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Chemical Structure| 220641-87-2 Chemical Structure| 220641-87-2

Structure of 220641-87-2

Chemical Structure| 220641-87-2

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Product Details of [ 220641-87-2 ]

CAS No. :220641-87-2
Formula : C6H13NO
M.W : 115.17
SMILES Code : CNC1CCOCC1
MDL No. :MFCD06658492
InChI Key :WGYZZCUTSHNMET-UHFFFAOYSA-N
Pubchem ID :6991950

Safety of [ 220641-87-2 ]

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

Computational Chemistry of [ 220641-87-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 32.73
TPSA ?

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

21.26 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.85
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

0.2
Log Po/w (WLOGP)?

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

0.38
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.

0.21
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

1.1
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.75

Water Solubility

Log S (ESOL):?

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

-0.61
Solubility 28.0 mg/ml ; 0.243 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.

-0.21
Solubility 71.8 mg/ml ; 0.623 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

-1.16
Solubility 7.95 mg/ml ; 0.069 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.

-6.86 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.

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)

1.29

Application In Synthesis of [ 220641-87-2 ]

* 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 [ 220641-87-2 ]

[ 220641-87-2 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 220641-87-2 ]
  • [ 937046-98-5 ]
  • [ 51323-43-4 ]
  • 7-(3-((methyl(tetrahydro-2H-pyran-4-yl)amino)methyl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% To a suspension of N-methyltetrahydro-2H-pyran-4-amine (541 mg, 4.69 mmol) and <strong>[51323-43-4](3-(bromomethyl)phenyl)boronic acid</strong> (756 mg, 3.52 mmol) in acetonitrile (8 mL) was added K2C03 (973 mg, 7.04 mmol) under anhydrous conditions. After stirring at room temperature for 10 h, the reaction mixture was concentrated, phosphoric acid,potassium salt (1.50 g, 2.35 mmol), 7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine (500 mg, 2.347 mmol), dioxane (8 mL) and water (4 mL) were added. The reaction vessel was evacuated, backfilled with N2 and then degassed by bubbling N2 with sonication. Tetrakis triphenylphosphine (271 mg, 0.235 mol) was added and the degassing process was repeated. The resulting reaction mixture was heated at 140 C in a microwave for 45mm. The reaction complex was cooled, filtered, and washed with water. The filtrate was extracted with ethyl acetate (10 mL x 3). The organic layers were combined, dried and concentrated. The crude mixture was dissolved in DMF, and purified by preparative LC Method C to obtain 7-(3 -((methyl(tetrahydro-2H-pyran-4-yl)amino)methyl)phenyl) pyrrolo[2,1-f][1,2,4]triazin-4-amine, TFA (636 mg, 60% yield). LC/MS (M+H) =338.30.
  • 2
  • [ 220641-87-2 ]
  • 7-bromo-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine [ No CAS ]
  • [ 51323-43-4 ]
  • 7-(3-((methyl(tetrahydro-2H-pyran-4-yl)amino)methyl)phenyl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
41% N-Methyltetrahydro-2H-pyran-4-amine (19 mg,(bromomethyl)phenyl)boronic acid (23.60 mg, 0.111 mmol) were suspended in15 acetonitrile (2 mL). K2C03 (37.9 mg, 0.275 mmol) was added, then the reaction mixture was stirred at room temperature for lOh. The reaction mixture was concentrated, dioxane (1 mL) and water (0.5 mL), phosphoric acid, potassium salt (46.6 mg, 0.22 mmol) and 7- bromo-5 -(1 -(tetrahydro-2H-pyran-4-yl)- 1 H- 1,2,3 -triazol-5 -yl)pyrrolo[2, 1 -f] [1 ,2,4]triazin- 4-amine (20 mg, 0.055 mmol) (Intermediate Ri) were added to the residue. The reaction20 vessel was evacuated, backfilled with N2 and then degassed by bubbling N2 while being sonicated. Tetrakis triphenylphosphine (7 mg, 5.49 .imol) was added and the degassing process was repeated. The reaction mixture was heated at 140 C in a microwave for 45 mm. The reaction complex was filtered, washed with water and extracted with ethyl acetate (10 mL x 3). The organic layers were combined, dried and concentrated. The25 crude mixture was purified by preparative LC method C to provide 7-(3-((methyl (tetrahydro-2H-pyran-4-yl)amino)methyl)phenyl)-5 -(1 -(tetrahydro-2H-pyran-4-yl)- 1 H- 1 ,2,3-triazol-5-yl)pyrrolo[2, 1 -f] [1 ,2,4]triazin-4-amine (8.2 mg, 41% yield). LC/MS(M+H) = 489.30. ?HNMR(500 MHz, MeOD) 5 1.72 (m, 2H), 1.85 (m, 2H), 2.01 (m,2H), 2.29 (s, 3H), 2.42 (m, 2H), 2.75 (m, 1H), 3.42 (m, 2H), 3.47 (m, 2H), 3.73 (s, 2H),4.06 (m, 4H), 4.56 (m, 1H), 6.97 (s, 1H), 7.37 (d, 2H), 7.47 (t, 1H), 7.84 (s, 1H), 7.95 (m,2H), 8.01 (s, 1H).
 

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Technical Information

Categories

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