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Chemical Structure| 934524-10-4 Chemical Structure| 934524-10-4

Structure of 934524-10-4

Chemical Structure| 934524-10-4

2,4-Dichloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine

CAS No.: 934524-10-4

4.5 *For Research Use Only !

Cat. No.: A114934 Purity: 97%

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Product Details of [ 934524-10-4 ]

CAS No. :934524-10-4
Formula : C13H9Cl2N3O2S
M.W : 342.20
SMILES Code : O=S(N1C=CC2=C(Cl)N=C(Cl)N=C21)(C3=CC=C(C)C=C3)=O
MDL No. :MFCD13193624
InChI Key :DTDGVNQSPAWHTH-UHFFFAOYSA-N
Pubchem ID :53486828

Safety of [ 934524-10-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 934524-10-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 21
Num. arom. heavy atoms 15
Fraction Csp3 0.08
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 81.58
TPSA ?

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

73.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.71
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

4.13
Log Po/w (WLOGP)?

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

4.36
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.

3.05
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

2.5
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.35

Water Solubility

Log S (ESOL):?

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

-4.96
Solubility 0.00375 mg/ml ; 0.000011 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-5.37
Solubility 0.00144 mg/ml ; 0.00000422 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

-5.74
Solubility 0.000621 mg/ml ; 0.00000182 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

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

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

Yes
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.

-5.46 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)

2.69

Application In Synthesis of [ 934524-10-4 ]

* 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 [ 934524-10-4 ]

[ 934524-10-4 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 1123-93-9 ]
  • [ 934524-10-4 ]
  • [ 1122710-25-1 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 90℃; for 3h; Example 19 N4-(benzo[D]thiazol-5-yl)-N2-(1H-indazol-6-yl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine To a solution of 2,4-dichloro-7-tosyl-pyrrolo[2,3-d]pyrimidine (0.1 g, 0.28 mmol) in n-butyl alcohol (0.8 mL) was added <strong>[1123-93-9]5-aminobenzothiazole</strong> (0.046 g, 0.31 mmol) and DIPEA (0.1 mL, 0.56 mmol) at room temperature. After heating at 90° C. for 3 h, the mixture was diluted with H2O, and the precipitates were collected by filtration to give N-(2-chloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzolthiazol-5-amine (0.19 g).
  • 2
  • [ 4138-26-5 ]
  • [ 934524-10-4 ]
  • [ 1192711-39-9 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In 1,4-dioxane; at 70℃; for 20h; A solution of 2,4-dichloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine (200 mg, 0.584 mmol), <strong>[4138-26-5]nipecotamide</strong> (75 mg, 0.586 mmol) and triethylamine (0.130 mL, 0.934 mmol) in dioxane (5 mL) was stirred at 70 0C for 20 h. Water and EtOAc were added. The organic phase was separated, dried over Na2SO4, concentrated in vacuo to give l-(2-chloro-7-tosyl- 7H-pyrrolo[2,3-d]pyrimidin-4-yl)<strong>[4138-26-5]piperidine-3-carboxamide</strong> (250 mg).
  • 3
  • [ 934524-10-4 ]
  • [ 1197953-47-1 ]
  • (2-((2-chloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide [ No CAS ]
YieldReaction ConditionsOperation in experiment
63.2% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 110℃;Inert atmosphere; Add compound 35 (3.4 g, 10 mmol) to a 100 mL single-mouth bottle with magnetic stirringAnd DMF (20 mL), stirred and dissolved, and added compound 36 (1.7 g, 10 mmol)And N,N-diisopropylethylamine (DIPEA, 1.3 g, 10 mmol),The temperature was raised to 110 C under a nitrogen atmosphere and the reaction was stirred overnight. Cool to room temperature,Add water (60 mL), extract with ethyl acetate (50 mL×3),Washed (100 mL×2), dried over anhydrous sodium sulfate, filtered and concentrated.The residue was passed through a silica gel column to give a white solid3.0g,The yield was 63.2%.
63.2% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 110℃;Inert atmosphere; Compound 10a (3.4 g, 10 mmol) was added to a 100 mL single-mouth bottle with magnetic stirring.And DMF (20 mL), stirred and dissolved, and added compound 11a (1.7 g, 10 mmol)And DIPEA (1.3g, 10mmol),The temperature was raised to 110 C under a nitrogen atmosphere and stirred to react overnight. Cool to room temperature,Add water (60 mL), extract with ethyl acetate (50 mL×3),Washed (100 mL×2), dried over anhydrous sodium sulfate, filtered and concentrated.The residue was passed through a silica gel column to give a white solid3.0 g, the yield was 63.2%.
With N-ethyl-N,N-diisopropylamine; at 100℃; for 5.0h; General procedure: To a solution of 8 (1 equiv) in n-BuOH (20mL), corresponding amines (1.1 equiv) and N-ethyl-N-isopropylpropan-2-amine (1.2 equiv) were added. The mixture was stirred at 100C for 5h. The mixture was diluted with EtOAc and washed successively with water and brine. The organic layer was dried over Na2SO4, filtered, and evaporated. The resulting intermediate was purified by chromatography.
  • 4
  • [ 934524-10-4 ]
  • [ 1211443-58-1 ]
 

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