Basic information Safety Supplier Related
ChemicalBook >  Product Catalog >  Pharmaceutical intermediates >  Heterocyclic compound >  (E)-6-Iodo-3-[2-(pyridin-2-yl)ethenyl]-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

(E)-6-Iodo-3-[2-(pyridin-2-yl)ethenyl]-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Basic information Safety Supplier Related

(E)-6-Iodo-3-[2-(pyridin-2-yl)ethenyl]-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole Basic information

Product Name:
(E)-6-Iodo-3-[2-(pyridin-2-yl)ethenyl]-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole
Synonyms:
  • (E)-6-Iodo-3-[2-(pyridin-2-yl)ethenyl]-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole
  • 6-Iodo-3-[(1E)-2-(2-pyridinyl)ethenyl]-1-(tetrahydro-2H-pyran-2-yl)-1H-Indazole
  • (E)-6-iodo-3-(2-(pyridin-2-yl)vinyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole
  • (E)-6-iodo-3-(2-(pyridin-2-yl)vinyl)-1-(tetrahydro-2H-pyran-2-yl)
  • 6-iodo-3-((E)-2-(pyridin-2-yl-vinyl) -1-(tetrahydropyran-2-yl)-1H-indazole
  • 6-iodo-1-(oxan-2-yl)-3-(2-pyridin-2-ylethenyl)indazole
  • 6-Iodo-3-(2-pyridin-2-yl-vinyl)-1-(tetrahydro-pyran-2-yl)-1H-indazole
  • 1H-Indazole, 6-iodo-3-[(1E)-2-(2-pyridinyl)ethenyl]-1-(tetrahydro-2H-pyran-2-yl)-
CAS:
886230-77-9
MF:
C19H18IN3O
MW:
431.27
EINECS:
1312995-182-4
Product Categories:
  • Intermediate of Axitinib
  • intermediate
Mol File:
886230-77-9.mol
More
Less

(E)-6-Iodo-3-[2-(pyridin-2-yl)ethenyl]-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole Chemical Properties

Melting point:
156-159°C
Boiling point:
561.2±50.0 °C(Predicted)
Density 
1.60
storage temp. 
2-8°C(protect from light)
solubility 
Chloroform, DMSO, Methanol
pka
4.25±0.10(Predicted)
form 
Solid
color 
Light Yellow
Stability:
Hygroscopic, Light Sensitive
InChI
InChI=1S/C19H18IN3O/c20-14-7-9-16-17(10-8-15-5-1-3-11-21-15)22-23(18(16)13-14)19-6-2-4-12-24-19/h1,3,5,7-11,13,19H,2,4,6,12H2/b10-8+
InChIKey
QXJFRDDGGSSQDX-CSKARUKUSA-N
SMILES
N1(C2OCCCC2)C2=C(C=CC(I)=C2)C(/C=C/C2=NC=CC=C2)=N1
More
Less

(E)-6-Iodo-3-[2-(pyridin-2-yl)ethenyl]-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole Usage And Synthesis

Uses

(E)-6-Iodo-3-[2-(pyridin-2-yl)ethenyl]-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole is an intermediate used to prepare Axitinib (A794650) . Axitinib is used in cancer therapy. Axitinib (AG-013736) is a selective small molecule inhibitor of VEGF receptor tyrosine kinases 1, 2 and 3 and the platelet-derived growth factor (PDGF) receptor that targets the catalytic domain of the tyrosine kinase and induces ATP-competitive inhibition with limited activity against other protein kinases . It is an indazole derivative, its molecular formula is C22H18N4OS and its molecular weight is 386.5 Da[1].

Synthesis

6-amino-3-((E)-2-pyridin-2-yl-vinyl)-1-(tetrahydropyran-2-yl)-1 H-indazole (100 g) dissolved in acetic acid (6.5 L) is added over 1.5 hours to a solution of sodium nitrite (35 g) dissolved in water (3.0 L) at 0℃ (-3 ± 3°C). The mixture is stirred for 1 hour at 0℃, and a solution of hydrochloric acid (560 mL diluted in 1 L of water) at 0℃ is added over 15 minutes. The mixture is stirred for 1 hour at 0℃. The formation of the diazonium salt is monitored by HPLC. Dicholoromethane (400 ml) at O0C is added over 10 minutes to the diazonium salt solution at 0℃, and a solution of potassium iodide (207. 25 g) dissolved in water (300 ml) at O0C is added over 1.5 hours. The reaction mixture is agitated for 3 hours at 0℃ (until complete by HPLC). The mixture is then poured into a solution of sodium bisulfite in process water [Sodium bisulfite (200g) dissolve in process water (500mL) at 27± 3°C] and Dicholoromethane (400 ml) below 270C, agitated, and the layers separated. The aqueous layer is extracted with Dichloromethane (100 ml) at 27℃ and combined. A solution of aqueous ammonia (100 ml) at 27± 3°C is added over 40 minutes to the combined organic layers until the aqueous phase is basic (pH = 9 to 12). Distill out dichloromethane and add methanol and heat to 50 ± 3°C and stir it at this temperature for 15 min and then stir for 30 min at RT, followed by washing with methanol. Add dichloromethane and heat to 45± 3°C and add activated carbon at this temperature. Followed by addition of methanol and dichloromethane (if required) and stir the reaction mixture at 27± 3°C for 30 min and cool it to 0±3°C and stir 1 hr and wash with methanol to provide (E)-6-Iodo-3-[2- (pyridine-2yl)ethenyl]-1 -(tetrahydro-2H- pyran-2-yl)-1H-indazole.

References

[1] LESLIEISLA. Avelumab and axitinib in the treatment of renal cell carcinoma: safety and efficacy.[J]. Expert Review of Anticancer Therapy, 2020, 20 5: 343-354. DOI:10.1080/14737140.2020.1756780.

(E)-6-Iodo-3-[2-(pyridin-2-yl)ethenyl]-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleSupplier

Shanghai Kuanghao Chemistry Technology Co., Ltd. Gold
Tel
13130049594 13130049594
Email
83219210@qq.com
Jinan XinKe Pharmaceutical Technology Co., Ltd. Gold
Tel
0531-88259693 17854196142
Email
2820602043@qq.com
ZHIWE CHEMTECH CO LTD
Tel
021-20221225 13917446399
Email
sales@zhiwe.net
Beijing HwrkChemical Technology Co., Ltd
Tel
010-89508211 18501085097
Email
sales.bj@hwrkchemical.com
BeiJing Hwrk Chemicals Limted
Tel
0757-86329057 18934348241
Email
sales4.gd@hwrkchemical.com