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Chemical Structure| 61655-77-4 Chemical Structure| 61655-77-4

Structure of 61655-77-4

Chemical Structure| 61655-77-4

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Product Details of [ 61655-77-4 ]

CAS No. :61655-77-4
Formula : C9H13ClN4
M.W : 212.68
SMILES Code : CN1CCN(C2=CN=CC(Cl)=N2)CC1
MDL No. :MFCD12024895
InChI Key :ZMVHGTJAFGHEBY-UHFFFAOYSA-N
Pubchem ID :9920770

Safety of [ 61655-77-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H319-H317
Precautionary Statements:P305+P351+P338-P280

Computational Chemistry of [ 61655-77-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.56
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 63.3
TPSA ?

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

32.26 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.18
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

1.01
Log Po/w (WLOGP)?

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

0.12
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.

0.38
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

1.11
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.96

Water Solubility

Log S (ESOL):?

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

-2.05
Solubility 1.91 mg/ml ; 0.00899 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.

-1.28
Solubility 11.2 mg/ml ; 0.0529 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

-2.44
Solubility 0.765 mg/ml ; 0.0036 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.

-6.88 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

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)

2.6

Application In Synthesis of [ 61655-77-4 ]

* 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 [ 61655-77-4 ]

[ 61655-77-4 ] Synthesis Path-Downstream   1~10

  • 2
  • [ 109-01-3 ]
  • [ 4774-14-5 ]
  • [ 61655-77-4 ]
YieldReaction ConditionsOperation in experiment
83% With triethylamine; In ethanol; for 1.25h;Reflux; General procedure: To a solution of absolute ethanol (5 mL) and dichlorodiazine (3.36 mmol) in a 50mL round-bottom flaskwas added triethylamine (5.03 mmol), followed by the amine (5.03 mmol). The mixture was stirred either under reflux of ethanol (for dichloropyridazine and for dichloropyrazine) or at room temperature (for dichloropyrimidines). The reaction was monitored by GC. Once the starting dichlorodiazinewas completely consumed, the mixture was poured into a saturated NH4Cl solution (20 mL), then extracted with CH2Cl2 (320 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated under vacuum. The crude solid was triturated in petroleum ether, filtered through a Buchner to afford the pure product.
80% In dichloromethane; Example 295-Cyano-furan-2-carboxylic acid [4-methyl-6.-(4-methyl-piperidin- 1 -yl)-3 ,4,5 ,6- tetrahydro-2H- [1,2'] -bipyrazinyl-5 -yl] -amide a) 6'-Chloro-4-methyl-3,4,5,6-tetrahydro-2H-[l,2']bipyrazinyl; To a solution of 2,6-dichloropyrazine (400 mg, 2.68 mmol) in 6 mL of CH2Cl2 was added 4-methylpiperidine (1.2 eq, 3.2 mmol) and allowed to stir overnight. The reaction was diluted with CH2Cl2 (50 mL) washed with H2O (2x50 mL) and dried (K2CO3) to give 450 mg (80%) of the title compound as a white solid. Mass spectrum (ESI, m/z): Calcd. for CnH15ClN2, 211.0 (M+H), found 211.1.
80% General procedure: To the N,N-dimethylformamide (DMF) (4 mL) solution of N,N-dimethylethylenediamine (95 mL, 0.87 mmol) was added K2CO3 (0.19 g, 1.3 mmol). After the reaction mixture was stirred at room temperature (RT) for 30 min, 2,6-dichloropyrazine (0.10 g, 0.67 mmol) was added and the resulting reaction mixture was further stirred at RT for 12 h. After removal of solvent in vacuo, the residue was treated with dichoromethane. Insoluble impurities were removed by filtration. Removal of solvent in vacuo gave the product 0.095 g in 71 % yield;
  • 3
  • [ 61655-77-4 ]
  • 6'-chloro-4-methyl-5'-nitro-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl [ No CAS ]
YieldReaction ConditionsOperation in experiment
8% With nitronium tetrafluoborate; In acetonitrile; at -50 - 0℃; for 0.5h; b) 6'-Chloro-4-methyl-5'-nitro-3,4,5,6-tetrahydro-2H-[l,2']bipyrazinyl; To a solution of 6'-chloro-4-methyl-3,4,5,6-tetrahydro-2H-[l,2']bipyridinyl (450 mg (2.12 mmol, as prepared in the previous step) in 7 mL of CH3CN was added NO2BF4 (198 mg, 1.48 mmol) in three portions. After 10 min, the reaction was cooled to the freezing point of -50 C and another 98 mg (0.73 mmol) Of NO2BF4 was added in one portion. The reaction was stirred for 20 min, warmed to 0 C, and placed in a freezer overnight. At this time the reaction was quenched with satd aq NaHCO3 (50 mL), extracted with EtOAc (2 x 20 mL), and dried (K2CO3). The EtOAc was removed in vacuo and the crude material was purified by preparative thin layer chromatography (20% EtOAc- hexane) to afford 42 mg (8%) of the title compound as a yellow solid.1H-NMR (CDCl3; 400 MHz): delta 7.65 (s, IH), 3.91-3.86 (m, 2H), 3.11-3.04 (m, 2H), 1.66-1.80 (m, 3H), 1.34- 1.24 (m, 2H), 1.01 (d, 3H, J = 6.4 Hz);
  • 4
  • [ 843662-48-6 ]
  • [ 61655-77-4 ]
  • [ 1006699-34-8 ]
  • 5
  • [ 754214-56-7 ]
  • [ 61655-77-4 ]
  • [ 1401731-62-1 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 100℃; for 12.33h;Inert atmosphere; Sealed tube; EXAMPLE 87: 5-(6-(4-methylpiperazin-l-yl)pyrazin-2-yl)-lH-pyrrolor2,3-b1pyridineThe starting material 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrrolo[2,3-b]pyridine (124) (50 mg, 0.2 mmol, 1 eq) and 2-chloro-6-(4-methylpiperazin-l-yl)pyrazine (63) (44 mg, 0.2 mmol, 1 eq) in DMF (5 mL) was degassed and purged under argon atmosphere for 10 min. To this reaction mixture was charged Cs2C03 (133 mg, 0.4 mmol, 2 eq) followed by addition of Pd(PPh3)4 (0.01 mg, 0.04 mmol) and degassing and purging under argon for an additional 10 min. The reaction mixture was heated at 100C for 12 h in a sealed tube. After completion of the reaction, the reaction mixture was diluted with CHC13 and filtered through Celite. The solvents were distilled off and the crude material was submitted for flash column purification in neutral alumina using 2% MeOH/CHCl3 to obtain pale yellow solid compound 5-(6-(4- methylpiperazin-l-yl)pyrazin-2-yl)-lH-pyrrolo[2,3-b]pyridine 125 in 20 mg quantity. The compound 125 was confirmed by 1HNMR and LCMS. 1H NMR (400 MHz, CDC13) delta: 8.96 (d, J=1.5Hz 1H), 8.55 (d, J=1.70Hz, 1H), 8.30 (s, 1H), 8.08 (s,lH), 7.35 (m, J=3.04, 1H), 6.60(m, J=1.95 1H), 3.75 (m, J=5.00, 4H), 2.58 (m, J=5.12, 4H), 2.38 (s , 3H); MS m/z 294.9 (M+H)+.
  • 6
  • [ 1111638-43-7 ]
  • [ 61655-77-4 ]
  • [ 1401732-32-8 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 100℃;Inert atmosphere; Sealed tube; Reaction Scheme 12EXAMPLE 43 : 1 -(4-methoxybenzyl)-3 -methyl-5 -(6-(4-methylpiperazin- 1 -yl)pyrazin-2- yP- 1 H-pyrazolo [3 ,4-b"|pyridineTo a stirred solution of 8 and 63 in 1,4 dioxane and water was added CS2CO3, the solution degassed, purged with nitrogen for 15 min, Pd(PPh3)4 was added and the reaction mass was again purged with nitrogen for another 15 min. The reaction mass was heated at 100C in a sealed tube overnight. After completion of the reaction the reaction mass was partitioned between ethyl acetate and water and the organic layer was separated and again extracted with ethyl acetate. The combined organic layer was dried over sodium sulphate and the solvent completely distilled off to get the crude. The crude was passed through 100-200 mesh silica gel eluting the pure compound at 70-80% ethyl acetate in hexane as off white coloured solid compound 64 (25 mg).
  • 7
  • [ 61655-77-4 ]
  • [ 620595-36-0 ]
  • 2-hydroxy-5-(6-(4-methylpiperazin-1-yl)pyrazin-2-yl)benzaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; ethanol; at 120℃; for 0.166667h;Microwave irradiation; General procedure: A microwave tube filled with compound 2 (0.35 mmol), alkoxy heteroaromatic chloride or amine heteroaromatic chloride (0.38 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.010 mmol), 2 M potassium carbonate (1.7 mmol) in dioxane : ethanol (2 : 3) was heated in the microwave reactor at power 100 W and 120 C for 10 min. After solvent was removed in vacuo, the residue was treated with ethyl acetate and washed with water. The obtained organic layer was dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography over silica gel.
  • 8
  • [ 61655-77-4 ]
  • [ 620595-36-0 ]
  • 5-(2-hydroxy-5-(6-(4-methylpiperazin-1-yl)pyrazin-2-yl)benzylidene)thiazolidine-2,4-dione [ No CAS ]
  • 9
  • [ 380151-86-0 ]
  • [ 61655-77-4 ]
  • 3-(6-(4-methylpiperazin-1-yl)pyrazin-2-yl)benzaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; ethanol; at 120℃; for 0.166667h;Microwave irradiation; General procedure: A microwave tube filled with compound 2 (0.35 mmol), alkoxy heteroaromatic chloride or amine heteroaromatic chloride (0.38 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.010 mmol), 2 M potassium carbonate (1.7 mmol) in dioxane : ethanol (2 : 3) was heated in the microwave reactor at power 100 W and 120 C for 10 min. After solvent was removed in vacuo, the residue was treated with ethyl acetate and washed with water. The obtained organic layer was dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography over silica gel.
  • 10
  • [ 380151-86-0 ]
  • [ 61655-77-4 ]
  • 5-(3-(6-(4-methylpiperazin-1-yl)pyrazin-2-yl)benzylidene)thiazolidine-2,4-dione [ No CAS ]
 

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