TA-0201, T-0201

Chemical Name: N-[6-[2-(5-Bromopyridin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl]-4-(2-hydroxy-1,1-dimethylethyl)benzenesulfonamide monosodium salt sesquihydrate
项目整合开发状态: Clinical
项目研究机构: Tanabe Seiyaku (Originator)
合成路线:Ethyl phenylacetate (I) was alkylated with two equivalents of methyl iodide in the presence of potassium tert-butoxide to yield 2-methyl-2-phenylpropionic ester (II),which was reduced to alcohol (III) with LiAlH4.The alcohol function of (III) was esterified with Ac2O in pyridine,and the resulting compound (IV) was converted to sulfonyl chloride (V) by sulfonation with H2SO4,followed by treatment with SOCl2.Further reaction of (V) with ammonium hydroxide yielded sulfonamide (VI).Condensation of this sulfonamide with the dichloropyrimidine (VII) furnished,after saponification with NaOH,the N-pyrimidinylsulfonamide (VIII)).The alcohol function of (VIII) was then protected as the tetrahydropyranyl ether with dihydropyran and camphorsulfonic acid,and further treatment with the sodium salt of ethylene glycol at 100 C yielded the (2-hydroxyethoxy)pyrimidine (IX).Condensation of (IX) with 5-bromo-2-chloropyrimidine (X) in the presence of NaH gave (XI),which was finally converted to the target compound by acid deprotection of the tetrahydropyranyl acetal,followed by formation of the sodium salt with NaOMe in THF-MeOH.