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Chemical Structure| 15598-33-1 Chemical Structure| 15598-33-1

Structure of 15598-33-1

Chemical Structure| 15598-33-1

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Product Details of [ 15598-33-1 ]

CAS No. :15598-33-1
Formula : C4H2Cl2FN3
M.W : 181.98
SMILES Code : NC1=NC(Cl)=C(F)C(Cl)=N1
MDL No. :MFCD11870221
InChI Key :PSEWFMLZDMIBMC-UHFFFAOYSA-N
Pubchem ID :15221577

Safety of [ 15598-33-1 ]

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

Computational Chemistry of [ 15598-33-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 36.41
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.

1.42
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

1.88
Log Po/w (WLOGP)?

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

1.93
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.

1.05
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

2.09
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.67

Water Solubility

Log S (ESOL):?

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

-2.6
Solubility 0.461 mg/ml ; 0.00253 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.

-2.59
Solubility 0.468 mg/ml ; 0.00257 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

-2.8
Solubility 0.286 mg/ml ; 0.00157 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.

-6.08 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)

1.77

Application In Synthesis of [ 15598-33-1 ]

* 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 [ 15598-33-1 ]

[ 15598-33-1 ] Synthesis Path-Downstream   1~4

  • 2
  • [ 109-06-8 ]
  • [ 669-96-5 ]
  • [ 15598-33-1 ]
YieldReaction ConditionsOperation in experiment
47% With trichlorophosphate; B. Preparation of 5-fluoro-4,6-dichloro-2-pyrimidineamine (4) 5-Fluoro-4,6-dihydroxy-2-pyrimidineamine (3) (450 mg, 3 mmol), phosphorous oxychloride (972 mg, 6 mmol) and 2-picoline (633 mg, 7 mmol) were charged to a 15 ml round bottom flask and heated at 110 C. for 3.5 hours. The reaction mixture was then poured onto ice. The ice solution was neutralized to pH 5.5 and refluxed under argon for 1 hour. The solution was cooled on ice and the precipitate was collected, yielding (4) as a brown solid (268 mg, 47%): MS (70 eV, EI) m/z (relative intensity) 101 (M+, 181) 183 (66), 146 (56), 85 (34), 154 (28). Exact Mass Calcd for C4 H2 N3 Cl2 F: 180.9610. Found: 180.9607.
  • 3
  • [ 15598-33-1 ]
  • 5-Fluoro-6-chloro-2,4-pyrimidinediamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With ammonium hydroxide; In ethanol; C. Preparation of 5-Fluoro-6-chloro-2,4-pyrimidinediamine (5) 5-Fluoro-4,6-dichloro-2-pyrimidineamine (4) (204 mg, 1 mmol) and ammonium hydroxide (15 ml) were charged to a sealed tube and ethanol (1.5 ml) added. The tube was heated at 100 C. for 24 hours. The solution was concentrated. The residue was absorbed on silica gel and chromatographed (elution with ethyl acetate), yielding (5) as a white powder (118 mg, 65%): MS (70 eV, EI) m/z (relative intensity) 162 (M+, 100), 43 (92), 164 (33), 127 (29), 135 (16). Exact Mass Calcd for C4 H4 N4 ClF: 162.0108. Found: 162.0100.
  • 4
  • C7H7Cl2FN4 [ No CAS ]
  • [ 15598-33-1 ]
YieldReaction ConditionsOperation in experiment
90% With water; at 50 - 70℃; Cool the system to 50 ~ 60 C,The syrupy reaction droplets were added to 350 g of cold water for quenching reaction.The reaction solution gradually dissolves under stirring.Control the temperature inside the kettle to not exceed 50 C,After the addition,The reaction solution is directly heated to an internal temperature of 60 to 70 C.Re-reaction for 3 to 4 hours,The system gradually precipitates the target product.Cool to an internal temperature of 5 to 10 C,The reaction solution is centrifuged.Get the filter cake,Then the filter cake is rinsed with 100 ml of 5% ammonia water.Check the pH value of the lotion 8~9,The filter cake is a white solid product. Solid product is infrared dried,Obtained 32.8 g of solid product,The product has been confirmed by nuclear magnetics, and the product structure is correct.The liquid phase content of the product is 98.2%, the water content is 0.24%, and the yield is 90%.
 

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Technical Information

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