Ladostigil tartrate, TV-3219(racemic, HCl), TV-3326

乙基甲基-氨基甲酸 (3R)-2,3-二氢-3-(2-丙炔氨基)-1H-茚-5-基酯酒石酸盐Chemical Name: N-Ethyl-N-methylcarbamic acid 3(R)-(2-propynylamino)-2,3-dihydro-1H-inden-5-yl ester L-tartrate
CAS No. 209394-46-7, 209394-27-4 (free base), 209394-47-8 (monoethanesulfonate), 209394-39-8 (monofumarate), 209394-18-3 (monoHCl), 209394-28-5 (monomethanesulfonate)
项目整合开发状态: Phase I
项目研究机构: Hebrew University (Originator), Teva (Licensee)
合成路线:Treatment of (R)-1-aminoindan (I) with trifluoroacetic anhydride in toluene affords trifluoroacetyl derivative (II),which is condensed with chloroacetyl chloride (III) by means of AlCl3 in 1,2-dichloroethane to provide compound (IV).Oxidation of chloroacetyl derivative (IV) with 3-chloroperoxybenzoic acid (mCPBA) and TFA in CH2Cl2 allows formation of chloroacetoxy (V),which is converted into the hydroxy form (VI) by heating in hot methanol/H2O in the presence of K2CO3.N-Protection of (VI) is then performed by treatment with di-t-butyl dicarbonate and Et3N in THF to furnish Boc derivative (VII),which is then converted into derivative (IX) by O-acylation with N-Me,N-Et carbamoyl chloride (VIII) by means of NaH in acetonitrile.Removal of the Boc group of (IX) by treatment with HCl (gas) in dioxane gives hydrochloride (X),which is finally N-alkylated with propargyl bromide (XI) by means of K2CO3 in acetonitrile to yield the desired product.