N-(2-HYDROXY-5-(1-HYDROXY-2-(2-METHYL-1-PHENYLPROPAN-2-YLAMINO)ETHYL)PHENYL)METHANE

Originator

Zinterol Hydrochloride,ZYF Pharm Chemical

Uses

Zinterol is a β2-adrenergic agonist. It can be used to induce smooth muscle relaxation in the lungs, gastrointestinal tract, uterus, and various blood vessels.

Uses

Bronchodilator.

Manufacturing Process

A). 2'-Hydroxy-5'-([N-(2-methyl-1-phenyl-2-propyl)glycyl]methane- sulfonanilide hydrobromide:
To a solution of α,α-dimethylphenthylamine (120 g, 0.8 mole) in 1.1 liter of acetonitrile is added 5'-bromoacetyl-2'-hydroxymethanesulfonanilide (108 g, 0.35 mole) in a period of 5 minutes. The resulting solution is refluxed for 5 minutes on a steam bath and then permitted to stand for 25 minutes at room temperature after which it is chilled and acidified with 5 N ethanolic hydrogen bromide. The acidified mixture is concentrated in vacuum until a thick slurry is obtained. After standing overnight at room temperature, the slurry is filtered and the crude product triturated with 2-butanone, filtered, washed with 2- butanone and dried to 86.3 g, (54%), MP: 217.5-221°C (dec.).
B). 2'-Hydroxy-5'-(1-hydroxy-2-(2-methyl-1-phenyl-2-propylamino)ethyl) methanesulfonanilide hydrobromide:
2'-Hydroxy-5'-([N-(2-methyl-1-phenyl-2-propyl)glycyl]methanesulfonanilide hydrobromide (132 g, 0.29 mole is dissolved in 2 liters of hot methanol, the methanolic solution is allowed to cool to room temperature and 13 g 10% palladium on carbon catalyst suspended in 50 ml of water is added. Hydrogenation of the stirred mixture is carried out under 1-3 atm. of pressure for 17 hours during which time 0.31 mole of hydrogen is absorbed. The catalyst is filtered and the filtrate concentrated under reduced pressure until a thick slurry is obtained. Isoptopanpl is added tothed slurry and the mixture is again concentrated in vacuum to remove water by azeotropic distillation. Trituration of residual solid with 2-propanol and collection on a filter affords 100.5 g (76% yield) of desired product, MP: 194.5-195.5°C (dec.).
2'-Hydroxy-5'-(1-hydroxy-2-(2-methyl-1-phenyl-2-propylamino)ethyl) methanesulfonanilide base:
2'-Hydroxy-5'-(1-hydroxy-2-(2-methyl-1-phenyl-2-propylamino)ethyl)
methanesulfonanilide hydrobromide (47.7 g) is refluxed with 100 ml of methanol. The material only partly dissolves. A solution of 6.5 g of potassium hydroxide in 25 ml of methanol is then added to the suspension followed by 1 L of water. The mixture is thoroughly stirred and cooled to 5-10°C. The precipitate is collected on a filter and washed with water until a negative test for bromide using silver nitrate is obtained. The product is dried in an oven at 65°C, yield 36 g.

Therapeutic Function

Bronchodilator

Biological Activity

Potent and selective β 2 -adrenoceptor agonist (pK B values are 8.3 and < 5.7 for β 2 and β 1 receptors respectively, as measured in human artery).

Raw materials

Preparation Products