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Chemical Structure| 6530-09-2 Chemical Structure| 6530-09-2

Structure of 6530-09-2

Chemical Structure| 6530-09-2

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Product Details of [ 6530-09-2 ]

CAS No. :6530-09-2
Formula : C7H16Cl2N2
M.W : 199.12
SMILES Code : NC1CN2CCC1CC2.[H]Cl.[H]Cl
MDL No. :MFCD00137395
InChI Key :STZHBULOYDCZET-UHFFFAOYSA-N
Pubchem ID :197853

Safety of [ 6530-09-2 ]

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

Computational Chemistry of [ 6530-09-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 54.98
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.

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

1.51
Log Po/w (WLOGP)?

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

1.26
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.

1.22
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

0.38
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.87

Water Solubility

Log S (ESOL):?

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

-2.03
Solubility 1.88 mg/ml ; 0.00942 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.

-1.73
Solubility 3.69 mg/ml ; 0.0185 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

-0.29
Solubility 101.0 mg/ml ; 0.508 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.

-6.44 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)

2.93

Application In Synthesis of [ 6530-09-2 ]

* 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 [ 6530-09-2 ]

[ 6530-09-2 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 704-91-6 ]
  • [ 6530-09-2 ]
  • [ 110-17-8 ]
  • N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-1H-indazole-6-carboxamide fumarate [ No CAS ]
  • 2
  • [ 478148-62-8 ]
  • [ 6530-09-2 ]
  • [ 478149-53-0 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; HATU; In DMF (N,N-dimethyl-formamide); at 0 - 20℃; for 2.5h; Acid C9 (1.96 g, 12.0 MMOL), DIEA (6.27 mL, 36.0 mmol), and R- (+)-3- aminoquinuclidine dihydrochloride (2. 42 g, 12.1 mmol) are added to DMF (60 mL), and the reaction is cooled in an ice bath. HATU (4.57 g, 12.0 mmol) is added, the solution allowed to warm to rt over 2.5 h, then CONCENTRATED IN VACUO. The residue is stirred with saturated NAHCO3 (30 mL) for 30 min, then extracted with CHC13 (10 X 50 mL). The combined organic layer is dried (NA2S04) and is concentrated in vacuo. The crude material is chromatographed over 130 g slurry-packed silica gel, eluting with 0.5% ammonium hydroxide in 10% MEOH/CHC13. The appropriate fractions are combined and concentrated to a residue.
  • 3
  • [ 6624-49-3 ]
  • [ 6530-09-2 ]
  • isoquinoline-3-carboxylic acid {(S)-1-azabicyclo[2.2.2]oct-2-yl}-amide monohydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
529 mg of <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> hydrate are dissolved in 18 mi of DMF, followed by addition of 508 mg of 1-hydroxy-benzotriazol and 1.81 G of dicyclohexyl-carbodiimide. After stirring for 1 h at r. t. , the precipitated dicylohexyl-urea is filtered off and 500 mg of 3 (S)- aminoquinuclidine dihydrochloride and 1.3 ml of ethyl-diisopropylamine is added to the filtrate. After stirring for 48 h at room temperature, a second portion of dicylohexyl-urea is filtered off and washed with MeOtBu/DMF (4: 1). Wash solution and filtrate are combined and crystallized by standing over night at 5° The crystalline precipitate is filtered off and washed with MeOtBu/DMF (4: 1), followed by MeOtBu to yield the title compound as monohydrochloride. NMR (1H, 400 MHz, AH d6-DMSO) : 1.75 (1H, t), 1.96 (2H, m), 2.12 (1H, q), 2.24 (1H, d), 3.24 (3H, m), 3.43 (2H, m), 3.65 (1'H, t), 4.49 (1H, q), 7. 86 (1H, t), 7.92 (1H, t), 8. 24 (1H, d), 8.30 (1H, d), 8. 61 (1H, s), 9.31 (1 H, d), 9. 46 (1H, s), 10.59 1H, br). MS (ES+) : 282 (MH)+
  • 4
  • [ 77837-08-2 ]
  • [ 6530-09-2 ]
  • [ 1392219-90-7 ]
YieldReaction ConditionsOperation in experiment
70% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In acetonitrile; at 20℃; for 24h; General procedure: Method 3: [0050] After 300 mg (1.39 mmol) of <strong>[77837-08-2]6-oxo-1-phenyl-1,6-dihydro-3-pyridinecarboxylic acid</strong> was dissolved in 10 mL of acetonitrile, 415 mg (2.08 mmol) of 3-aminoquinuclidine dihydrochloride and 718 mg (5.56 mmol) of diethylisopropylamide were added to the solution. Afterward, 207 mg (1.53 mmol) of 1-hydroxylbenzotriazole (HOBt) and 266 mg (1.39 mmol) of N-(3-dimethylaminopropyl)-N?-ethylcarbodiimide hydrochloride (EDC) were added to the reaction solution. This reaction solution was stirred at room temperature for about 24 hours. After termination of the reaction was determined by liquid chromatography, the solvent was removed in vacuo and then extracted three times with chloroform and an aqueous NaOH solution (pH=12), followed by purification using liquid chromatography (chloroform:methanol: ammonia water=10:1:0.1) to obtain a target compound (Actual yield: 317 mg, Percent yield: 70percent). [0051] 1H-NMR (CDCl3,200 MHz) delta8.11 (s, 1H), 7.75 (d, 1H), 7.40 (m, 4H), 6.65 (d, 1H), 6.26 (br, 1H), 4.15 (m, 1H), 3.39 (m, 1H), 2.89 (m, 4H), 2.53 (m, 1H), 2.06 (m, 1H), 1.53 (m, 4H)
 

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Technical Information

Categories

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