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Chemical Structure| 6306-52-1 Chemical Structure| 6306-52-1

Structure of H-Val-OMe·HCl
CAS No.: 6306-52-1

Chemical Structure| 6306-52-1

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Synonyms: H-Val-OMe.HCl

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Product Details of [ 6306-52-1 ]

CAS No. :6306-52-1
Formula : C6H14ClNO2
M.W : 167.63
SMILES Code : N[C@@H](C(C)C)C(OC)=O.[H]Cl
Synonyms :
H-Val-OMe.HCl
MDL No. :MFCD00012497
InChI Key :KUGLDBMQKZTXPW-JEDNCBNOSA-N
Pubchem ID :111190

Safety of [ 6306-52-1 ]

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

Computational Chemistry of [ 6306-52-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 0.83
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 41.91
TPSA ?

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

52.32 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

1.37
Log Po/w (WLOGP)?

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

0.94
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.

0.75
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

0.0
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.61

Water Solubility

Log S (ESOL):?

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

-1.54
Solubility 4.79 mg/ml ; 0.0285 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.

-2.07
Solubility 1.42 mg/ml ; 0.00848 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < 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

-0.43
Solubility 61.9 mg/ml ; 0.369 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

Yes
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.

-6.35 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

1.0
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)

1.57

Application In Synthesis of [ 6306-52-1 ]

* 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 [ 6306-52-1 ]

[ 6306-52-1 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 6306-52-1 ]
  • [ 501-53-1 ]
  • [ 13139-28-1 ]
  • 2
  • [ 4474-86-6 ]
  • [ 6306-52-1 ]
  • [ 17460-89-8 ]
  • 3
  • [ 6306-52-1 ]
  • [ 116838-52-9 ]
  • (S)-2-(1-pyrrolyl)propionyl-L-valine methyl ester [ No CAS ]
  • 5
  • [ 6306-52-1 ]
  • [ 128376-65-8 ]
  • C18H26BNO4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; at 20℃; for 72h;Molecular sieve;Product distribution / selectivity; A mixture of L-Valine methyl ester hydrochloride (548 mg), 4-(5,5-dimethyl- [1 ,3,2]dioxaborinan-2-yl)-benzaldehyde (476 mg) and molecular sieves in anhydrous THF (17 ml_) was stirred at room temperature for three days. Then, the mixture was cooled to O0C and a solution of NaBH3CN (155 mg) in dry MeOH (3 ml_) was added dropwise. The mixture was stirred at room temperature for 4 hours and the solids were removed by filtration. The filtrate was evaporated under vacuum to yield the desired product (632 mg) that was used in the next reaction without further purification.
  • 6
  • [ 6306-52-1 ]
  • [ 37091-73-9 ]
  • [ 1032629-90-5 ]
  • 7
  • [ 6306-52-1 ]
  • [ 198561-07-8 ]
  • [ 1417532-34-3 ]
  • 8
  • tetrabutylphosphonium alaninate [ No CAS ]
  • [ 6306-52-1 ]
  • [ 1115-74-8 ]
  • 9
  • [ 10601-99-7 ]
  • [ 6306-52-1 ]
  • C15H17NO3 [ No CAS ]
  • 10
  • [ 6306-52-1 ]
  • [ 23361-28-6 ]
  • [ 174881-62-0 ]
YieldReaction ConditionsOperation in experiment
45% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 25℃; for 20h; Compound 2 (0.450 g, 1.43 mmol) was dissolved in 4 mL DMF. To this was added HBTU (0.619 g, 1.63 mmol) and DIEA (0.48 mL, 2.73 mmol) to generate the activated ester. After 10 min, l-Valine methyl ester hydrochloride (0.23 g, 1.37 mmol) was added and the reaction mixture was stirred under nitrogen overnight. The reaction was diluted with EtOAc (20 mL) and an equal amount of sodium bicarbonate, washed with brine (6 * 20 mL), dried (MgSO4) and concentrated in vacuo. The crude product was subjected to column chromatography (Hexane/EtOAc, 2:3 v/v) yielding 8 as a white solid (0.26 g, 45%). 1H NMR (400 MHz, CDCl3) δ 7.21 (d, J = 8.4 Hz, 1H, 1 * P1-Val-NH), 5.25 (d, J = 9.3 Hz, 1H, 1 * P3-Val-carbamate-NH), 4.64-4.54 (m, 1H, 1 * P1-Val-αH), 4.42 (dd, J = 8.4, 5.1 Hz, 1H, 1 * P2-Pro-αH), 4.29 (dd, J = 9.4, 6.2 Hz, 1H, 1 * P3-Val-αH), 3.72 (s, 3H, OCH3), 3.78-3.66 (m, 1H, 1 * P2-Pro-δH), 3.64-3.54 (m, 1H, 1 * P2-Pro-δH), 2.40-2.28 (m, 1H, 1 * P1-Val-βH), 2.19-2.03 (m, 2H, 2 * P2-Pro-βH), 2.01-1.91 (m, 2H, 1 * P3-Val-βH and 1 * P2-Pro-γH), 1.88-1.75 (m, 1H, 1 * P2-Pro-γH), 1.42 (s, 9H, tButyl), 0.98 (d, J = 6.8 Hz, 3H, 3 * P1-Val-γH), 0.94-0.87 (m, 9H, 3 * P1-Val-γH and 6 * P3-Val-γH). 13C NMR (101 MHz, CDCl3) δ 172.58, 172.12, 170.92, 155.80, 79.56, 59.92, 57.54, 56.77, 52.04, 47.68, 31.43, 31.09, 28.32, 27.20, 25.15, 19.55, 18.94, 17.86, 17.40. ESI-MS (m/z): calcd for C21H37N3NaO6 (M + Na) m/z 450.2580 found 450.2540.
  • 11
  • [ 676448-17-2 ]
  • [ 6306-52-1 ]
  • C19H26N2O4 [ No CAS ]
 

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