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Chemical Structure| 7153-13-1 Chemical Structure| 7153-13-1

Structure of 7153-13-1

Chemical Structure| 7153-13-1

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Product Details of [ 7153-13-1 ]

CAS No. :7153-13-1
Formula : C5H5Cl2N3
M.W : 178.02
SMILES Code : CC1=C(N=C(N)N=C1Cl)Cl
MDL No. :MFCD00023253
InChI Key :ISVBZKXYQWWVPC-UHFFFAOYSA-N
Pubchem ID :246751

Safety of [ 7153-13-1 ]

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

Computational Chemistry of [ 7153-13-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.2
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 41.42
TPSA ?

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

51.8 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.67
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

2.14
Log Po/w (WLOGP)?

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

1.68
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.

0.95
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

1.96
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.68

Water Solubility

Log S (ESOL):?

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

-2.74
Solubility 0.327 mg/ml ; 0.00184 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.

-2.86
Solubility 0.246 mg/ml ; 0.00138 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

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

-2.91
Solubility 0.219 mg/ml ; 0.00123 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.

-5.87 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)

1.69

Application In Synthesis of [ 7153-13-1 ]

* 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.

  • Upstream synthesis route of [ 7153-13-1 ]
  • Downstream synthetic route of [ 7153-13-1 ]

[ 7153-13-1 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 1395342-96-7 ]
  • [ 7153-13-1 ]
YieldReaction ConditionsOperation in experiment
96% With hydrogenchloride; water In ethanol at 50℃; for 2 h; Substituted 4,6-dichloro-2-[(dimethylamino)methylene]amino}pyrimidines were subjected to deprotextion of the (dimethylamino)methylene protecting group from the amino group in position 2 of the pyrimidine ring. For this reaction, the method described in the literature [Nucleosides, Nucleotides Nucleic Acids 19(1 a2), 297-327, 2000] was used, innovatively modified in order to make it possible to merely filter the product from the reaction mixture. A flask was filled with 50 mmol of substituted 4,6-dichloro-2- [(dimethylamino)methylene] amino} -pyrimidine, 200 ml of 99percent ethanol and 20 ml of resultant HC1. The reaction mixture was subsequently warmed up to 50 °C for two hours, during which a crystalline product began to separate directly from the reaction mixture. After that, 300 ml of water were added and the reaction mixture was intensively stirred for 10 minutes while quantitatively yielding the desired product, which was subsequently sucked off and rinsed with 2x 50 ml of a water/ethanol mixture (1/1), lx 5percent NaHC0&3 aqueous solution and lx 50 ml of a water/ethanol mixture (1/1). The product was subsequently recrystallized in 99percent ethanol. After complete cooling to 0 °C, the separated white crystals were sucked off, rinsed with lx 50 ml of a water/ethanol mixture (1/1) and dried in a vacuum drier.2-amino-4,6-dichloro-5-methylpyrimidine (25)Yield: 8.53 g (96 percent of the theor. yield); m.p. 189-190 °C. NMR (DMSO-6): 7.26 bs, 2H, (NH2); 2.17 s, 3H, (Η-1'). 13C NMR (DMSO-6): 161.01 (C-4 and 6); 160.78 (C-2); 1 13.60 (C-5); 14.93 (C-Γ). For C5H5C12N3: calculated: 33.73 percent C, 2.83 percent H, 39.83 percent CI, 23.60 percent N; found: 33.53 percent C, 2.78 percent H, 40.02 percent CI, 23.42 percent N. MS (EI), m/z (percent): 177 and 179 [M+] (100). MS (ESI+), m/z (percent): 178 and 180 [M+H+] (100).
1.26 g With hydrogenchloride In ethanol; water at 50℃; for 2 h; General procedure: Prior to the reaction, the starting 5-substituted 2-amino-4,6-dihydroxypyrimidine A2–A11 was dried in a vacuum drier at 80 °C and under 0.1 mbar for 1 day, because crystalline water increases the amount of the Vilsmeier–Haack–Arnold reagent required for full conversion. Subsequently, 5-substituted 2-amino-4,6-dihydroxypyrimidine (10 mmol) was suspended under inert atmosphere in a 2 M solution of the Vilsmeier–Haack–Arnold reagent (80 mmol, 40 mL) in chloroform. The reaction mixture was subsequently heated at reflux for 4 h, during which the starting material was completely dissolved. The reaction mixture was cooled to the room temperature, poured onto ice and rapidly neutralized with a saturated aqueous NaHCO3 solution. The obtained mixture was quickly transferred into a separatory funnel and immediately extracted with chloroform(3 x 20 mL). The organic fractions were combined together,dried over MgSO4, filtered through a 0.5 cm layer of silica gel and concentrated down on a rotary evaporator. This crude residue of 5-substituted 4,6-dichloro-2-[(dimethylamino)methylene]amino}pyrimidine was dissolved in the mixture of 99 percent ethanol (20 mL) and 37 percentaqueous HCl (2 mL). The reaction mixture was heated at 50 °C for 2 h, during which a crystalline product began to precipitate directly from the reaction mixture. After that, water (30 mL) was added and the reaction mixture was intensively stirred for 10 min. The precipitated product was filtered off and washed with a water/ethanol mixture (1/1,2 x 10 mL), 5 percent aqueous solution of NaHCO3 (10 mL) and a water/ethanol mixture (1/1, 10 mL). The product was subsequently recrystallized from aqueous ethanol, filtered off, washed with a water/ethanol mixture (1/1, 10 mL) and dried under high vacuum.
References: [1] Patent: WO2012/116666, 2012, A1, . Location in patent: Page/Page column 38-39.
[2] Medicinal Chemistry Research, 2014, vol. 23, # 10, p. 4482 - 4490.
[3] Medicinal Chemistry Research, 2014, vol. 23, # 10, p. 4482 - 4490.
  • 2
  • [ 6627-65-2 ]
  • [ 7153-13-1 ]
References: [1] Patent: US2004/204386, 2004, A1, .
[2] Journal of Medicinal Chemistry, 2008, vol. 51, # 20, p. 6571 - 6580.
[3] Patent: WO2012/116666, 2012, A1, .
[4] Medicinal Chemistry Research, 2014, vol. 23, # 10, p. 4482 - 4490.
[5] Medicinal Chemistry Research, 2014, vol. 23, # 10, p. 4482 - 4490.
  • 3
  • [ 55477-35-5 ]
  • [ 10025-87-3 ]
  • [ 7153-13-1 ]
References: [1] Chemische Berichte, 1905, vol. 38, p. 3397.
 

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Technical Information

Categories

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