BMS-243117

N-(2-氯-6-甲基苯基)-2-[[(叔丁基氨基)羰基]氨基]-6-苯并噻唑甲酰胺Chemical Name: 2-(3-tert-Butylureido)-N-(2-chloro-6-methylphenyl)benzothiazole-6-carboxamide
CAS No. 225521-80-2
项目整合开发状态: Biological Testing
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:Reaction of ethyl 4-aminobenzoate (I) with sodium thiocyanate and bromine in cold AcOH gives rise to the amino benzothiazole (II).Subsequent treatment of (II) with phenyl chloroformate affords the phenyl carbamate (III),which is further reacted with tert-butylamine to furnish urea (IV).After alkaline hydrolysis of the ethyl ester (IV),the resultant carboxylic acid (V) is converted to the azabenzotriazolyl active ester (VI) upon treatment with HATU in DMF.Active ester (VI) is finally coupled with 2-chloro-6-methylaniline (VII) in the presence of sodium bis(trimethylsilyl)amide to yield the target amide.

合成路线:In an alternative method,ethyl 4-aminobenzoate (I) is treated with NaSCN/Br2 to produce the amino benzothiazole (II),which is further protected as the N-Boc derivative (III).Alkaline hydrolysis of ester (III),followed by chlorination of the resultant acid (IV) with oxalyl chloride gives rise to the acid chloride (V).This is then coupled with 2-chloro-6-methylaniline (VI) yielding amide (VII).The N-Boc protecting group of (VII) is then cleaved employing trifluoroacetic acid to produce amine (VIII),which is subsequently reacted with phenyl chloroformate producing the phenyl carbamate (IX).Finally,displacement of carbamate (IX) with tert-butylamine furnishes the title urea.(1,2)