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Chemical Structure| 4316-98-7 Chemical Structure| 4316-98-7

Structure of 4316-98-7

Chemical Structure| 4316-98-7

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Product Details of [ 4316-98-7 ]

CAS No. :4316-98-7
Formula : C4H5ClN4
M.W : 144.56
SMILES Code : C1=NC(=C(N)C(=N1)N)Cl
MDL No. :MFCD00023270
InChI Key :VNSFICAUILKARD-UHFFFAOYSA-N
Pubchem ID :78010

Safety of [ 4316-98-7 ]

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

Computational Chemistry of [ 4316-98-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 35.85
TPSA ?

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

77.82 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.96
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

0.14
Log Po/w (WLOGP)?

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

0.31
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.

-0.63
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

0.28
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.21

Water Solubility

Log S (ESOL):?

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

-1.32
Solubility 6.95 mg/ml ; 0.0481 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.

-1.33
Solubility 6.75 mg/ml ; 0.0467 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

-1.53
Solubility 4.3 mg/ml ; 0.0297 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.

-7.08 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

2.0
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)

1.78

Application In Synthesis of [ 4316-98-7 ]

* 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 [ 4316-98-7 ]

[ 4316-98-7 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 4316-98-7 ]
  • [ 13754-19-3 ]
  • 2
  • [ 4316-94-3 ]
  • [ 4316-98-7 ]
YieldReaction ConditionsOperation in experiment
With water; iron;hydrogenchloride; In ethanol; at 85℃;Industry scale; 6-ChJoropyrimidine-4,5-diamine[00162] Iron dust (1000 g, 17.9 mol) was added to a solution of the crude 6-chloro-5- nitropyrimidin-4-amine (500 g, 2.87 mol) in ethanol (5000 mL) and water (1000 mL). A catalytic amount of concentrated hydrochloric acid (10 mL) was slowly added to the reaction mixture over a period of 20 minutes. During the course of the addition the reaction temperature was observed to increase to 85 C without external heating and the reaction mixture's color changed from yellow-brown to dark red. After the reaction mixture had cooled down to a temperature of 50 C, the slurry was filtered through a Celite pad, which was then washed with ethanol (3 x 250 mL). The resulting filtrate was concentrated under reduced pressure to give a yellow solid. This solid was then washed with hexane and dried under reduced pressure to give the title compound as a brown solid. (253 g, overall yield over two steps: 37.1% yield). NMR (400 MHz, DMSO-d6): 6 7.61 (s, 1H), 6.71 (broad s, 2H), 4.94 (broad s, 2H). MS (EI) for C4H5C1N4: 145 (MU+).
  • 3
  • [ 4316-98-7 ]
  • [ 108-24-7 ]
  • [ 92001-52-0 ]
YieldReaction ConditionsOperation in experiment
52% at 120.0℃; Step 2: A solution of 6-chloropyrimidine-4,5 -diamine (432 mg, 3.0 mmol) in acetic anhydride (5 mL) was heated to 120 C for overnight. The reaction mixture was concentrated and water was added, and then extracted with EtOAc. The organic layer was separated and washed with water and brine, dried over Na2S04 and concentrated. The residue was suspended in POCI3 (10 mL) and heated to 120 C for overnight. The reaction was concentrated and diluted with EtOAc and sat. NaHC03 solution. The organic layer was separated and washed with water and brine, dried over Na2S04 and concentrated. Purified by a flash column chromatography (0-30% EtOAc in petroleum ether) to give the desired product 6-chloro-8-methyl-9H-purine (263 mg, 52% yield). LC-MS: m/z 169 (M+H)+.
  • 4
  • [ 40004-69-1 ]
  • [ 4316-98-7 ]
  • 5-(6-chloro-9H-purin-8-yl)-2-methylthiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With trichlorophosphate; at 160℃; for 0.5h;Microwave irradiation; 6-chloropyrimidine-4,5-diamine (200mgs, 1.3mmol) and <strong>[40004-69-1]2-methylthiazole-5-carboxylic acid</strong> (218 mgs, 1 .5 mmol) were dissolved in phosphoryl chloride (4 mL) in a 10 mL microwave vial. The reaction mixture was stirred at 160°C for 30 min in a microwave reactor. After cooling down to room temperature reaction mixture was diluted with diethyl-ether and solids filtered out. Solids were re-dissolved in dichloromethane and extracted with aqueous saturated solution of sodium bicarbonate. Organic layer was dried over Mg2SO4 and evaporated under reduced pressure. Solids were suspended in ACN and stirred over 1 hr. Solids were filtered out to yield 5-(6-chloro-9H-purin-8-yl)-2- methylthiazole.
  • 5
  • [ 1445-45-0 ]
  • [ 4316-98-7 ]
  • [ 92001-52-0 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In acetonitrile; at 120.0℃; General procedure: 6-Chloro-4,5-diaminopyrimidine (5 g, 35 mmol), ethyl orthopropionate49 mL and triethylamine 48 mL were dissolved in50 mL acetonitrile and stirred at 120 C overnight. The mixturewas concentrated in vacuum to yield the crude product 61 (5 g).
 

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Technical Information

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