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Chemical Structure| 13726-69-7 Chemical Structure| 13726-69-7

Structure of Boc-Hyp-OH
CAS No.: 13726-69-7

Chemical Structure| 13726-69-7

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Product Details of [ 13726-69-7 ]

CAS No. :13726-69-7
Formula : C10H17NO5
M.W : 231.25
SMILES Code : O=C(O)[C@H]1N(C(OC(C)(C)C)=O)C[C@H](O)C1
MDL No. :MFCD00053370
InChI Key :BENKAPCDIOILGV-RQJHMYQMSA-N
Pubchem ID :88804

Safety of [ 13726-69-7 ]

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

Computational Chemistry of [ 13726-69-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 4
Num. H-bond acceptors 5.0
Num. H-bond donors 2.0
Molar Refractivity 59.53
TPSA ?

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

87.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.69
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

0.25
Log Po/w (WLOGP)?

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

0.06
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.

-0.07
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

-0.64
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.26

Water Solubility

Log S (ESOL):?

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

-1.17
Solubility 15.7 mg/ml ; 0.068 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.

-1.64
Solubility 5.31 mg/ml ; 0.023 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

0.43
Solubility 621.0 mg/ml ; 2.69 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.

-7.53 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

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.56

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)

3.14

Application In Synthesis of [ 13726-69-7 ]

* 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 [ 13726-69-7 ]

[ 13726-69-7 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 100-39-0 ]
  • [ 13726-69-7 ]
  • [ 40350-83-2 ]
YieldReaction ConditionsOperation in experiment
General procedure: Synthesis of 1m-p 200 mg (0.86 mmol) of (2S,4R), (2S,4S), (2R,4R), or (2R,4S)-Boc-Hyp was dissolved in 3 ml of tetrahydrofuran, cooled to 0 C., and 103 mg (3 eq.) of 60% sodium hydride was added. The mixture was stirred cold for 20 minutes, then 226 ul (2.2 eq) of benzyl bromide was added. The mixture was allowed to warm to room temperature and stirred for 16 hours, at which time it was cooled to 0 C. and 1 ml of water was added, followed by 500 uL of 5% citric acid and 2 mL of saturated sodium bicarbonate solution. The organic layer was separated, and the aqueous phase was washed twice with 1 ml portions of ethyl acetate. The aqueous layer was then acidified to pH2.0 with citric acid, and extracted three times with 2 ml portions of ethyl acetate. The combined organic layers were washed with saturated sodium chloride solution, the solvent removed under reduced pressure, the residues were dissolved in 2 ml of methylene chloride, and 2 ml of 4M HCl in dioxane was added. The mixture was stirred for 12 hours, and the solvent removed under reduced pressure, yielding the HCl salts 3m-p. 300 uM of each was then converted first to 5m-p, then the final product 1m-p as the TFA salt via the methods described earlier for 1h-1.
With sodium hydride; In tetrahydrofuran; mineral oil; at 0℃; for 6h;Reflux; The Boc-protected L-Hyp 3 was dissolved in THF (100mL) and then cannulated into a slurry of NaH (60% inmineral oil, 11.2 g, 155 mmol) in THF (200 mL) at 0 C.Benzyl bromide (15.0 g, 87.7 mmol) was added dropwise tothe reaction mixture. The flask was warmed to room temperatureand then the mixture was heated under reflux for 6h. The reaction mixture was cooled to room temperature andpoured over ice. The organic solvent was evaporated underreduced pressure and the aqueous solution was washed withEtOAc. The aqueous phase was acidified with 2N HCl untilthe pH was 2, and then it was extracted with EtOAc. Theorganic phase was concentrated under reduced pressure toyield 4 as a brownish yellow oil. This brownish yellow oilwas dissolved in dry THF (300 mL) and cooled to 0 C.BH3·DMS (5.7 mL, 58 mmol) was added dropwise to thereaction mixture, which was then kept stirring at 0 C for anadditional 1 h. The flask was removed from the ice bath, andthe mixture stirred overnight at room temperature. Thereaction mixture was poured over ice and sequentiallyextracted with EtOAc, washed with saturated aqueousNaHCO3, washed with brine, and dried (Na2SO4). Thesolution was concentrated under reduced pressure andpurified through flash column chromatography (FCC; gradientEtOAc/hexanes, from 30 to 50%) to yield 5 [26] as aslightly yellow oil (16.3 g, 70% over three steps).
  • 3
  • [ 13726-69-7 ]
  • [ 474417-79-3 ]
 

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