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Chemical Structure| 36369-34-3 Chemical Structure| 36369-34-3

Structure of Cbz-3-F-Ala-OH
CAS No.: 36369-34-3

Chemical Structure| 36369-34-3

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Product Details of [ 36369-34-3 ]

CAS No. :36369-34-3
Formula : C11H12FNO4
M.W : 241.22
SMILES Code : O=C(O)[C@@H](NC(OCC1=CC=CC=C1)=O)CF
MDL No. :MFCD22372797
InChI Key :FXFJJOJQOPXMPP-VIFPVBQESA-N
Pubchem ID :12783166

Safety of [ 36369-34-3 ]

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

Computational Chemistry of [ 36369-34-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 6
Fraction Csp3 0.27
Num. rotatable bonds 7
Num. H-bond acceptors 5.0
Num. H-bond donors 2.0
Molar Refractivity 56.93
TPSA ?

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

75.63 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.61
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

1.41
Log Po/w (WLOGP)?

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

1.6
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.

1.29
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

1.1
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.4

Water Solubility

Log S (ESOL):?

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

-2.02
Solubility 2.29 mg/ml ; 0.00948 mol/l
Class?

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

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.6
Solubility 0.602 mg/ml ; 0.0025 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

-2.66
Solubility 0.533 mg/ml ; 0.00221 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.

-6.77 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)

2.68

Application In Synthesis of [ 36369-34-3 ]

* 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 [ 36369-34-3 ]

[ 36369-34-3 ] Synthesis Path-Downstream   1~5

  • 2
  • [ 918409-09-3 ]
  • [ 36369-34-3 ]
  • 3
  • [ 352636-78-3 ]
  • [ 36369-34-3 ]
  • 4
  • [ 35455-21-1 ]
  • [ 501-53-1 ]
  • [ 36369-34-3 ]
YieldReaction ConditionsOperation in experiment
In sodium hydroxide; Petroleum ether; (i) A solution of 0.535 g (5 mmol) of D,L-3-fluoroalanine in 1.25 ml (5 mmol) of 4 N sodium hydroxide was stirred at 5 C. while 0.935 g (5.5 mmol) of benzyl chloroformate and 1.5 ml (6 mmol) of 4 N sodium hydroxide were added alternately in five portions of each and while maintaining the temperature at below 10 C. and the pH at greater than 11. The mixture was stirred for a further 1 hour at 0 C. as the temperature was allowed to rise to room temperature. The mixture was stirred overnight at room temperature. 2 ml of ether were then added and the resulting mixture was stirred vigorously at room temperature for 1 hour. The organic and aqueous layers were separated and the aqueous layer was extracted with 5 ml of ether. The aqueous layer was cooled to 10 C. and treated dropwise with 1.2 ml of 5 N hydrochloric acid until the mixture became acid to Congo Red. The mixture was then stirred for a further 2 hours at 10 C. when a solid crystallized from the solution. This solid was filtered off and washed with a minimum volume of ice-cold water. The solid was dissolved in 10 ml of ether and the solution washed with two 10 ml portions of cold (0 C.) water. The ether solution was dried over sodium sulphate and evaporated to yield a solid which was triturated with petroleum ether. The solid was filtered off and dried to give 0.6 g of product of melting point 108-110 C. (decomposition). Recrystallisation of 0.1 g of this product from a mixture of 0.5 ml of ether and 0.5 ml of petroleum ether gave ca.60 mg of N-benzyloxycarbonyl-D,L-3-fluoroalanine of melting point 112-114 C. (decomposition).
(i) In a manner analogous to that described in Example 1, from 2.9 g (27 mmol) of L-3-fluoroalanine and 5.1 g (30 mmol) of benzyl chloroformate there were obtained 4.4 g of N-benzyloxycarbonyl-L-3-fluoroalanine of melting point 110-116 C. (decomposition; softening at 140 C.), [alpha]D20 = +5.4 (c = 0.5% in glacial acetic acid). Recrystallisation from a mixture of 25 ml of ether and 25 ml of petroleum ether gave 3.7 g of N-benzyloxycarbonyl-L-3-fluoroalanine of melting point 108-115 C. (decomposition; softening at 104 C.); [alpha]D20 = +5.6 (c = 0.5% in glacial acetic acid).
  • 5
  • [ 36369-34-3 ]
  • tert-butyl (2-((2S,5R,8S,11S,14S,17S,22S)-22-((S)-2-amino-4-((tert-butoxycarbonyl)amino)butanamido)-5-benzyl-11,14-bis(2-((tert-butoxycarbonyl)amino)ethyl)-17-((R)-1-hydroxyethyl)-8-isobutyl-3,6,9,12,15,18,23-heptaoxo1,4,7,10,13,16,19-heptaazacyclotricosan-2-yl)ethyl)carbamate [ No CAS ]
  • C61H93FN12O17 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; HATU; In N,N-dimethyl-formamide; for 0.666667h; HATU (0.55 g, 1 .46 mmol) in DMF (1 mL) was added, dropwise, to a solution of INT-1 1 (1 .41 g, 1 .33 mmol), CBZ-Fluoro-Alanine-OH (0.35 g, 1 .46mmol), and triethylamine (0.40 g, 3.98 mmol) in DMF (2 mL) over a period of 20 minutes. The mixture was stirred for an additional 20 minutes then applied directly to reversed phase liquid chromatography (RPLC) using an Isco Combiflash liquid chromatograph eluted with 10% to 95% acetonitrile and water using 0.1 % TFA modifier. The pure fractions were pooled and lyophilized to afford the CBZ-protected intermediate as white solid. The intermediate was stirred under 1 atmosphere of hydrogen in the presence of 5% Pd/C (100 mg) for 2 hours. The mixture was filtered, concentrated, and applied directly to reversed phase liquid chromatography (RPLC) using an Isco Combiflash liquid chromatograph eluted with 10% to 95% acetonitrile and water using no modifier. The pure fractions were pooled and lyophilized to afford the title compound as a white solid. Yield: 21 %, 2 steps. LC/MS [M+2H]/2 = 476.6 (loss of 2 Boc groups).
 

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