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Chemical Structure| 56032-35-0

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Product Details of [ 56032-35-0 ]

CAS No. :56032-35-0
Formula : C6H6ClN3O3S
M.W : 235.65
SMILES Code : O=[N+](C1=C(OC)N=C(SC)N=C1Cl)[O-]
MDL No. :MFCD29922353
InChI Key :LHFPJGXWWXFDAC-UHFFFAOYSA-N
Pubchem ID :21517683

Safety of [ 56032-35-0 ]

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

Computational Chemistry of [ 56032-35-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 3
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 54.08
TPSA ?

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

106.13 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.53
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.

1.77
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.

0.74
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

0.02
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.24

Water Solubility

Log S (ESOL):?

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

-2.77
Solubility 0.402 mg/ml ; 0.0017 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.

-4.0
Solubility 0.0235 mg/ml ; 0.0000999 mol/l
Class?

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

Moderately 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

-2.28
Solubility 1.23 mg/ml ; 0.00522 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

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

Yes
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.

-6.22 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

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)

2.46

Application In Synthesis of [ 56032-35-0 ]

* 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 [ 56032-35-0 ]

[ 56032-35-0 ] Synthesis Path-Downstream   1~12

YieldReaction ConditionsOperation in experiment
a. 4-Chloro-6-methoxy-2-methylthio-5-nitro-pyrimidine, m.p. 77.5-79.5C (petroleum ether);
  • 2
  • [ 67-56-1 ]
  • [ 124-41-4 ]
  • [ 1979-96-0 ]
  • [ 56032-35-0 ]
YieldReaction ConditionsOperation in experiment
85% at 20℃; for 3.0h; Step 3: A mixture of 4,6-Dichloro-2-methylthio-5-nitropyrimidine (5.25 g, 21.88 mmol) in methanol (40 mL) was treated with sodium methoxide (1.3 g, 24.06 mmol). The mixture was stirred at room temperature for 3 h. At this point the reaction was poured onto ice to give a brown solid which was filtered and washed with water. The solid was dried under vacuo to give 4-Chloro-6-methoxy-2-methylthio-5-nitropyrimidine (4.40 g, 85%) as a brown solid. LRMS for C6H6Cl1N3O3S (M+H)+ at m/z=235. The NMR spectrum obtained on the sample is compatible with its structure.
  • 3
  • [ 1147550-11-5 ]
  • [ 56032-35-0 ]
  • [ 958000-43-6 ]
YieldReaction ConditionsOperation in experiment
46% With acetic acid; at 85℃; for 6.0h; Step 4: A mixture of 4-Chloro-6-methoxy-2-methylthio-5-nitropyrimidine (4.40 g, 18.68 mmol) in acetic acid (30 mL) was treated with ammonium thiocyanate (2.84 g, 37.37 mmol). The mixture was stirred at 85 C. for 6h. After partial evaporation the liquid was poured onto ice to give a brown solid which was filtered and washed with water. The solid was dried under vacuo to give 4-Methoxy-2-methylthio-5-nitro-6-thicyanato-pyrimidine (2.20 g, 46%) as a brown solid. LRMS for C7H6N4O3S2 (M+H)+ at m/z=258. The NMR spectrum obtained on the sample is compatible with its structure.
  • 4
  • [ 645-36-3 ]
  • [ 56032-35-0 ]
  • [ 1476056-64-0 ]
YieldReaction ConditionsOperation in experiment
69% With triethylamine; In isopropyl alcohol; at 20℃; for 0.75h; 2,2-Diethoxyethylamine (470 μL, 3.23 mmol) was added to a suspension of pyrimidine 9 (0.63 g, 2.67 mmol) in i-PrOH (30 mL), and the mixture was stirred at r.t. until the starting compound has dissolved. Et3N (560 μL, 4.0 mmol) was then added and the mixture was stirred for a further 45 min. H2O (50 mL) was added and the product was extracted with CH2Cl2 (2 × 50 mL). The organic layers were combined, washed with H2O (2 × 20 mL), dried (Na2SO4), and concentrated. The residue was purified by flash chromatography(silica gel, CH2Cl2; Rf = 0.42) to give a yellow solid; yield: 0.61 g(69%); mp 65.5-67.5 C.IR (KBr): 3380 (NH) cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.27 (t, J = 6.9 Hz, 6 H, 2 × CH3),2.55 (s, 3 H, SCH3), 3.60 (dq, 2J = 9.3 Hz, 3J = 6.9 Hz, 2 H,2 × CHAHBCH3), 3.72-3.83 (m, 4 H, NCH2 and 2 × CHAHBCH3),4.09 (s, 3 H, OCH3), 4.68 (t, J = 5.4 Hz, 1 H, OCH), 8.84 (br s, 1 H,NH).13C NMR (75 MHz, CDCl3): δ = 14.8, 15.6, 44.3, 55.7, 63.2, 100.5,113.5, 156.6, 163.8, 174.6.Anal. Calcd for C12H20N4O5S: C, 43.36; H, 6.07. Found: C, 43.68;H, 6.11.
  • 5
  • [ 67-56-1 ]
  • [ 1979-96-0 ]
  • [ 56032-35-0 ]
YieldReaction ConditionsOperation in experiment
64% With sodium carbonate; at 20℃; for 6.0h; Na2CO3 (0.49 g, 4.62 mmol) was added to a soln of pyrimidine 717(1.0 g, 4.16 mmol) in MeOH (30 mL), and the mixture was stirredat r.t. for 6 h. H2O (150 mL) was added and the resulting precipitate was collected by filtration, dried, and crystallized (hexane) to givea colorless solid; yield: 0.63 g (64%); mp 78-79 C (Lit.19 77.5-79.5 C).1H NMR (300 MHz, CDCl3): δ = 2.60 (s, 3 H, SCH3), 4.13 (s, 3 H,OCH3).13C NMR (75 MHz, CDCl3): δ = 14.8, 56.2, 128.8, 151.4, 160.9,173.8.Anal. Calcd for C6H6ClN3O3S: C, 30.58; H, 2.57. Found: C, 30.75;H, 2.54.
  • 6
  • [ 56032-35-0 ]
  • [ 1476056-69-5 ]
  • 7
  • [ 56032-35-0 ]
  • tert-butyl 4'-amino-5'-(2-aminobenzo[d]oxazol-5-yl)-2'-(methylthio)-6'-oxo-5',6'-dihydrospiro[azetidine-3,7'-pyrrolo[3,2-d]pyrimidine]-1-carboxylate [ No CAS ]
  • 8
  • [ 56032-35-0 ]
  • tert-butyl 4'-amino-5'-(2-aminobenzo[d]oxazol-5-yl)-2'-(methylthio)-5',6'-dihydrospiro[azetidine-3,7'-pyrrolo[3,2-d]pyrimidine]-1-carboxylate [ No CAS ]
  • 9
  • [ 56032-35-0 ]
  • 1-(tert-butyl) 3-methyl 3-(6-amino-2-(methylthio)-5-nitropyrimidin-4-yl)azetidine-1,3-dicarboxylate [ No CAS ]
  • 10
  • [ 56032-35-0 ]
  • tert-butyl 4'-amino-2'-(methylthio)-6'-oxo-5',6'-dihydrospiro[azetidine-3,7'-pyrrolo[3,2-d]pyrimidine]-1-carboxylate [ No CAS ]
  • 11
  • [ 610791-05-4 ]
  • [ 56032-35-0 ]
  • 1-(tert-butyl) 3-methyl 3-(6-methoxy-2-(methylthio)-5-nitropyrimidin-4-yl)azetidine-1,3-dicarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
4.73 g With lithium hexamethyldisilazane; In tetrahydrofuran; at -78 - 20℃; for 22.0h; c) 1-(tert-butyl) 3-methyl 3-(6-methoxy-2-(methylthio)-5-nitropyrimidin-4-yl)azetidine-1,3-dicarboxylate (10) To a solution of 4-chloro-6-methoxy-2-methylsulfanyl-5-nitropyrimidine (4.27 g, 17.2 mmol, 1.0 eq.) (9) in tetrahydrofuran (86 ml) is added 1-(tert-butyl) 3-methyl azetidine-1,3-dicarboxylate (3.56 ml, 18.08 mmol, 1.1 eq.). The resulting heterogeneous mixture was cooled to -78 C. and 1M LiHMDS in THF (18.07 ml, 18.08 mmol, 1.1 eq.) was then added dropwise and the reaction mixture was stirred at room temperature for 22 hours. The reaction mixture was poured slowly into water and ethyl acetate. The layers were separated and the aqueous layer was subjected to re-extraction with ethyl acetate. The combined organic layers were washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel using dichloromethane in heptane from 50% to 100% to give the desired compound (1-(tert-butyl) 3-methyl 3-(6-methoxy-2-(methylthio)-5-nitropyrimidin-4-yl)azetidine-1,3-dicarboxylate (10)) in the form of a yellow powder (4.73 g, 66% yield).
  • 12
  • [ 1979-96-0 ]
  • C7H9N3O4S [ No CAS ]
  • [ 56032-35-0 ]
YieldReaction ConditionsOperation in experiment
With sodium methylate; In methanol; b) 4-chloro-6-methoxy-2-methylsulfanyl-5-nitropyrimidine (9) 4,6-Dichloro-2-methylsulfanyl-5-nitropyrimidine (10.0 g, 41.6 mmol) in 102 ml of methanol are added slowly (9.49 ml, 41.6 mmol) of sodium methoxide at 30% by weight (a pale yellow precipitate forms). The reaction medium is cooled to 0 C. and the precipitate is filtered off and then rinsed twice with methanol and dried in a vacuum oven at 40 C. to give 4.62 g of a pale yellow powder. The filtrate is concentrated to dryness and then resuspended in water, filtered and dried in a vacuum oven at 40 C. to obtain a further 5.5 g of pale yellow powder. The two fractions obtained contain 70% of the expected product (4-chloro-6-methoxy-2-methylsulfanyl-5-nitropyrimidine-(9)) and 30% of the dimethoxy analog.
 

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Technical Information

Categories

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