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Chemical Structure| 33209-01-7 Chemical Structure| 33209-01-7

Structure of L-Threonine amide HCl
CAS No.: 33209-01-7

Chemical Structure| 33209-01-7

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Product Details of [ 33209-01-7 ]

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

Safety of [ 33209-01-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 33209-01-7 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

89.34 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

-0.51
Log Po/w (WLOGP)?

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

-1.02
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.

-1.24
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

-1.6
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.87

Water Solubility

Log S (ESOL):?

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

-0.35
Solubility 69.8 mg/ml ; 0.452 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.

-0.9
Solubility 19.5 mg/ml ; 0.126 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

1.03
Solubility 1660.0 mg/ml ; 10.7 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.

-7.61 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)

1.8

Application In Synthesis of [ 33209-01-7 ]

* 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 [ 33209-01-7 ]

[ 33209-01-7 ] Synthesis Path-Downstream   1~17

  • 1
  • [ 20866-56-2 ]
  • [ 33209-01-7 ]
  • [ 123970-51-4 ]
  • 2
  • [ 33209-01-7 ]
  • [ 131949-99-0 ]
  • Boc-Asp(Thr-NH2)-Phe-NMeBzl [ No CAS ]
  • 3
  • [ 33209-01-7 ]
  • [ 131948-60-2 ]
  • (1H-indol-2-ylcarbonyl)-Asp(Thr-NH2)-Phe-NMeBzl [ No CAS ]
  • 4
  • [ 33209-01-7 ]
  • [ 131949-12-7 ]
  • (1H-indol-3-ylcarbonyl)-Asp(Thr-NH2)-Phe-NMeBzl [ No CAS ]
  • 5
  • [ 33209-01-7 ]
  • [ 830-03-5 ]
  • [ 60828-33-3 ]
  • 6
  • [ 60143-52-4 ]
  • [ 33209-01-7 ]
  • 7
  • [ 33209-01-7 ]
  • C68H77N11O13S2 [ No CAS ]
  • C72H83N11O15S2 [ No CAS ]
  • 8
  • [ 13734-34-4 ]
  • [ 33209-01-7 ]
  • [(S)-1-((1S,2R)-1-Carbamoyl-2-hydroxy-propylcarbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester [ No CAS ]
  • 9
  • [ 33209-01-7 ]
  • [ 14609-03-1 ]
  • [ 219319-51-4 ]
  • 10
  • [ 33209-01-7 ]
  • [ 104504-43-0 ]
  • [(S)-2-(4-Benzoyl-phenyl)-1-((1S,2R)-1-carbamoyl-2-hydroxy-propylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester [ No CAS ]
  • 11
  • [ 33209-01-7 ]
  • [ 91990-87-3 ]
  • [ 219319-52-5 ]
  • 12
  • [ 49705-99-9 ]
  • [ 33209-01-7 ]
YieldReaction ConditionsOperation 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).
  • 13
  • [ 15761-39-4 ]
  • [ 33209-01-7 ]
  • (S)-2-(((2S,3R)-1-amino-3-hydroxy-1-oxobutane-2-yl)carbamoyl)pyrrolidine-1-formic acid tert-butyl [ No CAS ]
YieldReaction ConditionsOperation 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.
  • 14
  • [ 33209-01-7 ]
  • [ 197142-36-2 ]
  • (1S,3S,5S)-3-(((2S,3R)-1-amino-3-hydroxy-1-oxobutane-2-yl)carbamoyl)-2-azabicyclo[3.1.0]hexane-2-formic acid tert-butyl [ No CAS ]
YieldReaction ConditionsOperation 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.
  • 15
  • [ 591-50-4 ]
  • [ 33209-01-7 ]
  • (2S,3R)-2-amino-3-hydroxy-N-phenylbutanamide [ No CAS ]
YieldReaction ConditionsOperation 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.
  • 16
  • [ 71989-31-6 ]
  • [ 33209-01-7 ]
  • Fmoc-Pro-ThrNH<SUB>2</SUB> [ No CAS ]
YieldReaction ConditionsOperation 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.
  • 17
  • [ 49705-98-8 ]
  • [ 33209-01-7 ]
YieldReaction ConditionsOperation 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.
 

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