Bosentan synthesis

7synthesis methods

Product Name:Bosentan
CAS Number:147536-97-8
Molecular formula:C27H29N5O6S
Molecular Weight:551.61

Bosentan is a mixed Endothelin Receptor Antagonist which is used as a vasodilator. Bosentan is an inhibitor of ETAR and ETBR. It is used for the treatment of pulmonary artery hypertension (PAH). Bosentan blocks the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure.

Synthetic Routes

ROUTE 1

ROUTE 2

ROUTE 3

ROUTE 4

ROUTE 5

ROUTE 6

ROUTE 7

ROUTE 8

ROUTE 9

ROUTE 10

Raju, K. Rajasekhara; Reddy, B. Shankar; Somannavar, Y. S.; Sinha, B. K.; Babu, P. N. Kishore; Raju, K. Mohana. Improved Large-Scale Synthesis of Bosentan Monohydrate. Organic Preparations and Procedures International. Chemical Research and Development. Aurobindo Pharma Ltd. Telangana, India. Volume 48. Issue 6. Pages 481-491. 2016

107-21-1 Synthesis

107-21-1
1317 suppliers
$10.00/25g

4-tert-Butyl-N-(6-chloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl)benzenesulfonamide

150727-06-3
158 suppliers
$17.00/100mg

147536-97-8
237 suppliers
$29.00/5mg

Yield:147536-97-8 95.7%

Reaction Conditions:

Stage #1: ethylene glycol;4-tert-butyl-N-(6-chloro-5-(2-methoxyphenoxy)2,2'-bipyrimidin-4-yl)benzene sulfonamidewith sodium hydroxide in tetrahydrofuran at 60 - 65; for 12 h;
Stage #2: with tartaric acid in tetrahydrofuran;water at 5 - 10; for 1 h;

Steps:

8

Example 8: Preparation of crude Bosentan from compound of formula Via.The compound of formula Via (130.0g, 1.0eq), ethylene glycol (1470.0ml,107.0eq) and sodium hydroxide (88.9g, 9.0eq) were heated in tetrahydrofuran (1560.0ml,12.0vol) at 60- 65°C for 12hours. After completion of reaction, the reaction mixture was added to a mixture of water (4450.0ml,35.0vol) and DL-Tartaric acid (185.0g, 5.0eq) at 5-10°C. Maintained at this temperature for 1 hour. Filtered the solid and washed with water (1300.0ml). Dried the solid, Bosentan, under vacuum at 50-55°C for 12 hours to get the title compound (Yield: 134.5g (95.7%, HPLC purity 98.41 %).

References:

WO2012/56468,2012,A1 Location in patent:Page/Page column 16

Benzenesulfonamide, 4-(1,1-dimethylethyl)-N-[6-(2-hydroxyethoxy)-2-iodo-5-(2-methoxyphenoxy)-4-pyrimidinyl]-

1206769-86-9
1 suppliers
inquiry

153435-63-3
107 suppliers
$35.00/250mg

147536-97-8
237 suppliers
$29.00/5mg

References

Benzenesulfonamide, N-[2-bromo-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-4-pyrimidinyl]-4-(1,1-dimethylethyl)-

1206769-81-4
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inquiry

153435-63-3
107 suppliers
$35.00/250mg

147536-97-8
237 suppliers
$29.00/5mg

References

Potassium ((4-(tert-butyl)phenyl)sulfonyl)(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-[2,2''-bipyrimidin]-4-yl)amide

1174918-31-0
1 suppliers
inquiry

147536-97-8
237 suppliers
$29.00/5mg

References

trifluoromethanesulfonic acid 4-(2-tert-butoxyethoxy)-6-(4-tert-butylbenzenesulfonylamino)-5-(2-methoxyphenoxy)pyrimidin-2-yl ester

1334686-05-3
1 suppliers
inquiry

153435-63-3
107 suppliers
$35.00/250mg

147536-97-8
237 suppliers
$29.00/5mg

References

Bosentan Related Search:

Anisole Ethoxyquin p-Anisaldehyde 4-Methoxybenzyl cyanide 4-Methoxyphenol Guaiacol p-Anisidine 2-Cyanopyrimidine 5-(2-Methoxyphenoxy)-[2,2'-bipyrimidine]-4,6(1H,5H)-dione Bosentan Impurity 1