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Chemical Structure| 1398507-08-8

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Product Details of [ 1398507-08-8 ]

CAS No. :1398507-08-8
Formula : C11H8ClN5
M.W : 245.67
SMILES Code : N#CC1=CC=C(NC2=NC(Cl)=CC(N)=N2)C=C1
MDL No. :MFCD24682776
InChI Key :WIFUACDBVMFQGM-UHFFFAOYSA-N
Pubchem ID :71465001

Safety of [ 1398507-08-8 ]

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

Computational Chemistry of [ 1398507-08-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 65.71
TPSA ?

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

87.62 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.96
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

2.41
Log Po/w (WLOGP)?

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

2.34
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.

1.14
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

1.53
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.87

Water Solubility

Log S (ESOL):?

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

-3.27
Solubility 0.131 mg/ml ; 0.000535 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.

-3.89
Solubility 0.0315 mg/ml ; 0.000128 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

-4.57
Solubility 0.0066 mg/ml ; 0.0000269 mol/l
Class?

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

Moderately 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

Yes
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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.09 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)

2.25

Application In Synthesis of [ 1398507-08-8 ]

* 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 [ 1398507-08-8 ]

[ 1398507-08-8 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 1398507-08-8 ]
  • [ 98-88-4 ]
  • [ 1404118-66-6 ]
YieldReaction ConditionsOperation in experiment
Example 4: Preparation of N-[6-Chloro-2-(4-cyanophenylamino)pyrimidin-4- yl]benzamide (IV)1400 ml of N-methyl pyrrolidine and 140 g of 4-(4-Amino-6-chloropyrimidin-2- ylamino)benzonitrile was charged into a reaction vessel. To this was added 85.49 g of dimethylamino pyridine and 87.2 lg of diazabicyclo undecene and stirred for 30 mins. To the reaction mixture was added 27.36 g of benzoyl chloride and stirred at RT for 30mins and heated to 80- 85 C and maintained the same for 4 hrs. After completion of the reaction, the reaction mass was cooled to RT and was added 1400 ml of water followed by 1400 ml of 50% carbonate solution. Reaction mass was extracted with 1400 ml of dichloromethane and the dichloromethane layer was washed with 700 ml of water. The organic layers were separated and dried over of anhydrous sodium sulfate and filtered; distilled off dichloromethane and the solid was isolated.
175 g With dmap; In acetonitrile; at 27 - 78℃; for 7h; Example 5 Preparation of N-[6-chloro-2-(4-cyanophenylamino)pyrimidin-4-yl]benzamide (IV) 3000 ml of acetonitrile; 150 g of <strong>[1398507-08-8]4-(4-amino-6-chloropyrimidin-2-ylamino)benzonitrile</strong> and 187 g of dimethylaminopyridine were added into a reaction vessel at 27+-3 C. and heated to 63+-2 C. under stirring. To the reaction mixture was added 425 ml of benzoyl chloride and heated to 78+-3 C. and maintained the same for 7 hrs. 50% of acetonitrile was distilled off from the reaction mixture and the reaction mixture cooled to 63+-2 C. To the reaction mixture was added 1500 ml of water, stirred for 15 mins at the same temperature and filtered. The obtained product solid was washed with water and suck dried. The wet cake was taken into an RB flask and 1500 ml of methanol was added, stirred and filtered. The obtained solid was washed with 150 ml of methanol and dried under vacuum. Dry weight: 165-175 gm.
  • 2
  • [ 5637-42-3 ]
  • [ 1398507-08-8 ]
  • 4
  • [ 1398507-08-8 ]
  • [ 1404118-67-7 ]
  • 5
  • [ 1398507-08-8 ]
  • [ 1404118-68-8 ]
  • 6
  • [ 1398507-07-7 ]
  • [ 1398507-08-8 ]
YieldReaction ConditionsOperation in experiment
Example 2:Preparation of 4-(4-Amino-6-chloropyrimidin-2-ylamino)benzonitriIe (III):1900 ml of phosphorus oxychloride was added to a reaction vessel, to this was added 190 g of 4-(4-Amino-6-hydroxypyrimidin-2-ylamino)benzonitrile under stirring at RT. The reaction mass was slowly heated to 80- 85 C and maintained at same temperature for 16- 18 hr. After completion of the reaction, phosphorous oxychloride was distilled off and stripped with 950 ml of ethyl acetate and slowly added 1900 ml of chilled water and adjusted pH of the reaction mass to 9- 10 with 950 ml of 50% aqueous potassium carbonate. The solid was filtered and dried under vacuum at 55- 60 C overnight.
180 g With trichlorophosphate; at 27 - 97℃; for 7h; Example 3 Preparation of 4-(4-amino-6-chloropyrimidin-2-ylamino)benzonitrile (III) 1500 ml of phosphorus oxychloride and 300 g of 4-(4-Amino-6-hydroxypyrimidin-2-ylamino)benzonitrile at 27+-3 C. were added to the reaction vessel and heated to 97+-3 C.; and maintained at same temperature for 7 hrs. After completion of the reaction, ?50% of phosphorous oxychloride was distilled off under vacuum at 83+-2 C. and the reaction mixture was cooled to 30+-5 C. In a clean RB flask were added 1000 g of ice and 1000 mL of water and such was slowly added the above obtained reaction mass. The pH of the reaction mass was adjusted to 9.0+-0.5 with 50% potassium carbonate solution in water at 5+-5 C. The reaction mixture was stirred, filtered and the obtained solid was washed with 600 ml of water and suck dried. The wet solid was charged into a RB flask at 27+-3 C. to which was added 600 ml of water. The resulting wet solid was taken into a RB flask and 600 ml of water was added, stirred, and filtered. The obtained solid was washed with water and suck dried. 3000 ml of ethyl acetate was charged into a RB flask and to this was added the obtained solid and heated to 43+-3 C. The reaction mass was stirred for 20 mins and filtered hot. The residue was washed with ethyl acetate and filtrate (1) collected at 27+-3 C. The obtained solid was again taken in RB flask to which was added 1500 ml of ethyl acetate and heated to 43+-3 C., stirred and the hot reaction mass filtered and the filtrate (2) collected. Both filtrates (1) and (2) were taken and distilled off solvent at 47+-3 C. To the residue was added 900 ml of heptane and cooled to 27+-3 C. and was again added 1100 ml of heptane, stirred, the solid filtered and suck dried, and the solid was washed with heptane. The obtained solid was dried under vacuum. To the obtained 190 g of crude was added 380 ml of dimethyl formamide and 20.4 ml of 1,8-diazabicycloundec-7-ene under stirring at 27+-3 C. and the reaction mass heated to 47+-3 C. To the obtained clear solution was added 760 ml of water and stirred for 1 hr. The reaction mass was cooled and filtered. The solid was washed with 760 mL of water twice and suck dried. The solid was washed with 48 ml of chilled methanol and the solid suck dried. The obtained solid was further dried under vacuum to yield the title compound. Dry weight: 150-180 gm.
  • 7
  • [ 873-74-5 ]
  • [ 1398507-08-8 ]
  • 8
  • [ 10132-07-7 ]
  • [ 873-74-5 ]
  • [ 1398507-08-8 ]
YieldReaction ConditionsOperation in experiment
73% In iso-butanol; at 20 - 102℃; for 21h; Example 7: Preparation of 4-(4-amino-6-chloropyrimidin-2-ylamino)benzonitrile ("Compound la")To a solution of 4-aminobenzonitrile (ABN; 7 g; 59.3 mmol) in 2-butanol (190 ml), 2,6- dichloropyrimidin-4-amine ("DCAP"; 10.2 g; 62.2 mmol) was added at room temperature. The resulting suspension was heated to reflux (102 C) and stirred for 20 hours. The suspension was then cooled to 20-25 C and stirred for lhour at 20-25 C. A solid was separated from the suspension by filtration and washed with 2-butanol (20 ml) and dried (2h/ 50 C/ 10 mbar). Yield: 12.20 g (73.0 %) of 4-(4-amino-6-chloropyrimidin-2-ylamino)benzonitrile hydrochloride.Purity (HPLC/ MS): 99.0 Area %
  • 9
  • [ 1398507-08-8 ]
  • [ 1398507-09-9 ]
YieldReaction ConditionsOperation in experiment
423 mg With bromine; In methanol; at 0 - 5℃; for 2.16667h; Example 2a: Preparation of 4-(4-amino-5-bromo-6-chloropyrimidin-2-ylamino) benzonitrile ("Compound 3a")A suspension of <strong>[1398507-08-8]4-(4-amino-6-chloropyrimidin-2-ylamino)benzonitrile</strong> ("<strong>[1398507-08-8]CAPBN</strong>", compound la; 0.4 g; 1.628 mmol) in methanol (5 ml) was cooled to 0-5 C. Bromine (167.2 mu?; 3.26 mmol; 2 eq) was added dropwise to the suspension over 10 minutes. The resulting reaction mixture was stirred at 0-5 C for 2 hours, and then water (0.83 ml) and 10 % aqueous NaOH (1.95 ml; 4.88 mmol; 3 eq) was added dropwise. The resulting suspension was stirred lhour at 0- 5 C. A solid was separated from the suspension by filtration and washed with a MeOH / water mixture (1 : 1 ; 3 ml), and dried (4h/ 40 CI 10 mbar).Yield: 423 mg (80.1 %) of 4-(4-amino-5-bromo-6-chloropyrimidin-2-ylamino)benzonitrile. Purity (HPLC/ MS): 95.71 Area %M+ 326.4 (± 2)1H NMR (DMSO-de, delta): 10.06 (s, 1H, NH), 7.96 (d, 2H, Ph-b, Ji=8.8 Hz), 7.70 (d, 2H, Ph-c, Ji=8.8 Hz), 7.50-6.50 (br, 2H, NH2)13C NMR (DMSO-^6, delta): 161.9 (s, C2), 157.0 (s, C6), 156.7 (s, C4), 144.7 (s, Ph-a), 132.9 (d, Ph-c), 1 19.6 (s, CN), 1 18.5 (d, Ph-b), 102.6 (s, Ph-d), 89.8 (s, C5)1H NMR and 13C NMR spectra for this product are shown in figures 1-2 and 3-4, respectively.
  • 10
  • 4-(4-amino-6-chloropyrimidin-2-ylamino)benzonitrile hydrochloride [ No CAS ]
  • [ 1398507-08-8 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In water; acetone; at 0 - 40℃; for 3.08333h; Example lb: Preparation of 4-(4-amino-6-chloropyrimidin-2-ylamino)benzonitrile ("Compound la")To the suspension of 2,6-dichloropyrimidin-4-amine (DCAP, 16.7 g, 101.8 mmol) and 4- aminobenzonitrile (ABN, lOg, 84.7 mmol) in water (420 ml), concentrated hydrochloric acid (25.8 ml, 304.3 mmol) was added. The reaction mixture was heated to 100 C and stirred for 2h. Additional hydrochloric acid (25.8 ml, 304.3 mmol) was added, and the reaction mixture was stirred for another 2h. A second portion of DCAP (5.57 g, 33.9 mmol) was added, and the stirring was continued for an additional hour. The reaction mixture was then cooled to 0-5 C, and left stirring over lh. The obtained suspension was filtered and the collected solid crude product was washed with water (200 ml) and dried (15h / 65 C/10 mbar).Yield: 20.2 g (85%) of 4-(4-amino-6-chloropyrimidin-2-ylamino)benzonitrile, hydrochloride saltPurity (HPLC/ MS): 74 Area %.M+ - HC1 = 246The 4-(4-amino-6-chloropyrimidin-2-ylamino)benzonitrile, hydrochloride salt (20.2 g, 71.6 mmol) was ground using mortar and pestle and suspended in acetone (50 ml). Aqueous sodium hydroxide (10%, 36.7g, 91.9 mmol) was added dropwise over 5 min. The resulting suspension was heated at 40 C for 40 min. Water (100 ml) was added dropwise over 25 min, and the reaction mixture was stirred for an additional 15 min at 40 C. The obtained suspension was cooled to room temperature over 40 min and then stirred at 0-5 C for lh. The crude product was filtered off and washed with water (50 ml) and dried (15h / 65 C/10 mbar).Yield: 15.8 g (90%) of 4-(4-amino-6-chloropyrimidin-2-ylamino)benzonitrilePurity (HPLC/ MS): 78 Area %.M+ 246Total yield: 76.5%
  • 11
  • [ 23585-49-1 ]
  • [ 1398507-08-8 ]
  • 4-((4-amino-6-(3-(hydroxymethyl)-1H-pyrazol-1-yl)pyrimidin-2-yl)amino)benzonitrile [ No CAS ]
  • 12
  • [ 1398507-08-8 ]
  • 3-(methylsulfonamido)phenylboronic acid [ No CAS ]
  • N-(3-(6-amino-2-((4-cyanophenyl)amino)pyrimidin-4-yl)phenyl)methanesulfonamide [ No CAS ]
  • 13
  • [ 10132-07-7 ]
  • [ 104-15-4 ]
  • [ 873-74-5 ]
  • [ 1398507-08-8 ]
 

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