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Product Details of [ 2359-60-6 ]

CAS No. :2359-60-6
Formula : C11H16N2
M.W : 176.26
SMILES Code : NC1=CC=C(C=C1)N1CCCCC1
MDL No. :MFCD00051688
InChI Key :TVOSOIXYPHKEAR-UHFFFAOYSA-N
Pubchem ID :413501

Safety of [ 2359-60-6 ]

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

Computational Chemistry of [ 2359-60-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.45
Num. rotatable bonds 1
Num. H-bond acceptors 0.0
Num. H-bond donors 1.0
Molar Refractivity 60.3
TPSA ?

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

29.26 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.9
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

2.75
Log Po/w (WLOGP)?

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

1.89
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.

2.0
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

1.85
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.08

Water Solubility

Log S (ESOL):?

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

-2.94
Solubility 0.202 mg/ml ; 0.00115 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.

-3.02
Solubility 0.169 mg/ml ; 0.000956 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

-2.76
Solubility 0.306 mg/ml ; 0.00174 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.

-5.42 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

1.0
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.

2.0 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)

1.07

Application In Synthesis of [ 2359-60-6 ]

* 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 [ 2359-60-6 ]

[ 2359-60-6 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 6574-15-8 ]
  • [ 2359-60-6 ]
YieldReaction ConditionsOperation in experiment
100% With palladium on activated charcoal; hydrogen; In ethyl acetate; at 20℃; for 3h; 4-Fluoronitrobenzene (323 mg, 2.3 mmol) was dissolved in DMSO (5 ml), potassium carbonate (475 mg, 3.5 mmol) and piperidine (460 mul, 4.6 mmol) were added, and the mixture was stirred at 90 C. for 9 hr. Then, water was added to the reaction solution, and the mixture was extracted twice with ethyl acetate. The organic layer was washed twice with saturated aqueous NaCl. The organic layer was dried over Na2CO3, the solvent was evaporated to give compound Y197 (yield; 472 mg, 100%). Compound Y197 was dissolved in ethyl acetate (20 ml), Pd/C (186 mg) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature for 3 hr. Then, the reaction solution was filtered through celite, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (eluent; chloroform:methanol (40:1)) to give compound Y222 (yield, quantitative, 394 mg). Compound Y491 (mentioned later) (80 mg, 0.18 mmol) was dissolved in dichloromethane (2 ml), compound Y222 (100 mg, 0.58 mmol) was added, and the mixture was stirred at room temperature for 5 hr. Then, the solvent was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (eluent; chloroform:methanol (35:1)) to give the title compound (yield; 68 mg, 64%). 1H NMR (500 MHz, CDCl3) delta8.40 (s, 1H), 8.0 (d, 1H, J=8.0 Hz), 7.70 (d, 1H, J=8.5 Hz), 7.52 (dd, 1H, J=8.0, 7.5 Hz), 6.92 (dd, 2H, J=9.0, 3.5 Hz), 6.77 (dd, 2H, J=9.0, 6.5 Hz), 5.33 (t, 1H, J=6.0 Hz), 4.07 (bs, 2H), 3.11-3.09 (m, 4H), 2.79-2.64 (m, 4H), 1.69-1.53 (m, 10H), 1.43 (s, 9H), 1.09-1.01 (m, 2H) 13C NMR (125 MHz, CDCl3) delta154.9, 141.6, 140.8, 131.4, 130.9, 129.8, 125.8, 125.7, 79.7, 77.4, 48.7, 36.6, 29.6, 28.6, 25.7, 24.2 HRMS (FAB-) m/z: [M-H]- calcd for C28H39N4O6S2, 591.2311. found, 591.2324
99% With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; A suspension of 1.01 g (5 mmol) 1-bromo-4-nitrobenzene, 1.5 g K2CO3, 0.59 mL (6 mmol) piperidine in 10 mL of DMF was heated to reflux overnight. Upon cooling, the reaction mixture was dilute with water, extracted with EA, and the organic layer was washed with water, followed by saturated NaCl aqueous solution, dried over anhydrous Na2SO4 and purified by flash chromatography (PE : EA = 50:1, 30:1) to afford 902 mg (87%) yellow solid. The solid was dissolved in methanol, 90 mg Pd-C (10%) was added and stirred under hydrogen overnight at room temperature and then filtered through Celite and concentratedin vacuo. The crude product was purified by flash chromatography (PEEA = 5:1) to afford 4l? 0.706 g 99%.
96% Synthesis of 4-Piperidin-1-yl-phenylamine Ammonium chloride (228 mg, 4.2 mmol) in water (4 mL) was added to a solution of 1-(4-nitro-phenyl)-piperidine (220 mg, 1.0 mmol) in THF (6 mL) and the resulting mixture was stirred at 75 C. for 30 minutes. Iron powder (238 mg, 4.2 mmol) was then added portion wise and the mixture stirred for 5 hours at 75 C. The reaction mixture was filtered over celite, the filtrate was basified with sodium bicarbonate solution and the product extracted with ethyl acetate. The organic layer was washed with brine solution, dried over Na2SO4 and concentrated to afford 180 mg (96%) of 4-Piperidin-1-yl-phenylamine. LCMS: 177.13 (M+1)+, 80.6%, 1H NMR: (DMSO-d6): delta 6.67 (m, 2H), 6.47 (m, 2H), 4.51 (s, 2H), 2.57 (t, 4H), 1.6 (q, 4H), 1.49 (m, 2H)
85% With palladium 10% on activated carbon; hydrogen; In ethanol; at 20℃; for 23h; To a solution of <strong>[6574-15-8]1-(4-nitrophenyl)piperidine</strong> 15 (5.67 g, 0.028 mol) in EtOH (150 mL) was added 10%Pd/C (0.586 g, 10% w/w). The resulting mixture was stirred at roomtemperature under an atmosphere of hydrogen for 23 h. Aftercompletion, the mixture was filtered through Celite and washedwith EtOH. The solvent was removed in vacuo to afford a red oilwhich was extracted with DCM (3 x 10 mL) and washed with brine.The combined organic extracts were dried (MgSO4) and the solventwas removed in vacuo to give the title compound 18 (4.12 g, 85%) as ared oil which was used without further purification. deltaH (400 MHz;CDCl3) 1.51-1.57 (2H, m, H-40), 1.70-1.75 (4H, m, H-30), 3.00 (4H, t,J 5.5 Hz, H-20), 3.41 (2H, s, NH2), 6.63 (2H, d, J 8.8 Hz, H-2), 6.83(2H, d, J 8.8 Hz, H-3). deltaC (100 MHz; CDCl3) 24.2 (C-40), 26.2 (C-30),52.6 (C-20), 116.2 (C-2), 119.1 (C-3), 139.8 (C-1), 145.8 (C-4); IR numax(ATR)/cm-1: 3336, 2930, 2851, 1620, 1509, 1229, 819; m/z(ESI+): 259 (71%), 177 (100%); HRMS (ESI+) found (MH+): 177.1380,C11H17N2 requires 177.1386. The 1H NMR data were in agreementwith literature values [26].
80% With palladium 10% on activated carbon; hydrazine hydrate; In ethanol; for 12h;Reflux; The second step: to install a magnetic stir, thermometer, condenser 500mL three-necked flask is addedThe first step in the reaction of 15.0g of 4-nitrophenyl piperidine powder, 2.0g of 10% mass fraction of Pd / C,180mL of ethanol was added as a solvent, and stirred to obtain a uniform suspension. After heating to reflux, the suspensionWas slowly added dropwise 45.0g of mass fraction of 80% hydrazine hydrate solution, stirring continued at reflux for 12h. The reaction was completeCompleted, the reaction solution was filtered hot to remove Pd / C, the filtrate was concentrated under reduced pressure to 1/4 of its original volume, under a nitrogen atmosphereCooling and crystallization, to obtain a gray 4-aminophenyl-piperidine 10.2 g of crystals, 80% yield;
75% With palladium 10% on activated carbon; hydrazine hydrate; In ethanol; for 10h;Reflux; In a 500mL round-bottom flask, 28.3g (0.14mol) of nitro compound 1, 0.2g of 10 wt% Pd/C, 20mL hydrazine monohydrate and 180mL of ethanol was stirred at a reflux temperature for 10h. The solution was filtered hot to remove Pd/C, and the filtrate was evaporated under reduced pressure to dryness. A deep purplish red liquid was obtained. The product (2) was used for the next step without further purification. The yield was 18.1g (75%). IR (KBr): 3429, 3346cm-1 (-NH2 str.). 1H NMR (500MHz, DMSO-d6, delta, ppm): 6.66 (d, J=8.8Hz, 2H, He), 6.48 (d, J=8.8Hz, 2H, Hd), 4.49 (s, 2H, -NH2), 2.84 (t, J=5.4Hz, 4H, Hc), 1.59 (m, 4H, Hb), 1.45 (m, 2H, Ha). 13C NMR (125MHz, DMSO-d6, delta, ppm): 143.5 (C4), 141.9 (C7), 118.6 (C6), 114.7 (C5), 52.1 (C3), 25.8 (C2), 23.8 (C1)
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; 10% Palladium on carbon (0.05 g) was added to a solution of the nitroaniline (0.001 mol) in ethanol (50 mL) under a H2 (g) atmosphere (via balloon). The reaction mixture stirred at r. t. overnight and was then filtered through celite. The filtrate was concentrated to afford a dark yellow oil.
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; Step 2:; 10% Palladium on carbon (0.05 g) was added to a solution of the nitroaniline (0.001 mol) in ethanol (50 mL) under a H2 (g) atmosphere (via balloon). The reaction mixture stirred at r. t. overnight and was then filtered through celite. The filtrate was concentrated to afford a dark yellow oil.
384 mg With iron; ammonium chloride; In methanol; water; at 100℃; General procedure: The compound S1 (261 mg, 1.25 mmol), iron powder (210 mg, 4.76 mmol, 3 equiv.) and ammonium chloride (335 mg, 6.27 mmol, 5 equiv.) were dissolved in methanol : water (2 : 1, 15 mL). The reaction mixture was heated at 100 C overnight, cooled to RT, filtered through celite and the solvent was reduced under vacuum. The condensed mixture was extracted with DCM, washed with brine, dried with sodium sulfate and all solvent was evaporated to furnish the condensed residue, which was purified by flash chromatography (elution system - EA/Hexane = 1 : 1 ) to obtain the title compound (245 mg, 1.43 mmol).
With 5%-palladium/activated carbon; hydrogen; In ethanol; water; at 20℃; General procedure: The substituted nitro compound 11 (1 equiv in a mixture of EtOH-H2O, 95:5, 20mL) was treated with 10% Pd-carbon (5% w/w). The reaction was subjected to hydrogenation under hydrogen gas at room temperature and the reaction was monitored by TLC. After completion of the reaction, the mixture was filtered through a Celite bed and concentrated in a vacuum to afford product 12.
With FeO(OH)/C; hydrazine hydrate; In ethanol; at 0 - 80℃; for 4h; General procedure: To a solution of 1a (5 g, 22.5 mmol) in 95% ethanol (100 mL) wasadded goethite (FeO(OH))/C (1.0 g) at room temperature. And a solution of 80% hydrazine hydrate (25 mL, 400 mmol) in 95% ethanol (50 mL) was added dropwise to the mixture at 0 C. The reaction mixture was stirred at 80 C for 4 h. The solvent was removed in vacuo to give 2a (3.8 g, yield 74.5%). MS m/z: 278.2 [M+H]+.

  • 2
  • [ 1207-69-8 ]
  • [ 6574-15-8 ]
  • acridin-9-yl-[4-(piperidin-1-yl)phenyl]amine [ No CAS ]
  • [ 2359-60-6 ]
YieldReaction ConditionsOperation in experiment
6% Following the procedure outlined in Step 2 of Example 1, but substituting 4-piperidin-1-yl-1-nitrobenzene for 1-methyl-4-(4-nitrophenyl)piperazine, afforded 4-piperidin-1-ylaniline, which was reacted with 9-chloroacridine (according to Step 4 in the procedure of Example 1) to obtain the title compound with 6% overall yield. 1H NMR (CDCl3, 500 MHz): 8.05 (2H, m), 8.00 (2H, m), 7.48 (2H, m), 7.09 (4H, m), 6.86 (2H, m), 3.13 (4H, m), 1.71 (4H, m), 1.58 (2H, m); MS (ESI+TOF): 354 (M+)
  • 3
  • [ 2359-60-6 ]
  • [ 53554-29-3 ]
  • C18H22N4O3 [ No CAS ]
  • 4
  • [ 2359-60-6 ]
  • [ 76661-24-0 ]
  • 5-chloro-4-(3-nitrophenoxy)-N-(4-(piperidin-1-yl)phenyl)pyrimidin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
62.7% With trifluoroacetic acid; In iso-butanol; at 100℃; General procedure: To a solution of 3a-r (1.50 mmol, 1 eq) and 6a-b (1.50 mmol, 1eq) in 2-BuOH (8 mL) were added TFA (2 mL). The slurrywas heatedto 100 C for 2e3 h. The reaction mixture was allowed to cool toroom temperature and was neutralized with a saturated aqueoussodium bicarbonate solution. The mixture was then extracted withethyl acetate (50 mL) three times. The crude was purified by flashchromatography with 25:1 (v/v) dichloromethane - methanol.
 

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