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Chemical Structure| 1357945-27-7 Chemical Structure| 1357945-27-7
Chemical Structure| 1357945-27-7

*Storage: Keep in dark place,Inert atmosphere,2-8°C.

5-Chloro-3-iodo-1H-pyrazolo[4,3-b]pyridine

CAS No.: 1357945-27-7

4.5 *For Research Use Only !

Cat. No.: A172747 Purity: 95%

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Product Details of [ 1357945-27-7 ]

CAS No. :1357945-27-7
Formula : C6H3ClIN3
M.W : 279.47
SMILES Code : IC1=NNC2=CC=C(Cl)N=C21
MDL No. :MFCD16658104
InChI Key :GJYMAUPNXHZFIU-UHFFFAOYSA-N
Pubchem ID :71700022

Safety of [ 1357945-27-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H320-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Calculated chemistry of [ 1357945-27-7 ] 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.

1.3
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

2.22
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

2.12

Water Solubility

Log S (ESOL):?

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

-3.58
Solubility 0.0741 mg/ml ; 0.000265 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.

-2.73
Solubility 0.523 mg/ml ; 0.00187 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.

-6.43 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)

2.22

Application In Synthesis [ 1357945-27-7 ]

* 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.

  • Upstream synthesis route of [ 1357945-27-7 ]

[ 1357945-27-7 ] Synthesis Path-Upstream   1~3

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  • [ 1357945-27-7 ]
YieldReaction ConditionsOperation in experiment
99.3% With iodine; potassium hydroxide In N,N-dimethyl-formamide at 25℃; Cooling with ice To a solution of 5-chloro-1H-pyrazolo[4,3-bjpyridine (XIII) (13 g, 84.7 mmol) in DMF (100 mL) was added iodine (43.0 g, 169 mmol) followed by potassium hydroxide powder (23.75 g, 423 mmol) portion wise under ice water cooling. The reaction mixture was stirred at 25°C overnight. The solid KOH was filtered off, washed with EtOAc, most of the DMF was removed under vacuum and the residue was diluted with water (200 mL) and extracted with 5 X 200 mL EtOAc, washed with brine (500 mL), dried over Na2504 and concentrated to give 5- chloro-3-iodo-1H-pyrazolo[4,3-bjpyridine (XIV) as an orange solid (23.5 g, 84.1 mmol, 99.3 percent yield). ESIMS found for C6H3C1TN3 mlz 279.9 (M+H).
99.3% With iodine In N,N-dimethyl-formamide at 25℃; for 12 h; Cooling with ice j0607j To a solution of 5-chloro-1H-pyrazolo[4,3-bjpyridine (XIII) (13 g, 84.7 mmol) in DMF (100 mL) was added iodine (43.0 g, 169 mmol) followed by potassium hydroxide powder (23.75 g, 423 mmol) portion wise under ice water cooling. The reaction mixture was stirred at 25°C overnight. The solid KOH was filtered off, washed with EtOAc, most of the DMF was removed under vacuum and the residue was diluted with water (200 mL) and extracted with EtOAc (5 x 200 mL), washed with brine (500 mL), dried over Na2504 and concentrated to give 5-chloro- 3-iodo-1H-pyrazolo[4,3-bjpyridine (XIV) as an orange solid (23.5 g, 84.1 mmol, 99.3 percent yield). ESIMS found for C6H3C1TN3 mlz 279.9 (M+H).
99.3% With iodine; potassium hydroxide In N,N-dimethyl-formamide at 25℃; To a solution of 5-chloro-lH-pyrazolo[4,3-b]pyridine (XIII) (13 g, 84.7 mmol) in DMF (100 mL) was added iodine (43.0 g, 169 mmol) followed by potassium hydroxide powder (23.75 g, 423 mmol) portion wise under ice water cooling. The reaction mixture was stirred at 25 °C overnight. The solid KOH was filtered off, washed with EtOAc, most of the DMF was removed under vacuum and the residue was diluted with water (200 mL) and extracted with EtOAc (5 x 200 mL), washed with brine (500 mL), dried over Na2SC>4 and concentrated to give 5-chloro- 3-iodo-lH-pyrazolo[4,3-b]pyridine (XIV) as an orange solid (23.5 g, 84.1 mmol, 99.3 percent yield). ESIMS found for C6H3C1IN3 mlz 279.9 (M+H).
99.3% With iodine; potassium hydroxide In N,N-dimethyl-formamide at 25℃; [0607] To a solution of 5-chloro-lH-pyrazolo[4,3-b]pyridine (XIII) (13 g, 84.7 mmol) in DMF (100 mL) was added iodine (43.0 g, 169 mmol) followed by potassium hydroxide powder (23.75 g, 423 mmol) portion wise under ice water cooling. The reaction mixture was stirred at 25°C overnight. The solid KOH was filtered off, washed with EtOAc, most of the DMF was removed under vacuum and the residue was diluted with water (200 mL) and extracted with EtOAc (5 x 200 mL), washed with brine (500 mL), dried over Na2S04 and concentrated to give 5-chloro- 3-iodo-lH-pyrazolo[4,3-b]pyridine (XIV) as an orange solid (23.5 g, 84.1 mmol, 99.3 percent yield). ESIMS found for C6H3C1IN3 mlz 279.9 (M+H).
91% With iodine; sodium hydroxide In 1,4-dioxane at 90℃; for 18 h; The mixture of 5-chloro-1H-pyrazolo [4, 3-b] pyridine (2.0 g, 13.02 mmol) , iodine (13.0 g, 52.1 mmol) and NaOH (12M, 11 mL, 130 mmol) in dioxane (20 mL) was stirred at 90 for 18 h. The reaction mixture was cooled to room temperature and extracted with ethyl acetate (20 mL x3) . The combined organic layers were washed with 10percentaqueous Na2S2O3(20 mLx2) , brine (20 mL) , dried over anhydrous Na2SO4, filtered off, and concentrated in vacuo. The crude product was purified by silica gel flash column chromatography eluting with hexanes/ethyl acetate (4: 11: 1) to give the title compound (3.3 g, 91percentyield) .
86% With N-iodo-succinimide In N,N-dimethyl-formamide at 20℃; Inert atmosphere 5-Chloro-1 H-pyrazolo[4,3-/ ]pyridine (Preparation 1 a, 13.4 g, 0.09 mol) was dissolved in N,N- dimethylformamide (250 mL) and A/-iodosuccinimide (22.5 g, 0.10 mol) was added portionwise under argon atmosphere. The reaction mixture was stirred at room temperature overnight. Then more A/-iodosuccinimide (8.0 g) was added and the reaction was stirred at room temperature for 48 hours. The solvent was removed and the crude was suspended in water and extracted with ethyl acetate (x3). The combined organics were washed with a 10percent sodium thiosulfate aqueous saturated solution, water and brine, dried over anhydrous magnesium sulphate and concentrated under reduced pressure to yield the title compound (20.8 g, 86percent) as a solid. LRMS (m/z): 280, 282 (M+1 , M+3)+. -NMR δ (300 MHz, DMSO-d6): 7.49 (d, 1 H), 8.1 1 (d, 1 H).

References: [1] Patent: WO2017/23989, 2017, A1, . Location in patent: Paragraph 0606; 0607.
[2] Patent: WO2017/23972, 2017, A1, . Location in patent: Paragraph 0606; 0607.
[3] Patent: WO2017/24015, 2017, A1, . Location in patent: Paragraph 006.
[4] Patent: WO2017/23988, 2017, A1, . Location in patent: Paragraph 0607.
[5] Patent: WO2019/37640, 2019, A1, . Location in patent: Page/Page column 70.
[6] Patent: WO2017/220431, 2017, A1, . Location in patent: Page/Page column 36; 37.
[7] Patent: US2018/72718, 2018, A1, . Location in patent: Paragraph 0394; 0395.
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References: [1] Patent: WO2017/35353, 2017, A1, . Location in patent: Paragraph 0533.
  • 3
  • [ 164666-68-6 ]
  • [ 1357945-27-7 ]
References: [1] Patent: WO2017/220431, 2017, A1, .
 

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