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Chemical Structure| 4316-94-3 Chemical Structure| 4316-94-3

Structure of 4316-94-3

Chemical Structure| 4316-94-3

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Product Details of [ 4316-94-3 ]

CAS No. :4316-94-3
Formula : C4H3ClN4O2
M.W : 174.55
SMILES Code : C1=NC(=C([N+]([O-])=O)C(=N1)N)Cl
MDL No. :MFCD00127772
InChI Key :BWLOHIMQWHFSQF-UHFFFAOYSA-N
Pubchem ID :101229

Safety of [ 4316-94-3 ]

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

Computational Chemistry of [ 4316-94-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 40.27
TPSA ?

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

97.62 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.57
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

1.53
Log Po/w (WLOGP)?

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

0.63
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.

-1.08
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

-1.07
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.12

Water Solubility

Log S (ESOL):?

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

-2.22
Solubility 1.04 mg/ml ; 0.00597 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.

-3.19
Solubility 0.113 mg/ml ; 0.000647 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

-1.29
Solubility 9.01 mg/ml ; 0.0516 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.

-6.28 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

2.0 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)

2.02

Application In Synthesis of [ 4316-94-3 ]

* 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 [ 4316-94-3 ]

[ 4316-94-3 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 110-91-8 ]
  • [ 4316-94-3 ]
  • [ 24957-88-8 ]
YieldReaction ConditionsOperation in experiment
87.6% With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; In acetonitrile; at 25℃; for 3.5h;Inert atmosphere; General procedure: 6-Chloro-5-nitropyrimidine-4-amine (0.5mmol), amine (1.5mmol), Pd2(dba)3 (0.01mmol), R-BINAP (0.03mmol) and potassium carbonate (0.7mmol) were dissolved in acetonitrile (5mL). The solution was stirred at room temperature for 3.5h under an argon atmosphere. The resulting reaction mixture was treated with saturated brines (50mL) and extracted with acetonitrile (3×25mL), and dried with anhydrous Na2SO4. The anhydrous Na2SO4 was removed by filtration and the filtrate was concentrated. The residue was washed with ethyl acetate (3×2mL) and diethyl ether (3×2mL), filtered and dried under vacuum.
  • 3
  • [ 67-56-1 ]
  • [ 4316-94-3 ]
  • [ 124-41-4 ]
  • [ 73318-75-9 ]
  • 4
  • [ 4316-94-3 ]
  • [ 108-91-8 ]
  • [ 23120-19-6 ]
YieldReaction ConditionsOperation in experiment
92.2% With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; In acetonitrile; at 25℃; for 3.5h;Inert atmosphere; General procedure: 6-Chloro-5-nitropyrimidine-4-amine (0.5mmol), amine (1.5mmol), Pd2(dba)3 (0.01mmol), R-BINAP (0.03mmol) and potassium carbonate (0.7mmol) were dissolved in acetonitrile (5mL). The solution was stirred at room temperature for 3.5h under an argon atmosphere. The resulting reaction mixture was treated with saturated brines (50mL) and extracted with acetonitrile (3×25mL), and dried with anhydrous Na2SO4. The anhydrous Na2SO4 was removed by filtration and the filtrate was concentrated. The residue was washed with ethyl acetate (3×2mL) and diethyl ether (3×2mL), filtered and dried under vacuum.
  • 5
  • [ 4316-94-3 ]
  • [ 124-40-3 ]
  • [ 6311-26-8 ]
  • 6
  • [ 4316-94-3 ]
  • [ 109-89-7 ]
  • <i>N</i>4,<i>N</i>4-diethyl-5-nitro-pyrimidine-4,6-diyldiamine [ No CAS ]
  • 7
  • [ 4316-94-3 ]
  • [ 109-55-7 ]
  • [ 102540-82-9 ]
  • 8
  • [ 4316-94-3 ]
  • [ 62-53-3 ]
  • [ 40816-36-2 ]
YieldReaction ConditionsOperation in experiment
91.2% With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; In acetonitrile; at 25℃; for 3.5h;Inert atmosphere; General procedure: 6-Chloro-5-nitropyrimidine-4-amine (0.5mmol), amine (1.5mmol), Pd2(dba)3 (0.01mmol), R-BINAP (0.03mmol) and potassium carbonate (0.7mmol) were dissolved in acetonitrile (5mL). The solution was stirred at room temperature for 3.5h under an argon atmosphere. The resulting reaction mixture was treated with saturated brines (50mL) and extracted with acetonitrile (3×25mL), and dried with anhydrous Na2SO4. The anhydrous Na2SO4 was removed by filtration and the filtrate was concentrated. The residue was washed with ethyl acetate (3×2mL) and diethyl ether (3×2mL), filtered and dried under vacuum.
  • 9
  • [ 4316-94-3 ]
  • [ 74-89-5 ]
  • [ 4094-00-2 ]
YieldReaction ConditionsOperation in experiment
98.9% With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; In acetonitrile; at 25℃; for 3.5h;Inert atmosphere; General procedure: 6-Chloro-5-nitropyrimidine-4-amine (0.5mmol), amine (1.5mmol), Pd2(dba)3 (0.01mmol), R-BINAP (0.03mmol) and potassium carbonate (0.7mmol) were dissolved in acetonitrile (5mL). The solution was stirred at room temperature for 3.5h under an argon atmosphere. The resulting reaction mixture was treated with saturated brines (50mL) and extracted with acetonitrile (3×25mL), and dried with anhydrous Na2SO4. The anhydrous Na2SO4 was removed by filtration and the filtrate was concentrated. The residue was washed with ethyl acetate (3×2mL) and diethyl ether (3×2mL), filtered and dried under vacuum.
  • 10
  • [ 4316-94-3 ]
  • [ 459-73-4 ]
  • [ 22386-74-9 ]
  • 11
  • [ 4316-94-3 ]
  • [ 2846-89-1 ]
  • 12
  • [ 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+).
  • 13
  • [ 4316-93-2 ]
  • [ 4316-94-3 ]
YieldReaction ConditionsOperation in experiment
93% With ammonium hydroxide; sodium hydrogencarbonate; In tetrahydrofuran; at 55℃; To a solution of the compound 4,6-dichloro-5-nitropyrimidine (9.7 g, 50 mmol) in tetrahydrofuran (100 mL) was added aqueous ammonia (100 mL) and sodium bicarbonate (4.6 g, 55 mmol), heated to 55 C and stirred overnight. The reaction was cooled to room temperature and the organic solvent was removed under reduced pressure. The residue was filtered and separated by flash column chromatography (dichloromethane: methanol = 100: 1) to give the title compound A: 6-chloro-5-nitropyrimidine- 4-amine (8.1 g, yield 93%).
With ammonium hydroxide; In methanol; diethyl ether; water; for 2.0h;Industry scale; 6-Chloro-5-nitropyrimidin-4-amine[00161] A solution of 28% aqueous ammonium hydroxide (670 mL, 5.35 mol, 1.04 equiv) was added in a drop-wise fashion to a rapidly stirred solution of the 4,6-dichloro-5- nitropyrimidine solid (1000 g, 5.16 mol, 1.00 equiv) in diethyl ether (4000 mL) and methanol (670 mL). The addition was carried out over a period of 2 hours. Upon completion of addition, the resulting yellow solid was filtered off, washed with water and hexane, and dried under reduced pressure to give the title compound as a yellow solid (yield: 675 g). This crude solid was used in the next step without any further purification. NMR (400 MHz, DMSO- d6): delta 8.97 (s, 1H), 7.91 (broad s, 2H). MS (EI) for C4H3CIN4O2: 175 (MH+).
  • 14
  • [ 110-87-2 ]
  • [ 4316-94-3 ]
  • [ 56270-92-9 ]
  • [ 64183-18-2 ]
  • 15
  • [ 5446-92-4 ]
  • [ 4316-94-3 ]
  • [ 63931-14-6 ]
  • 16
  • [ 4316-94-3 ]
  • [ 27467-92-1 ]
  • [ 63931-16-8 ]
  • 17
  • [ 4316-94-3 ]
  • [ 33761-31-8 ]
  • [ 55740-63-1 ]
  • 18
  • [ 4316-94-3 ]
  • [ 56270-92-9 ]
  • [ 56153-73-2 ]
  • 19
  • [ 4316-94-3 ]
  • [ 56270-92-9 ]
  • [ 56153-72-1 ]
  • 20
  • [ 4316-94-3 ]
  • [ 56270-92-9 ]
  • [ 56153-74-3 ]
  • 22
  • [ 4316-94-3 ]
  • [ 16206-18-1 ]
  • 23
  • [ 4316-94-3 ]
  • [ 616-30-8 ]
  • [ 85446-45-3 ]
  • 24
  • [ 4316-94-3 ]
  • [ 6066-83-7 ]
  • [ 127820-32-0 ]
  • 25
  • [ 4316-94-3 ]
  • [ 134-32-7 ]
  • [ 127820-28-4 ]
  • 26
  • [ 4316-94-3 ]
  • [ 78-96-6 ]
  • [ 85446-52-2 ]
  • 27
  • [ 4316-94-3 ]
  • [ 446-24-2 ]
  • [ 159976-36-0 ]
  • 28
  • [ 4316-94-3 ]
  • [ 51172-55-5 ]
  • [ 116384-41-9 ]
  • [ 116384-42-0 ]
  • 29
  • [ 4316-94-3 ]
  • [ 613-94-5 ]
  • [ 159976-35-9 ]
  • 30
  • [ 4316-94-3 ]
  • [ 100-51-6 ]
  • 4-amino-6-(benzyloxy)-5-nitropyrimidine [ No CAS ]
  • 31
  • [ 4316-94-3 ]
  • [ 112698-38-1 ]
  • 4-amino-6-<(4-methoxybenzyl)(2-oxo-2-phenylethyl)amino>-5-nitropyrimidine [ No CAS ]
  • 32
  • [ 67-56-1 ]
  • [ 4316-94-3 ]
  • [ 73318-75-9 ]
  • [ 163769-98-0 ]
  • 33
  • [ 4316-94-3 ]
  • [ 169769-56-6 ]
  • [2-(6-Amino-5-nitro-pyrimidin-4-ylamino)-ethoxymethyl]-phosphonic acid diisopropyl ester [ No CAS ]
  • 34
  • [ 4316-94-3 ]
  • [ 169769-57-7 ]
  • [(R)-2-(6-Amino-5-nitro-pyrimidin-4-ylamino)-1-methyl-ethoxymethyl]-phosphonic acid diisopropyl ester [ No CAS ]
 

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