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Chemical Structure| 2524-67-6 Chemical Structure| 2524-67-6

Structure of 4-Morpholinoaniline
CAS No.: 2524-67-6

Chemical Structure| 2524-67-6

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Product Details of [ 2524-67-6 ]

CAS No. :2524-67-6
Formula : C10H14N2O
M.W : 178.23
SMILES Code : NC1=CC=C(N2CCOCC2)C=C1
MDL No. :MFCD00006169
InChI Key :PHNDZBFLOPIMSM-UHFFFAOYSA-N
Pubchem ID :75655

Safety of [ 2524-67-6 ]

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

Computational Chemistry of [ 2524-67-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.4
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 56.57
TPSA ?

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

38.49 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.71
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

0.68
Log Po/w (WLOGP)?

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

0.73
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

1.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.04

Water Solubility

Log S (ESOL):?

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

-1.65
Solubility 4.0 mg/ml ; 0.0224 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.

-1.07
Solubility 15.3 mg/ml ; 0.0861 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

-2.22
Solubility 1.07 mg/ml ; 0.006 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

Yes
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.

-6.9 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)

1.43

Application In Synthesis of [ 2524-67-6 ]

* 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 [ 2524-67-6 ]

[ 2524-67-6 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 2524-67-6 ]
  • [ 483324-01-2 ]
  • N-(4-morpholin-4-ylphenyl)-4-(pyridin-3-yl)pyrimidin-2-amine [ No CAS ]
  • 2
  • [ 464213-93-2 ]
  • [ 2524-67-6 ]
  • [ 37091-73-9 ]
  • N-[5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoyl]-4-morpholinoaniline [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; Example 110 N-[5-(5,6-Dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoyl]-4-morpholinoaniline 4-Morpholinoaniline (0.286 g, 1.60 mmol), triethylamine (0.162 g, 1.60 mmol) and <strong>[37091-73-9]2-chloro-1,3-dimethylimidazolinium chloride</strong> (0.271 g, 1.60 mmol) were added to a methylene chloride solution (20 ml) of 5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoic acid (0.200 g, 0.535 mmol) and the resulting solution was stirred at room temperature for 12 hours. The reaction solution was poured into ice water and then extracted with methylene chloride. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (hexane: ethyl acetate = 1:2) and then recrystallized from ether to obtain the titled compound (0.077 g, 0.144 mmol, 27percent).
  • 3
  • [ 2524-67-6 ]
  • [ 1030626-87-9 ]
  • [ 1030626-88-0 ]
YieldReaction ConditionsOperation in experiment
With 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 90℃; for 16.0h;Product distribution / selectivity; A.5 (5-Chloro-[l, 2, 4]triazolo[l, 5-a]pyridin-8-yl)-(4-morpholin-4-yl-phenyl)-amine[0332] A suspension of 8-bromo-5-chloro-[l,2,4]triazolo[l,5-a]pyridine (160 mg, 0.69 mmol),4-morpholin-4-yl-phenylamine (135 mg, 0.76 mmol), sodium-tert-butoxide (93 mg, 0.96 mmol), tris(dibenzylideneacetone)dipalladium (0) (13 mg, 13.76 mumol) and Xantphos (16 mg, 27.52 mumol) in dry toluene is heated at 90 0C in a sealed tube under a nitrogen atmosphere for 16 hours. The reaction mixture is evaporated to dryness and the residue partitioned between dichloromethane and 10 % aqueous citric acid. The organic phase is further washed with water (Ix) and brine (Ix), dried over magnesium sulfate, filtered and evaporated. The solid residue (207 mg) is purified by flash chromatography (silica gel, dichloromethane/methanol 97:3) affording the title compound (70 mg) as a solid.
  • 4
  • [ 2524-67-6 ]
  • [ 499195-60-7 ]
  • [ 1056634-62-8 ]
YieldReaction ConditionsOperation in experiment
88% With toluene-4-sulfonic acid; In 1,4-dioxane;Heating / reflux; A mixture of <strong>[499195-60-7]ethyl 4-(2-chloropyrimidin-4-yl)benzoate</strong> (26.15 g, 99.7 mmol) and 4-morpholinoaniline (23.10 g, 129.6 mmol) was suspended in 1,4-dioxane (250 mL). p- Toluenesulfonic acid monohydrate (17.07 g, 89.73 mmol) was added. The mixture was heated at reflux for 40 h., cooled to ambient temperature, concentrated then the residue was partitioned between ethyl acetate and 1 : 1 saturated sodium bicarbonate/water (IL total). The organic phase was washed with water (2 x 100 mL) and concentrated. The aqueous phase was extracted with dichloromethane (3 x 200 mL). The material which precipitated during this workup was collected by filtration and set aside. The liquid organics were combined, concentrated, triturated with methanol (200 mL) and filtered to yield additional yellow solid. The solids were combined, suspended in methanol (500 mL), allowed to stand overnight then sonicated and filtered. The solids were washed with methanol (2x 50 mL) to give, after drying, ethyl 4-(2-(4- morphonlinophenylamino)pyrimidin-4-yl)benzoate (35.39 g , 88%). 1H NMR (300 MHz, J6-DMSO) delta 9.49 (IH, s); 8.54 (IH, d, J= 5.0 Hz); 8.27 (2H, d, J= 8.7 Hz); 8.10 (2H, d, J= 8.7 Hz), 7.66 (2H, d, J= 9.1 Hz); 7.38 (IH, d, J= 5.0Hz); 6.93 (2H, d, J= 8.7 Hz); 4.35 (2H, q, J= 6.9 Hz), 3.73 (4H, m); 3.04 (4H, m); 1.34 (3H, t, J= 6.9 Hz); LC-ESI- MS (method B): rt 7.5 min.; m/z 404.1 [M+H]+.
  • 5
  • [ 2524-67-6 ]
  • [ 41360-32-1 ]
  • C18H20N2O5S [ No CAS ]
  • 6
  • [ 2524-67-6 ]
  • [ 160893-07-2 ]
  • 5-methoxy-N-(4-morpholinophenyl)quinolin-2-amine [ No CAS ]
  • 7
  • [ 2524-67-6 ]
  • [ 53554-29-3 ]
  • C17H20N4O4 [ No CAS ]
  • 8
  • [ 2524-67-6 ]
  • [ 76661-24-0 ]
  • 5-chloro-N-(4-morpholinophenyl)-4-(3-nitrophenoxy)pyrimidin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
80.4% 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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