Structure of L-Threonine amide HCl
CAS No.: 33209-01-7
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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. : | 33209-01-7 |
Formula : | C4H11ClN2O2 |
M.W : | 154.60 |
SMILES Code : | N[C@@H]([C@H](O)C)C(N)=O.[H]Cl |
MDL No. : | MFCD00058288 |
InChI Key : | LZQCOMULTLYITH-MUWMCQJSSA-N |
Pubchem ID : | 45073228 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.75 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 3.0 |
Molar Refractivity | 35.08 |
TPSA ? Topological Polar Surface Area: Calculated from |
89.34 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.51 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.02 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.24 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.6 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.87 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.35 |
Solubility | 69.8 mg/ml ; 0.452 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.9 |
Solubility | 19.5 mg/ml ; 0.126 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
1.03 |
Solubility | 1660.0 mg/ml ; 10.7 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 |
-7.61 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 |
2.0 |
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) |
1.8 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In isopropyl alcohol; at 20℃; | L-threonine amide hydrochloride is prepared by the dropwise addition of 1.5 equivalents of thionyl chloride to a solution of 50 grams L-threonine in methanol, then heating the mixture to reflux. When reaction is complete, as shown by periodic TLC analysis, the reaction mixture is cooled and concentrated under vacuum. Isopropanol is added and the solvent is evaporated under vacuum to remove residual thionyl chloride, then additional isopropanol is added to increase the volume about two to four times. The reaction mixture is placed into an autoclave and stirred as ammonia gas is introduced to a final pressure of 50-60 psi (345-415 kPa), and stirring continues as the reaction progresses. After completion of the reaction, as shown by TLC analysis, the mixture is removed from the autoclave and filtered to remove solids, then concentrated under vacuum to about 100 mL. About 1.5 equivalents of isopropanol hydrochloride are added dropwise at room temperature, then the solid product is separated by filtration, washed with isopropanol and dried. The product is characterized by the following 1H NMR data (200 MHz, DMSO-d6): 1.1-1.2(d,3H), 3.3-3.4(s,OH), 3.5-3.6(d,1H), 3.9-4.1(sextet,1H), 5.5-5.7(d,NH2), 7.6-7.8(s,1 NH), 8.0-8.1(s,1 NH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36.2% | The N-tert-butoxycarbonyl-L-proline 1e (2.15 g, 10 mmol, using known method "Organic Letters, 2014, 16 (2), 432 - 435" prepared by the) dissolved in 50 ml dichloromethane in, adding 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide (2.3 g, 12 mmol), 1-hydroxy benzotriazole (1.62 g, 12 mmol) and N-methyl morpholine (3.3 ml, 30 mmol), stirring reaction for 1 hour, adding <strong>[33209-01-7]L-<strong>[33209-01-7]threonine amide hydrochloride</strong></strong> (1.55 g, 10 mmol, the Patent application "WO20050182262" disclosed method prepared), stirring for 16 hours. The reaction solution is added in 200 ml dichloromethane, for 1 M salt is washed with an acid (50 ml), anhydrous sodium sulfate drying, filtering, the filtrate is concentrated, with silica gel column chromatography using eluent system A purifying the obtained residue, to obtain the title compound 1 f (1.14 g, white foam solid), yield: 36.2percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50.9% | The (1S,3S,5S)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid 2a (191 mg, 0.84 mmol, the Patent application "WO2004052850" disclosed method is prepared) dissolved in 20 ml dichloromethane in, adding 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (192 mg, 1 mmol), 1-hydroxy benzotriazole (136 mg, 1 mmol) and N-methyl morpholine (0.28 ml, 2 . 52 mmol), stirring reaction for 1 hour, adding <strong>[33209-01-7]L-<strong>[33209-01-7]threonine amide hydrochloride</strong></strong> (130 mg, 0 . 84 mmol), stirring for 16 hours. The reaction solution is added in 100 ml dichloromethane, for 1 M salt is washed with an acid (20 ml), the organic phase is dried with anhydrous sodium sulfate, filtered, the filtrate is concentrated under reduced pressure, with silica gel column chromatography using eluent system A purifying the obtained residue, to obtain the title product 2 b (140 mg, white solid), yield: 50.9percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With 15-crown-5; caesium carbonate; copper(l) chloride; N,N`-dimethylethylenediamine; In toluene; at 110℃; for 18h;Schlenk technique; Sealed tube; Inert atmosphere; | General procedure: A 25-mL of Schlenk-type tube equipped with a magnetic stir bar was charged with a chiral amino acid amide or its hydrochloride (1.2 mmol), Cs2CO3 (2.0 mmol; 3.0 mmol used when amino acid amide hydrochloride was used), and CuCl (0.1mmol) before sealing. A syringe was used under a nitrogen atmosphere to add aryl halide (1.0mmol), DMEDA (1.0 mmol), toluene (4.0 mL) and 15-Crown-5 (0.2mmol). The tube was put into an oil bath pot preheated at 110°C and was stirred at a steady temperature for 18 h. The reaction mixture was then cooled to room temperature, quenched with water, and extracted with ethyl acetate (20 mL) for three times. The organic layers were combined, dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with a solution of dichloromethane and ethyl alcohol (80/1 to 10/1) to afford the chiral alpha-amino anilides. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.2% | With 4-methyl-morpholine; isobutyl chloroformate; In N,N-dimethyl-formamide; at -15 - 20℃;Inert atmosphere; | A four-necked flask was charged with a solution of Fmoc-Pro-OH (337 g, 1 mol) in DMF containingNMM (101 g, 1 mol) under nitrogen, which was cooled to -20 °C, IBCF was added dropwise to thereaction vessel while maintaining the reaction mixture below -15 °C. 1 was added as solids in oneportion to the reaction mixture at the same temperature, followed by dropwise addition of NMM(101 g, 1 mol). After the completion of the addition, the reaction mixture was gradually warmed toroom temperature. 1 L of water was poured into the reaction mixture under vigorous stirring, followedby addition of the seed crystal resulting in white solid formed, which was then filtered and dried withoven to afford 2 585 g (89.2percent yield). 1H-NMR (400 MHz, DMSO-d6) delta7.98?7.56 (m, 5H), 7.50?7.29(m, 4H), 7.14 (m, 2H), 4.86 (dd, J = 18.2, 5.3 Hz, 1H), 4.58?4.13 (m, 4H), 4.13?3.94 (m, 2H), 3.56?3.36(m, 2H), 2.31?1.76 (m, 4H), 1.00 (dd, J = 14.9, 6.3 Hz, 3H). 13C-NMR (101 MHz, DMSO-d6) delta172.64,172.39, 154.80, 144.38, 141.23, 128.17, 127.67, 125.64, 120.58, 67.17, 66.89, 60.54, 60.42, 58.41, 47.09, 24.46,23.46, 20.53. HRMS (ESI-TOF+) m/z ([M + H]+), calcd. for C24H27N3O5 + H+: 438.4960, found 438.2026. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.5% | N-Cbz-ThrNH2 (504 g, 2 mol) was dissolved in methanol, followed by addition of 10percent of Pd/C(50.4 g, 10 wt percent), and the resulting suspension was stirred at room temperature under hydrogen(1.0 MPa) for 12 h. Pd/C was filtered and the filtrate was evaporated in vacuum to furnish the crudeproduct as yellowish oily liquid, which was redissolved in 3 L of acetone, followed by slow addition ofa solution of HCl in iPrOH (500 mL) at 0?5 °C under stirring. The precipitated white solid was filteredand dried under high vacuum (45 °C, 0.1 MPa) to afford 1b 289 g (93.5percent yield). 1H-NMR (400 MHz,D2O) delta 4.15 (p, J = 6.1 Hz, 1H), 3.86 (d, J = 5.2 Hz, 1H), 1.25 (d, J = 6.5 Hz, 3H). 13C-NMR (101 MHz,D2O) delta170.25, 66.04, 58.40, 18.80. HRMS (ESI-TOF+) m/z ([M + H]+), calcd. for C4H11N2O2 + H+:119.0815, found 119.0817. |
A416752 [49705-99-9]
(2S,3R)-2-Amino-3-hydroxybutanamide
Reason: Free-salt