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Chemical Structure| 78269-85-9 Chemical Structure| 78269-85-9

Structure of Teoc-OSu
CAS No.: 78269-85-9

Chemical Structure| 78269-85-9

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Product Details of [ 78269-85-9 ]

CAS No. :78269-85-9
Formula : C10H17NO5Si
M.W : 259.33
SMILES Code : C[Si](C)(C)CCOC(=O)ON1C(=O)CCC1=O
MDL No. :MFCD02683467
InChI Key :FLDNDAMSCINJDX-UHFFFAOYSA-N
Pubchem ID :5018386

Safety of [ 78269-85-9 ]

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

Computational Chemistry of [ 78269-85-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 0
Fraction Csp3 0.7
Num. rotatable bonds 6
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 65.91
TPSA ?

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

72.91 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.43
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

1.83
Log Po/w (WLOGP)?

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

1.16
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.

0.64
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

-0.57
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.1

Water Solubility

Log S (ESOL):?

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

-2.2
Solubility 1.62 mg/ml ; 0.00624 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.

-2.98
Solubility 0.271 mg/ml ; 0.00104 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

-1.61
Solubility 6.34 mg/ml ; 0.0244 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

Yes
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.

-6.58 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.

0.55

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

2.0 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<0.0
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)

3.02

Application In Synthesis of [ 78269-85-9 ]

* 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 [ 78269-85-9 ]

[ 78269-85-9 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 78269-85-9 ]
  • [ 7746-27-2 ]
  • 2-trimethylsilylethyl 6-bromo-3-methylindazole-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.44 g With sodium hydride; In 1,4-dioxane; at 1 - 40℃; for 2h; (3) Synthesis of 2-trimethylsilylethyl <strong>[7746-27-2]6-bromo-3-methylindazole</strong>-1-carboxylate [53-3] (hereinafter referred to as a compound [53-3]) To a solution of <strong>[7746-27-2]6-bromo-3-methyl-1H-indazole</strong> (1.0 g), which was obtained by the method described in the document (JP 2009-528363 W), in 1,4-dioxane (24 mL) were added sodium hydride (227 mg) and N-[2-(trimethylsilyl)ethoxycarbonyloxy]succinimide (1.84 g) at room temperature, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with water, and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (1.44 g) as a colorless oil. ESI-MS found: 355 [M + H]+
  • 2
  • [ 1240390-32-2 ]
  • [ 78269-85-9 ]
  • C11H23NO4Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In 1,4-dioxane; water; at 20℃; for 71h; A solution of <strong>[1240390-32-2](3S,4S)-3-aminotetrahydro-2H-pyran-4-ol</strong> (1, 2667 mg, 22.77 mmol) and triethylamine (4.76 mL, 34.15 mmol) in water (23 mL) and 1,4-dioxane (23 mL) was stirred at room temperature as 1-[(2-trimethylsilyl)ethoxycarbonyloxy]pyrrolidin-2,5-dione (2, 6498 mg, 25.06 mmol) was added. The resulting mixture was stirred at room temperature. After 71 h, the reaction mixture was diluted with water (125 mL) and extracted with ethyl acetate (125 mL×2). The extracts were washed with water (125 mL×1), combined, dried (Na2SO4) and concentrated. The residue was purified by column chromatography on silica gel (120 g column) using hexanes-ethyl acetate as eluents and the product containing fractions were pooled and concentrated to get compound 3: 1H NMR (400 MHz, Chloroform-d) δ 4.81 (s, 1H), 4.25-4.09 (m, 2H), 4.09-3.97 (m, 1H), 3.91 (dt, J=11.6, 4.7 Hz, 1H), 3.69 (s, 1H), 3.52 (d, J=9.5 Hz, 1H), 3.46 (ddd, J=11.9, 9.1, 3.1 Hz, 1H), 3.21 (t, J=9.4 Hz, 1H), 2.46 (s, 1H), 2.01 (dddd, J=13.1, 5.4, 4.4, 3.2 Hz, 1H), 1.65 (dtd, J=13.2, 8.8, 4.1 Hz, 1H), 1.07-0.90 (m, 2H), 0.04 (s, 9H). LCMS-ESI+ (m/z): [M+H-C2H4]+ calculated for C9H20NO4Si: 234.12. found: 233.94.
  • 3
  • [ 1159010-96-4 ]
  • [ 78269-85-9 ]
  • 2-trimethylsilylethyl 3-bromo-7,8-dihydro-5H-1,6-naphthyridine-6-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
400 mg With sodium carbonate; In tetrahydrofuran; at 25℃; for 5.0h; To a solution of 3-bromo-5,6,7,8-tetrahydro-1 ,6-naphthyridine hydrochloride (CAS:1159010-96-4, Vendor: PhamaBlock, 300 mg, 1.20 mmol), sodium carbonate (382 mg, 3.61 mmol) in THF (3 mL) and water (3 mL) was added N-[2- (trimethylsilyl)ethoxycarbonyloxyl succinimide (624 mg, 2.40 mmol). After being stirred at 25 C for 5 hrs, the reaction was quenched by addition of saturated NH4C1 (aq. 20 mL), diluted with 50 mL water, extracted with EA (30 mL) three times. The combined organic layer waswashed with water (30 mL) twice and brine (20 mL) once, dried over Na2SO4 and concentrated to give crude product which was purified by flash column (PE/EA = 10/1) to give compound 47a (400 mg) as a white solid. MS calc?d 357 (MHj, measured 357 (MHj.
  • 4
  • [ 78269-85-9 ]
  • [ 66866-69-1 ]
  • N-trimethylsilylethoxycarbonyl-N-methyl-L-leucine [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With sodium hydrogencarbonate; In water; acetone; at 25℃; (4) At 25C, in a 2L reaction flask equipped with a thermometer,Put 310mL acetone, 310mL water, 62.1g (0.34mol) in sequenceN-methyl-L-leucine hydrochloride,57.1g (0.68mol) sodium bicarbonate, 176.1g (0.68mol)N-[2-(Trimethylsilyl)ethoxycarbonyloxy]succinimide, stir and react overnight at 25C,Add 310mL water and 200mL petroleum ether, stir and extract,Separate the phases, adjust the aqueous phase to weak acidity with 3N hydrochloric acid, add 200mL ethyl acetate to extract the aqueous phase twice, combine the ethyl acetate phases, wash once with saturated sodium chloride, dry with anhydrous sodium sulfate, and concentrateObtain 86.8 g of N-trimethylsilyl ethoxycarbonyl-N-methyl-L-leucine, which is then recrystallized using ethyl acetate petroleum ether71.2g of N-trimethylsilylethoxycarbonyl-N-methyl-L-leucine was obtained, the yield was 72%, the chemical purity was 99.7%, and the chiral purity was 100%.
 

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