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Chemical Structure| 76003-29-7 Chemical Structure| 76003-29-7

Structure of 4-Boc-2-Oxopiperazine
CAS No.: 76003-29-7

Chemical Structure| 76003-29-7

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Product Details of [ 76003-29-7 ]

CAS No. :76003-29-7
Formula : C9H16N2O3
M.W : 200.23
SMILES Code : CC(OC(=O)N1CC(=O)NCC1)(C)C
MDL No. :MFCD02181069
InChI Key :FCMLWBBLOASUSO-UHFFFAOYSA-N
Pubchem ID :3157178

Safety of [ 76003-29-7 ]

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

Computational Chemistry of [ 76003-29-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 0
Fraction Csp3 0.78
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 58.7
TPSA ?

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

58.64 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.01
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

0.23
Log Po/w (WLOGP)?

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

-0.41
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.

0.03
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

0.24
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.42

Water Solubility

Log S (ESOL):?

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

-1.03
Solubility 18.8 mg/ml ; 0.0937 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.

-1.02
Solubility 19.1 mg/ml ; 0.0952 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

-1.17
Solubility 13.5 mg/ml ; 0.0675 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.

-7.36 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

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)

2.15

Application In Synthesis of [ 76003-29-7 ]

* 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 [ 76003-29-7 ]

[ 76003-29-7 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 76003-29-7 ]
  • [ 175205-81-9 ]
  • [ 1154868-68-4 ]
YieldReaction ConditionsOperation in experiment
92% Step 1: ferf-Butyl 3-oxo-4-r4-(trifluoromethyl)pyridin-2-yllpiperazine-l-carboxylate (II)A mixture of l-Boc-3-oxopiperazine (1.0 eq.), <strong>[175205-81-9]2-bromo-4-(trifluoromethyl)pyridine</strong> (1.5 eq.) and Cs2CO3 (1.5 eq.) in 1,4-dioxane (0.5M) was degassed under Argon flow for 30 min, then Pd(OAc)2 (0.1 eq.) and Xantphos (0.15 eq.) were added, the vial was sealed and stirring was continued at 1100C for 18 hr. Reaction mixture was diluted with EtOAc and filtered through a pad of SolcaFloc.(R). 200 FCC. After removal of the solvent, the crude product was purified by flash column chromatography on silica gel using 10- 40percent EtO Ac/Petroleum ether as eluent to afford the desired product Il as yellow solid (92percent yield). 1R NMR (400 MHz, CDCl3, 300K) delta 8.57 (IH, d, J = 4.8 Hz), 8.40 (IH, bs), 7.32 (IH, d, J = 4.8 Hz), 4.31 (2H, s), 4.17 (2H, t, J = 5.3 Hz), 3.76 (2H, t, J = 5.3 Hz), 1.50 (9H, s). MS (ES) Ci5Hi8F3N3 O3 requires: 345, found: 346 (M+H)+.
  • 2
  • [ 192702-01-5 ]
  • [ 76003-29-7 ]
  • [ 851726-46-0 ]
YieldReaction ConditionsOperation in experiment
To a cold (0 C) suspension of tert-butyl 3-oxopiperazine-1-carboxylate (2.0 g, 9.99 mmol) in DMF (20 mL) under an atmosphere of nitrogen, a solution of lithium bis (trimethylsilyl) amide in THE (10.69 mL, 10.69 mmol) was added and stirred at the temperature for 30 min. The resultant clear red brown solution was treated with <strong>[192702-01-5]3-chloro-4-fluorobenzyl bromide</strong> (2.34 mL, 10.49 mmol), and stirred at 0 C for 2 hours. The product mixture was concentrated under vacuum, and the residue partitioned between water and ethyl acetate. The organic extract was washed successively with 5% aq KHS04, sat. NaHC03, and brine. The organic fraction was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a 0-100% gradient of ethyl acetate in hexane. Collection and concentration of appropriate fractions provided the benzylated product. 'H NMR (400 MHz, CDC13) 8 7.32 (dd, J = 6.7, 1. 8 Hz, 1H), 7. 17-7. 09 (m, 2H), 4.55 (s, 2H), 4.16 (s, 2H), 3.61 (t, J = 5.3 Hz, 2H), 3.27 (t, J = 5.3 Hz, 2H), 1.47 (s, 9H).
  • 3
  • [ 76003-29-7 ]
  • [ 645-36-3 ]
  • [ 345311-03-7 ]
YieldReaction ConditionsOperation in experiment
With tin(IV) chloride; In 1,3,5-trimethyl-benzene;Reflux; EXAMPLE E; Preparation of Compounds E of Formula 1 ^N^s^ Br+ General Process for the Preparation of Compound E-In-2 from E-In- 1 :[00127] A round bottom flask was charged with E-In-I (1 eq.), CH2CI2, mesitylene and Tin(IV) chloride (0.3 eq.). The mixture was brought to reflux then aminoacetaldehyde diethyl acetal (2 eq.) was added slowly. The reaction was refluxed for 2 - 3d. The reaction was diluted with CH2CI2 and filtered through activated charcoal and the filtrate was evaporated giving a solid which was purified by trituration, or recrystallization, or silica gel column chromatography, or Shimadzu automated preparative HPLC system, to afford E-In-2.
  • 4
  • [ 76003-29-7 ]
  • [ 549506-47-0 ]
  • 5
  • [ 76003-29-7 ]
  • [ 156001-49-9 ]
  • tert-butyl 4-(4-bromo-2-methylbenzyl)-3-oxopiperazine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% [0654j To a solution of tert-butyl 3 -oxopiperazine- 1 -carboxylate (1.2 g, 6.0 mmol) in THF (200 mL) was added NaH (320 mg, 8.1 mmol) with ice-bath cooling. After stirring at 0 C for 1 h, a solution of <strong>[156001-49-9]4-bromo-1-(bromomethyl)-2-methylbenzene</strong> (1.42 g, 5.4 mmol) in THF (5 mL) was added dropwise over a period of 10 mm, the ice-bath was removed and the mixture was stirred at rt for 2 h. The mixture was diluted with ice-water (50 mL) and extracted with EtOAc (100 mL x 2) and the combined organic phases were washed with brine (50 mL), dried (Na2SO4) and concentrated in vacuo to afford a residue which was purified by silica gel column (petroleum ether/EtOAc = 5:1) to give tert-butyl 4-(4-bromo-2-methylbenzyl)-3-oxopiperazine- 1- carboxylate (1.6 g, yield: 77%) as white solid. ESI-MS (M+H-56) : 327.0. ?H NMR (400 MHz, CDC13) 5: 7.34 (s, 1H), 7.30 (d, J= 8.4 Hz, 1H), 6.99 (d, J= 8.4 Hz, 1H), 4.61 (s, 2H), 4.16 (s, 2H), 3.60 (t,J= 5.2 Hz, 2H), 3.24 (t,J= 5.2 Hz, 2H), 2.27 (s, 3H), 1.47 (s, 9H).
 

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