operation 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%. |