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Chemical Structure| 479353-60-1 Chemical Structure| 479353-60-1

Structure of 479353-60-1

Chemical Structure| 479353-60-1

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Product Details of [ 479353-60-1 ]

CAS No. :479353-60-1
Formula : C8H13ClNOP
M.W : 205.62
SMILES Code : CP(C)(C1=CC=C(N)C=C1)=O.[H]Cl
MDL No. :MFCD29922147
InChI Key :OAHOSYPEIKFMCS-UHFFFAOYSA-N
Pubchem ID :21897911

Safety of [ 479353-60-1 ]

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

Computational Chemistry of [ 479353-60-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 56.78
TPSA ?

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

52.9 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

1.06
Log Po/w (WLOGP)?

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

2.33
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.

1.44
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

1.06
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.18

Water Solubility

Log S (ESOL):?

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

-2.09
Solubility 1.68 mg/ml ; 0.00819 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.

-1.76
Solubility 3.56 mg/ml ; 0.0173 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

-2.82
Solubility 0.308 mg/ml ; 0.0015 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

Yes
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.

-6.8 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

2.0 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)

3.13

Application In Synthesis of [ 479353-60-1 ]

* 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 [ 479353-60-1 ]

[ 479353-60-1 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 479353-59-8 ]
  • [ 479353-60-1 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; H2;palladium; In ethanol; Step 3 4-(Dimethyl-phosphinoyl)-phenylamine hydrochloride A suspension of 1-(Dimethyl-phosphinoyl)-4-nitro-benzene (2.04 g, 10.2 mmol) and 10% palladium on carbon (0.411 g) in 103 mL of absolute EtOH containing 1.15 mL (11.4 mmol) of conc. HCl was flushed with H2 and stirred at ambient temperature (H2 balloon) for 2 h. The reaction mixture was filtered through Celite, the Celite washed with EtOH, and the combined filtrates concentrated to provide the crude product. Recrystallization from boiling iPrOH (10 mL) provided, after several crops, 1.17 g of an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ7.61 (dd, J=11.1, 8.4 Hz, 2H), 7.04 (dd, J=8.4, 2.0 Hz, 2H), 1.64 (s, 3H), 1.60 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ39.299.
With hydrogenchloride; H2;palladium; In ethanol; Step 3 4-(Dimethyl-phosphinoyl)-phenylamine Hydrochloride A suspension of 1-(Dimethyl-phosphinoyl)-4-nitro-benzene (2.04 g, 10.2 mmol) and 10% palladium on carbon (0.411 g) in 103 mL of absolute EtOH containing 1.15 mL (11.4 mmol) of conc. HCl was flushed with H2 and stirred at ambient temperature (H2 balloon) for 2 h. The reaction mixture was filtered through Celite, the Celite washed with EtOH, and the combined filtrates concentrated to provide the crude product. Recrystallization from boiling iPrOH (10 mL) provided, after several crops, 1.17 g of an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ 7.61 (dd, J=11.1, 8.4 Hz, 2H), 7.04 (dd, J=8.4, 2.0 Hz, 2H), 1.64 (s, 3H), 1.60 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ 39.299.
With hydrogenchloride; H2;palladium; In ethanol; Step 3 4-(Dimethyl-phosphinoyl)-phenylamine Hydrochloride A suspension of 1-(Dimethyl-phosphinoyl)-4-nitro-benzene (2.04 g, 10.2 mmol) and 10% palladium on carbon (0.411 g) in 103 mL of absolute EtOH containing 1.15 mL (11.4 mmol) of conc. HCl was flushed with H2 and stirred at ambient temperature (H2 balloon) for 2 h. The reaction mixture was filtered through Celite, the Celite washed with EtOH, and the combined filtrates concentrated to provide the crude product. Recrystallization from boiling iPrOH (10 mL) provided, after several crops, 1.17 g of an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ 7.61 (dd, J-=11.1, 8.4 Hz, 2H), 7.04 (dd, J=8.4, 2.0 Hz, 2H), 1.64 (s, 3H), 1.60 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ 39.299.
With hydrogenchloride; hydrogen;palladium 10% on activated carbon; In ethanol; at 20.0℃; for 2h; A suspension of 1-(Dimethyl-phosphinoyl)-4-nitro-benzene (2.04 g, 10.2 mmol) and 10% palladium on carbon (0.411 g) in 103 mL of absolute EtOH containing 1.15 mL (11.4 mmol) of cock. HCl was flushed with H2 and stirred at ambient temperature (H2 balloon) for 2 h. The reaction mixture was filtered through Celite, the Celite washed with EtOH, and the combined filtrates concentrated to provide the crude product. Recrystallization from boiling iPrOH (10 mL) provided, after several crops, 1.17 g of an off-white solid: 1H NMR (300 MHz, DMSO-d6) d 7.61 (dd, J=11.1, 8.4 Hz, 2H), 7.04 (dd, J=8.4, 2.0 Hz, 2H), 1.64 (s, 3H), 1.60 (s, 3H). 31P NMR (121 MHz, DMSO-d6) d 39.299.

  • 2
  • [ 956907-14-5 ]
  • [ 479353-60-1 ]
  • dimethyl(4-((1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)amino)phenyl)phosphine oxide [ No CAS ]
YieldReaction ConditionsOperation in experiment
15% 6-((6-Bromo- 1 H- [1,2,3 Itriazolo [4,5 -blpyrazine- 1-yl)methyl)-quinoline (2) (68 mg, 0.1993 mmol; CAS 956907-14-5), <strong>[479353-60-1](4-aminophenyl)dimethylphosphine oxide hydrochloride</strong> (31) (45 mg, 0.2192 mmol), Cs2CO3 (130 mg, 0.3986 mmol) and 5.5 mL of of 1,4-dioxane/H20 (10;1) were added to a 10 mL microwave reaction tube fitted with a magnetic stir bar and a septum. The reaction mixture was degassed by slowly bubbling N2 throughout the reaction mixture with stirring for 1 h.Pd2(dba)3 (18 mg, 0.0199 mmol) and Xantphos (23 mg, 0.0398 mmol) were added, the degassing continued for an additional 10 mm and then the reaction tube was placed on a CEM Discover microwave reactor at 120 C for 16 h. The reaction was cooled to room temperature and concentrated in vacuo. The residue was triturated with 3 times with 10 mL portions of a mixture of CH2CWMeOH (9:1). The combined triturations were concentratedin vacuo and the residue was purified by chromatography on silica gel eluting with a gradient of 0-15% MeOH in CH2C12 to furnish 13 mg (15%) of dimethyl(4-((1-(quinolin-6-ylmethyl)- 1H- [1,2,3 Itriazolo [4 ,5-blpyrazin-6-yl)amino)phenyl)phosphine oxide (30) as an off-white solid: MS (m/z) MH = 430; ‘H NMR (300 MHz, CD3OD): ö 8.85 (dd, J= 4.3, 1.6 Hz, 1H), 8.40 (broad d, J = 8.4 Hz, 1H), 8.31 (s, 1H), 8.09 (d, J = 1.6 Hz, 1H), 8.04 (d, J = 8.8 Hz,1H), 7.95-7.86 (m, 2H), 7.82, (dd, J= 8.8, 2.0 Hz, 1H), 7.70-7.60 (m, 2H), 7.57 (dd, J= 8.4,4.4 Hz, 1H), 6.07 (s, 2H), 1.78 (d, J= 13.4 Hz, 6H).
 

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