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Chemical Structure| 1186647-69-7 Chemical Structure| 1186647-69-7

Structure of 1186647-69-7

Chemical Structure| 1186647-69-7

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Product Details of [ 1186647-69-7 ]

CAS No. :1186647-69-7
Formula : C6H3ClIN3
M.W : 279.47
SMILES Code : ClC1=NC=CC2=C1C(=N[NH]2)I
MDL No. :MFCD16877655
InChI Key :PBVPGWHQJRFJQU-UHFFFAOYSA-N
Pubchem ID :53249936

Safety of [ 1186647-69-7 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H319
Precautionary Statements:P301+P310-P305+P351+P338
Class:6.1
UN#:2811
Packing Group:

Computational Chemistry of [ 1186647-69-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 9
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 51.62
TPSA ?

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

41.57 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.11
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

2.13
Log Po/w (WLOGP)?

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

2.22
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.

1.7
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

3.18
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.07

Water Solubility

Log S (ESOL):?

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

-3.52
Solubility 0.0844 mg/ml ; 0.000302 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.

-2.63
Solubility 0.648 mg/ml ; 0.00232 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

-4.1
Solubility 0.0221 mg/ml ; 0.0000791 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

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.

-6.49 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<0.0
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)

2.09

Application In Synthesis of [ 1186647-69-7 ]

* 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 [ 1186647-69-7 ]

[ 1186647-69-7 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 871836-51-0 ]
  • [ 1186647-69-7 ]
YieldReaction ConditionsOperation in experiment
92% With iodine; potassium hydroxide; In 1,4-dioxane; at 75℃; for 4h; A solution of <strong>[871836-51-0]4-chloro-1H-pyrazolo[4,3-c]pyridine</strong> (1.5 g, 9.77 mmol, 1.00 equiv), 1,4-dioxane(25 mL), potassium hydroxide (2.0 g, 35.65 mmol, 3.60 equiv), and iodine (4.95 g, 19.50 mmol,2.00 equiv) was stuffed for 4 h at 75 °C. The reaction was quenched by saturated aqueous sodium thiosulfate pentahydrate and the solids were collected by filtration. This resulted in 2.5 g (92percent) of the title compound as a light yellow solid. LC-MS (ES, mlz): 280 [M+H].
85% With N-iodo-succinimide; In N,N-dimethyl-formamide; at 100℃; To a solution of 4-chloro-lH-pyrazolo[4,3-c]pyridine (5.5 g, 36 mmol) in DMF (50 mL) was added NIS (6.9 g, 69 mmol). The resulted mixture was stirred at 100 °C overnight. Then the mixture was cooled and diluted with water, the precipitate was collected by filtration and dried to to give 4-chloro-3-iodo-lH-pyrazolo[4,3-c]pyridine (8.5 g, 85percent) as a light yellow solid.
72% With iodine; potassium hydroxide; In 1,4-dioxane; at 75℃; for 4h; To a mixture of 4-chloro-1H-pyrazolo [4, 3-c] pyridine (5.8 g, 38 mmol, synthesized according to WO 2010106333A1 and WO 2012038743A1) and KOH (8 g, 142 mmol) in dioxane (100 mL) at room temperature was added iodine (19 g, 76 mmol) . The reaction mixture was stirred at 75 for 4 h and then allowed to cool to room temperature. The solution was diluted with saturated Na2S2O3(aq) and the resulting precipitate was filtered and dried to give a yellow solid (4.1 g) . The filtrate was left standing for 3 days and filtration of the resulting precipitate yielded a further 3.55 g of the product. Combined yield (7.65 g, 72) .1H NMR (400 MHz, CDCl3) delta ppm 7.65 (d, J 6.0 Hz, 1H) , 8.13 (d, J 6.0 Hz, 1H) , 14.22 (s, 1H) . m/z (ESI)+: 280 [M+H]+
62% With N-iodo-succinimide; In N,N-dimethyl-formamide; at 80℃; for 3h; A solution of <strong>[871836-51-0]4-chloro-1H-pyrazolo[4,3-c]pyridine</strong> (102) (30 mg, 0.196 mmol) and NIS (66 mg 1.5 eq, 0.249mmol) in DMF (1 mL) was heated to 80 °C for 3 h. The mixture was concentrated in vacuo, brine (10 mL) was addedand then extracted with ethyl acetate (3 3 30 mL). The combined organic layer was washed with brine (10 mL), driedover MgSO4 and filtered. The filtrate was concentrated in vacuo to afford the desired product, 4-chloro-3-iodo-1Hpyrazolo[4,3-c]pyridine (103) (34 mg, 62percent yield) as a white solid. ESI-MS m/z : 277.85 [M - H]- .The product obtainedwas used directly in the next step without purification.
61% With iodine; potassium hydroxide; In 1,4-dioxane; at 75℃; for 4h; Intermediate 34-Chloro-3-iodo-1 H-pyrazolo[4, 3-c]pyridiTo a mixture of Intermediate 2 (5.8 g, 38 mmol) and KOH (8 g, 142 mmol) in dioxane (100 ml) at room temperature was added iodine (19 g, 76 mmol). The reaction mixture was stirred at 75 °C for 4 h, and then allowed to cool to room temperature. The solution was diluted with saturated Na2S203 (aq), and the resulting precipitate was filtered and dried to give a yellow solid (4.1 g). The filtrate was left standing for 3 days and filtration of the resulting precipitate yielded a further 2.35 g of the product. Combined yield (6.45 g, 61percent). 1 H NMR (400 MHz, DMSO-d6) delta ppm 7.64 (d, J=6.0 Hz, 1 H), 8.11 (d, J=6.0 Hz, 1 H); m/z (ES+APCI)+: 280 [M + H]+.
61% With iodine; potassium hydroxide; In 1,4-dioxane; at 75℃; for 4h; Intermediate 124-Chloro-3-iodo-1H-pyrazolo[4,3-c]pyridineTo a mixture of Intermediate 11 (5.8 g, 38 mmol) and KOH (8 g, 142 mmol) in dioxane (100 ml) at room temperature was added iodine (19g, 76 mmol). The reaction mixture was stirred at 750C for 4 h, and then allowed to cool to room temperature. The solution was diluted with saturated Na2S2O3 (aq), and the resulting precipitate was filtered and dried to give a yellow solid (4.1 g). The filtrate was left standing for 3 days and filtration of the resulting precipitate yielded a further 2.35 g of the product. Combined yield (6.45 g, 61percent). 1H NMR (400 MHz, DMSO-d6) delta ppm 7.64 (d, J=6.0 Hz, 1 H), 8.11 (d, J=6.0 Hz, 1 H); m/z (ES+APCI)+: 280 [M + H]+.
6.3 g With iodine; potassium hydroxide; In 1,2-dimethoxyethane; at 75℃; for 4h; C) 4-chloro-3-iodo-1H-pyrazolo[4,3-c]pyridine [1033] To a mixture of <strong>[871836-51-0]4-chloro-1H-pyrazolo[4,3-c]pyridine</strong> (4.0 g) and potassium hydroxide (4.4 g) in DME (50 mL) was added iodine (13.3 g) at room temperature. The reaction mixture was stirred at 75°C for 4 hr. The reaction mixture was added to aqueous sodium thiosulfate solution, and the mixture was left stand overnight, and the resulting solid was collected by filtration to give the title compound (6.3 g). MS(ESI+): [M+H]+ 279.9. MS(ESI+), found: 280.1.
1.57 g With iodine; potassium hydroxide; In 1,4-dioxane; at 75℃; for 4h; A solution of 4-chloro-lH-pyrazolo[4,3-c]pyridine (750.0 mg, 4.902 mmol, 1.0 eq), KOH (988.0 mg, 17.647 mmol, 4.0 eq) and 12 (2.49 g, 9.804 mmoL, 2.0 eq) in 1,4- dioxane (20.0 mL) was stirred at 75 °C for 4 h, then cooled and quenched by sat. aq. Na2S03 and the precipitate was collected by filtration to provide 4-chloro-3-iodo-lH- pyrazolo[4,3-c]pyridine (1.57 g).

 

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Technical Information

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