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Structure of 144222-22-0

Chemical Structure| 144222-22-0

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Product Details of [ 144222-22-0 ]

CAS No. :144222-22-0
Formula : C11H22N2O2
M.W : 214.30
SMILES Code : NCC1CCN(C(OC(C)(C)C)=O)CC1
MDL No. :MFCD01076207
InChI Key :KLKBCNDBOVRQIJ-UHFFFAOYSA-N
Pubchem ID :736817

Safety of [ 144222-22-0 ]

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

Computational Chemistry of [ 144222-22-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 0
Fraction Csp3 0.91
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 64.11
TPSA ?

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

55.56 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.65
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

0.92
Log Po/w (WLOGP)?

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

1.21
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.

1.15
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

0.69
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.33

Water Solubility

Log S (ESOL):?

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

-1.48
Solubility 7.03 mg/ml ; 0.0328 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.

-1.67
Solubility 4.55 mg/ml ; 0.0212 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

-1.33
Solubility 10.1 mg/ml ; 0.0471 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.

-6.95 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)

2.17

Application In Synthesis of [ 144222-22-0 ]

* 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 [ 144222-22-0 ]

[ 144222-22-0 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 38871-41-9 ]
  • [ 144222-22-0 ]
  • [ 261767-14-0 ]
  • 2
  • [ 31872-62-5 ]
  • [ 144222-22-0 ]
  • [ 173604-55-2 ]
YieldReaction ConditionsOperation in experiment
100% In methanol; for 2h;Heating / reflux; [0538] A solution of 643 mg (3.00 mmol) tert. butyl-4-aminomethyl-piperidin-1-carboxylate and 471 mg (3.00 mmol) <strong>[31872-62-5]4-methoxy-3-nitro-pyridine</strong> in 5 mL MeOH was refluxed for 2 hours and then evaporated down i. vac. The crude product was purified by column chromatography (silica gel, gradient dichloromethane/MeOH 100:0-->19:1 v/v) (Yield: 1.010 g, quantitative). [0539] The intermediate product was added to a suspension of 500 mg Raney nickel in 30 mL MeOH and the mixture was hydrogenated for 6 hours at 50° C. and 50 psi H2-pressure. The catalyst was filtered off and the filtrate evaporated i. vac. The crude product was purified by column chromatography (Alox (neutral, activity II-III), Gradient dichloromethane/MeOH 99:1-->19:1 v/v) purified. [0540] Yield: 0.480 g (53percent of theory) [0541] Rf=0.15 (silica gel, dichloromethane/MeOH 19/1 v/v) [0542] ESI-MS: (M+H)+=307
  • 3
  • [ 389602-62-4 ]
  • [ 68957-94-8 ]
  • [ 144222-22-0 ]
  • [ 389601-23-4 ]
YieldReaction ConditionsOperation in experiment
38% With 4-methyl-morpholine; In dichloromethane; EXAMPLE 18 N-(N-tert.butoxycarbonyl-piperidin-4-yl-methyl)-3-(4'-trifluoromethylbiphenyl-2-carbonylamino)-benzoic acid amide Prepared analogously to Example 7 from 3-(4'-trifluoromethylbiphenyl-2-carbonylamino)-benzoic acid and N-tert.butoxy-carbonyl-piperidin-4-yl-methylamine in dichloromethane with the addition of propanephosphonic acid cycloanhydride and N-methylmorpholine. Yield:38% of theory Rf value:0.68 (silica gel; dichloromethane/ethanol=9:1)
  • 4
  • [ 17794-48-8 ]
  • [ 80029-43-2 ]
  • [ 144222-22-0 ]
  • 1-(tert-butoxycarbonyl)-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With triethylamine; In dichloromethane; water; Reference Example 29 Preparation of 1-(tert-Butoxycarbonyl)-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine N-{3-(Trifluoromethyl)benzoyl}glycine (4.22 g, 17.0 mmol), EDCI (4.25 g, 22.1 mmol), 1-hydroxybenzotriazole hydrate (2.99 g, 22.1 mmol) and Et3N (1.72 g) were added to a solution of 1-(tert-butoxycarbonyl)-4-(aminomethyl)piperidine (4.03 g) in dry CH2Cl2 (200 mL). The reaction mixture was stirred at 25 C. for 20 h. H2O (100 mL) was added to the reaction mixture and the mixture was extracted with CH2Cl2 (2*50 mL). The combined extracts were washed with H2O (2*50 mL), brine (50 mL) and dried (MgSO4). The solvent was removed under reduced pressure to afford an yellow oil which was purified by column chromatography (SiO2, 70% EtOAc-hexane) to give 1-(tert-butoxycarbonyl)-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine as a white solid (6.39 g, 85%): 1H-NMR (CDCl3, 300 MHz) delta1.4 (s, 9H), 1.0-1.8 (m, 5H), 2.6-2.8 (m, 2H), 3.15-3.3 (m, 2H), 4.0-4.3 (m, 4H), 6.6-6.7 (m, 1H), 7.64 (s, 1H), 7.60 (dd, 1H, J=7.2, 7,2 Hz), 7.79 (d, 1H, J=7,2 Hz), 8.0 (d, 1H, J=7.2 Hz), 8.11 (s, 1H); The purity was determined by RPLc/MS (97); ESI/MS m/e 444.3 (M++H, C21H28F3N3O4).
85% With triethylamine; In dichloromethane; water; [Reference Example 29] Synthesis of 1-(tert-butoxycarbonyl)-4-[[N-(3-(trifluoromethyl)benzoyl)glycyl]aminomethyl]piperidine N-[3-(Trifluoromethyl)benzoyl]glycine (4.22 g, 17.0 mmol), EDCI (4.25 g, 22.1 mmol), 1-hydroxybenzotriazole hydrate (2.99 g, 22.1 mmol) and triethylamine (1.72 g) were added to an anhydrous dichloromethane (200 mL) solution of 1-(tert-butoxycarbonyl)-4-(aminomethyl)piperidine (4.03 g). The resulting reaction mixture was stirred at 25 C for 20 hours, and H2O (100 mL) was then added to the mixture. The obtained mixture was extracted with dichloromethane (50 mL * 2). The extracts were combined, washed with H2O (50 mL * 2) and brine (50 mL), dried (over MgSO4) and concentrated to thereby afford a yellow oil. The obtained crude product was purified by column chromatography (SiO2,70% ethyl acetate-hexane) to provide 1-(tert-butoxycarbonyl)-4-[[N-(3-(trifluoromethyl)benzoyl)glycyl]aminomethyl]piperidine as a white solid (6.39 g, 85%). 1H NMR(CDCl3, 300MHz) delta 1.4 (s, 9H), 1.0-1.8 (m, 5H), 2.6-2.8 (m, 2H), 3.15-3.3 (m, 2H), 4.0-4.3 (m, 4H), 6.6-6.7 (m, 1H), 7.64 (s, 1H), 7.60 (dd, 1H, J = 7.2, 7.2 Hz), 7.79 (d, 1H, J = 7.2 Hz), 8.0 (d, 1H, J = 7.2 Hz), 8.11 (s, 1H). The purity was determined by RPLC/MS (97%). ESI/MS m/e 444.3 (M++H, C21H28N3O4).
  • 5
  • [ 1071017-49-6 ]
  • [ 144222-22-0 ]
  • [ 1071017-71-4 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In 1,4-dioxane; water; at 100℃; for 48h; 4-[(3-Pyhdin-4-yl-[2, 6]naphthyridin- 1 -ylamino) -methylj-piperidine- 1 -carboxylic acid tert-butyl ester.; To a solution of 1-chloro-3-pyridin-4-yl-[2,6]naphthyridine (50.0 mg, 0.197 mmol) in 1 ,4- dioxane (5 ml_) is added 4-aminomethyl-piperidine-1 -carboxylic acid fert-butyl ester (128 mg, 0.590 mmol) and 40% aqueous NaOH (29.0 μl_, 0.290 mmol) at rt. The reaction mixture is heated to 1000C for 48 h, and then cooled to rt, diluted with EtOAc and filtered through a Florisil plug. The filtrate is evaporated to dryness to yield the title compound as a yellow oil, which is used without further purification for the next step.
  • 6
  • [ 1137475-57-0 ]
  • [ 144222-22-0 ]
  • [ 1137475-56-9 ]
YieldReaction ConditionsOperation in experiment
98% With triethylamine; In acetonitrile; for 0.516667h; A solution of 4-(aminomethyl)-1-boc-pipeiotadine (370 mg, 1.73 mmol) in acetonitrile (1 ml_) was added over 1 minute to a solution of <strong>[1137475-57-0]2-bromo-4-chloro-5-nitropyridine</strong> (373 mg, 1.57 mmol) and triethylamine (0.24 mL, 1.73 mmol) in acetonitrile (5 mL). The solution was stirred for 30 minutes then partitioned between dichloromethane and water. The aqueous phase was extracted with dichloromethane (x3) and the combined organic phases were dried (Na2SO4) and concentrated to give tert-butyl 4-((2-bromo-5-nitropyridin-4- ylamino)methyl)piperidine-1-carboxylate as a light brown foam (640 mg, 98%) which was used without further purification.1H NMR (MeOD, 400MHz) delta 8.82 (s, 1 H), 7.25 (s, 1 H), 4.14 (m, 3H), 3.35 (s, 1H), 1.97- 1.88 (m, 1H), 1.80 (m, 3H), 1.27-1.17 (m, 3H). LCMS (1) Rt = 2.35 min; m/z (ESI+) 415, 417 (MH+).
  • 7
  • [ 7579-20-6 ]
  • [ 144222-22-0 ]
  • [ 1237526-05-4 ]
  • 8
  • [ 1137475-57-0 ]
  • [ 144222-22-0 ]
  • [ 1351533-49-7 ]
  • 9
  • [ 42926-52-3 ]
  • [ 1341104-70-8 ]
  • [ 144222-22-0 ]
  • [ 1414263-88-9 ]
  • 10
  • [ 475216-25-2 ]
  • [ 144222-22-0 ]
  • C19H28N4O5 [ No CAS ]
 

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Technical Information

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