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Chemical Structure| 42492-57-9 Chemical Structure| 42492-57-9
Chemical Structure| 42492-57-9

Boc-Sar-OMe

CAS No.: 42492-57-9

4.5 *For Research Use Only !

Cat. No.: A228164 Purity: 95%

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Product Details of [ 42492-57-9 ]

CAS No. :42492-57-9
Formula : C9H17NO4
M.W : 203.24
SMILES Code : O=C(OC)CN(C(OC(C)(C)C)=O)C
MDL No. :MFCD04973115
InChI Key :LTBDTYJYKRLTRN-UHFFFAOYSA-N
Pubchem ID :14018930

Safety of [ 42492-57-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 42492-57-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 0
Fraction Csp3 0.78
Num. rotatable bonds 6
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 51.27
TPSA ?

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

55.84 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.63
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

1.03
Log Po/w (WLOGP)?

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

1.03
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.

0.83
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

0.11
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.13

Water Solubility

Log S (ESOL):?

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

-1.35
Solubility 9.02 mg/ml ; 0.0444 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.

-1.79
Solubility 3.28 mg/ml ; 0.0161 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

-0.99
Solubility 20.8 mg/ml ; 0.102 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.

-6.81 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

1.0 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)

2.36

Application In Synthesis of [ 42492-57-9 ]

* 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.

  • Upstream synthesis route of [ 42492-57-9 ]

[ 42492-57-9 ] Synthesis Path-Upstream   1~12

  • 1
  • [ 24424-99-5 ]
  • [ 13515-93-0 ]
  • [ 42492-57-9 ]
YieldReaction ConditionsOperation in experiment
90% With triethylamine In dichloromethane at 0 - 20℃; for 48 h; Inert atmosphere To a suspension of sarcosine (35.64 g, 0.40 mol) in 350 mL MeOH was added thionyl chloride (29.02 mL, 0.40 mol) dropwise at 0 °C. After complete addition the cooling bath was removed and the reaction mixture was stirred for 30 min at r.t. and refluxed for further 6 h. The resulting solution was concentrated in vacuum and the residue was dried in high vacuum over night at r.t. to afford sarcosine methyl ester.HCl as a white powder which was used in the next step without further purification; yield: 56.14 g (quant.); mp. 102 °C. 1H-NMR (300 MHz, CDCl3): δ = 9.76 (s, 2 H, NH2), 3.88 (t, J = 5.6 Hz, 2 H, H-2), 3.82 (s, 3 H, H-4)), 2.83 (t, J = 5.2 Hz, 3 H, H-3). 13C-NMR(75 MHz, CDCl3): δ = 166.7 (C-1), 53.3 (C-2), 48.9 (C-3), 33.4 (C-4).1 To a suspension of sarcosine methylester.HCl (59.80 g, 0.43 mol) and (Boc)2O (138.01 mL, 0.65 mol) in 1.0 L CH2Cl2 TEA (119.09 mL, 0.86 mol) was added dropwise at 0 °C. After complete addition the cooling bath was removed and the reaction mixture was stirred for two days at r.t. Aq. HCl (1 M) was added until the aqueous layer showed pH = 6. The resulting two layers were separated and the organic layer was washed with dist. H2O, dried (Na2SO4), concentrated in vacuum and volatile impurities were removed in high vacuum over night at r.t. to afford a clear oil; yield: 78.65 g (90 percent)
References: [1] Synthesis (Germany), 2017, vol. 49, # 4, p. 770 - 774.
[2] Patent: EP1032561, 2004, B1, . Location in patent: Page 21.
  • 2
  • [ 186581-53-3 ]
  • [ 13734-36-6 ]
  • [ 42492-57-9 ]
YieldReaction ConditionsOperation in experiment
90% at 0℃; for 0.5 h; Boc-N-sarcosine methyl ester (18) was prepared by treating a solution of Boc-Sar- OH (1.0 g, 5.3 mmol) in 1 : 1 DCM/MeOH (25 mL) cooled to 0° C portionwise with diazomethane (2M solution, excess) until the reaction mixture turned slight yellow. The reaction was kept at 0° C for 30 min and then HOAc (2 drops) was added. The organic solvents were removed to afford 1.0 g (90percent) of 18.
References: [1] Patent: WO2008/145562, 2008, A1, . Location in patent: Page/Page column 40.
  • 3
  • [ 13734-36-6 ]
  • [ 74-88-4 ]
  • [ 42492-57-9 ]
References: [1] Organic Letters, 2018, vol. 20, # 19, p. 6003 - 6006.
[2] Tetrahedron, 2012, vol. 68, # 35, p. 7070 - 7076.
  • 4
  • [ 24424-99-5 ]
  • [ 74-88-4 ]
  • [ 42492-57-9 ]
YieldReaction ConditionsOperation in experiment
27%
Stage #1: With sodium hydrogencarbonate In tetrahydrofuran; water for 18 h;
Stage #2: With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5 h;
Stage #3: at 20℃; for 48 h;
Glycine methyl ester hydrochloride (50.0 g, 0.398 mol, 1 eq.) was added to a 1 L flask containing water (300 mL) and THF (200 mL). Sodium bicarbonate (37.8 g, 0.438 mol) was added portionwise, followed by di-tert-butyl dicarbonate (83.4 g, 0.382 mol). The reaction was stirred for 18 h, and then the separated organic phase was concentrated. The mixture was redissolved in EtOAC, washed with brine, dried over Na2SO4, and evaporated to give an oily product (72 g, 95percent). The oily product was dissolved in DMF (500 mL) and cooled to 0° C. To the mixture was added NaH (60percent, 18.3 g, 0.457 mol) portionwise. The mixture was then stirred for 30 min and MeI (81.1 g, 0.571 mol) was added at such a rate as to maintain a reaction temperature below 20° C. The mixture was stirred at RT for 48 h. The mixture was poured into ice water (1.5 L), extracted with MTBE (300 mL×2). The combined organics were washed with brine, dried over Na2SO4, and evaporated. Silica gel chromatography (PE:EtOAc 7:1) gave N-Boc-N-methyl glycine methyl ester (21 g, 27percent).
References: [1] Patent: US2015/72982, 2015, A1, . Location in patent: Paragraph 0195.
  • 5
  • [ 31954-27-5 ]
  • [ 74-88-4 ]
  • [ 42492-57-9 ]
References: [1] Journal of Organic Chemistry, 1988, vol. 53, # 3, p. 487 - 499.
  • 6
  • [ 13734-36-6 ]
  • [ 6674-22-2 ]
  • [ 74-88-4 ]
  • [ 42492-57-9 ]
References: [1] Patent: US5494925, 1996, A, .
[2] Patent: US5512576, 1996, A, .
[3] Patent: US5541168, 1996, A, .
[4] Patent: US5556909, 1996, A, .
[5] Patent: US5602154, 1997, A, .
  • 7
  • [ 4530-20-5 ]
  • [ 74-88-4 ]
  • [ 42492-57-9 ]
References: [1] Chemistry - A European Journal, 2010, vol. 16, # 39, p. 11954 - 11962.
[2] Journal of Natural Products, 2003, vol. 66, # 2, p. 183 - 199.
  • 8
  • [ 123-91-1 ]
  • [ 24424-99-5 ]
  • [ 5680-79-5 ]
  • [ 42492-57-9 ]
References: [1] Patent: US5747535, 1998, A, .
  • 9
  • [ 123-91-1 ]
  • [ 24424-99-5 ]
  • [ 5680-79-5 ]
  • [ 42492-57-9 ]
References: [1] Patent: EP739886, 1996, A2, .
  • 10
  • [ 614-45-9 ]
  • [ 31954-27-5 ]
  • [ 42492-57-9 ]
References: [1] Journal of the Chemical Society - Series Chemical Communications, 1991, # 20, p. 1475 - 1476.
  • 11
  • [ 24424-99-5 ]
  • [ 42492-57-9 ]
References: [1] Journal of Organic Chemistry, 1988, vol. 53, # 3, p. 487 - 499.
  • 12
  • [ 1070-19-5 ]
  • [ 13515-93-0 ]
  • [ 42492-57-9 ]
References: [1] Gazzetta Chimica Italiana, 1977, vol. 107, p. 381 - 385.
 

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