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Chemical Structure| 77449-94-6 Chemical Structure| 77449-94-6

Structure of H-cis-D-Hyp-OH·HCl
CAS No.: 77449-94-6

Chemical Structure| 77449-94-6

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Product Details of [ 77449-94-6 ]

CAS No. :77449-94-6
Formula : C5H10ClNO3
M.W : 167.59
SMILES Code : Cl.O[C@H]1CN[C@H](C1)C(=O)O
MDL No. :MFCD09749867
InChI Key :YEJFFQAGTXBSTI-VKKIDBQXSA-N
Pubchem ID :12310682

Safety of [ 77449-94-6 ]

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

Computational Chemistry of [ 77449-94-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 3.0
Molar Refractivity 40.65
TPSA ?

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

69.56 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

-2.37
Log Po/w (WLOGP)?

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

-0.78
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.

-3.07
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

-0.67
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-1.38

Water Solubility

Log S (ESOL):?

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

0.68
Solubility 802.0 mg/ml ; 4.79 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.

1.45
Solubility 4700.0 mg/ml ; 28.0 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

0.66
Solubility 763.0 mg/ml ; 4.55 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.

-9.01 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)

2.31

Application In Synthesis of [ 77449-94-6 ]

* 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 [ 77449-94-6 ]

[ 77449-94-6 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 67-56-1 ]
  • [ 77449-94-6 ]
  • [ 114676-59-4 ]
YieldReaction ConditionsOperation in experiment
100% With thionyl chloride; at 0 - 75℃; for 4.5h; Cis-4-hydroxy-D-proline hydrochloride 3A (12.8 g, 76.38 mmol) was dissolved in anhydrous methanol (120 mL) at room temperature,Cooled to 0 , dichloro sulfoxide (10.27g, 86.31mmol),Heated to 75 C, refluxed for 4.5 hours, and allowed to react overnight at room temperature.The solvent was taken off in vacuo to give a white solid 3B (13.83 g, yield 100%).
With thionyl chloride; at 0 - 20℃; for 6h; PREPARATION 26 (2R,4R)-4-Hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester Add thionyl chloride (1.81 mol, 213.8 g, 1.5 eq) drop wise to a solution of (2R,4R)-4-hydroxy-pyrrolidine-2-carboxylic acid hydrochloride (1.19 mol, 200 g) in dry methanol (2 L) at 0 C. under a nitrogen atmosphere. Upon complete addition, warm the reaction mixture to room temperature and stir for 6 h. Concentrate the reaction mixture under reduced pressure to obtain the corresponding methyl ester hydrochloride.
With thionyl chloride; for 3h;Reflux; To a solution of A (16.56 g, 98.8 mmol) in CH3OH (150 mL) was added SOCI2 (35.26 g, 296.4 mmol) at room temperature and the mixture was heated to reflux for 3 h. The solvent was removed in vacuo and the off-white solid obtained was used in next step without further purification.
With thionyl chloride; at 0 - 60℃; for 4h;Inert atmosphere; To a solution of17 (20 mmol, 3.36 g) in anhydrousMeOH (40 mL) was added dropwise thionyl chloride (24 mmol, 1.74 mL) at 0 Cunder N2 atmosphere. The mixture was stirred at 60 C for 4 h. After completion of thereaction (monitored by TLC), the resulting mixture was concentrated in vacuo to give the crude product 18 as a white solid, the crude productwas used directly without further purification. 1H NMR (400 MHz, D2O) delta4.66-4.61 (m, 2H), 3.82 (s, 3H), 3.47-3.40 (m, 2H), 2.52-2.33 (m, 2H). 13C NMR (100 MHz, D2O) delta 170.7,68.9, 58.4, 53.8, 53.4, 36.7.
With thionyl chloride; at 0 - 80℃; for 3.5h; cis-4-Hydroxy-D-proline hydrochloride (200 g, 1.19 mol) was dissolved in MeOH (2 L) in four-neck flask (equipped with mechanical stirrer, reflux condenser, dropping funnel and septum) and was cooled to 0 C. Thionyl chloride (95.8 mL, 1.31 mol) was added dropwise to the reaction mixture for 1.5 h (maintain a temperature 0 C.). The reaction mixture was warmed to room temperature for 1 h and heated to reflux for 1 h. The reaction mixture was cooled to room temperature (overnight), transferred to round-bottom-flask and concentrated. The gel-like residue was evaporated with CHCl3 (3*1 L) and dried under high vacuum for 1 h at 50 C. (water bath). The residue was crumbled with spatula, suspended in Et2O (1 L) and placed in ultrasound bath for 40 minutes (2*20 minutes). The white solid was filtered, washed with Et2O (2*0.5 L) and dried under high vacuum for 4 h at 50 C. (water bath) to give 234.6 g of the crude product that was used in the next step without further purification. ESI+MS m/z=146 (M+1)+; 1H NMR (700 MHz, D2O) delta 4.75 (d, J=3.1 Hz, 1H), 4.74 (d, J=3.0 Hz, 1H), 4.70 (qt, J=4.2, 1.6 Hz, 2H), 3.92 (s, 7H), 3.57-3.50 (m, 5H), 2.59 (ddd, J=14.4, 10.1, 4.2 Hz, 3H), 2.51-2.47 (m, 2H).

 

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