A PROCESS FOR THE SYNTHESIS OF 5-(N-ETHYL-N-2-HYDROXY ETHYLAMINO)-2-PENTYL AMINE (HYDROXY NOVOLDAMINE), 5-N,N-DIETHYLAMINO)-2-PENTYLAMINE(NOVOLDAMINE)

摘要

A process for the synthesis of 5-(N-ethyl-N-2-hydroxyethylamino)-2-pentylamine (Hydroxy Novoldamine), 5-(N,N-diethylamino)-2-pentylamine(Novoldamine) wherein the said process comprises a) ketalization of 1-chloro-4-pentanone carried out by treating it with glycol selected from ethylene glycol or neopentyl glycol in a molar ratio of 1:2 in presence of non polar organic solvent selected from toluene, cyclohexane, xylene, heptane and hexane and catalyst selected from para-toluene sulphonic acid, methane sulphonic acid, perchloric acid at temperature range of 80-140°C for 20-25 hours to obtain compound of formula (I) 2(3'-chloropropyl)2-methyl-1,3-dioxalane, 2-(3 '-chloropropyl) -2,5,5-Trimethyl 1,3-dioxane; 0) b) condensation of said compound of formula (I) 2(3'-chloropropyl)2-methyl- 1,3-dioxalane, 2-(3'-chIoropropyl) -2,5,5-Trimethyl 1,3-dioxane with substituted amine derivatives of formula (V) N-ethyl-N-2-hydroxy ethyl amine, N,N-diethylamine in a molar ratio of 2:5 in presence of non-polar solvents selected from toluene, xylene and cyclohexane at temperature ranging from 90°C-140°C for 18 hours to obtain compound of formula (II) 2-(3' -N-ethy 1- N-2-hydroxyethylaminopropyl)-2-methyl-1,3 -dioxalane (HNK Ketal); 3 H 1 NR2 R1=R2=Ethyl or R1R2=Ethyl Rl=Ethyl; R1 =Ethyl R2=Hydroxy ethyl (11) (V) c) deprotection of the ketal group of compound of formula (II), 2-(3,-N-ethyI-N-2-hydroxyethylaminopropyl)-2-methyl-l,3-dioxalane (HNK Ketal) under acidic conditions at temperature range of 10- 50°C for 6-7 hours to obtain compound of formula (III) 5-(N-ethyl-N-2-hyd^xyethylamino)-4-pentanone or 5-(N.N-diethylamino)-4-pentanone; and 0 NT Ri = R2 = Ethyl (or) R1=Ethyl; R2=Hydroxy ethyl d) reductive amination of compound of formula (III), 5-(N-ethyl-N-2-hydroxyethylamino)-4-pentanone or 5-(N,N-diethylamino)-4-pentanone is carried out by treating it with alcoholic ammonia in presence of catalyst such as Raney Nickel under mild hydrogenation conditions such as 10-30 kg/cm2 and temperature ranging from 40-130°C for 2-5 hours to yield compound of formula (IV) namely 5-(N-ethyl-N-2-hydroxyethylamino)-2-pentylamine and 5-(N,N'diethyIamino)-2-pentylamine. 10 (IV) i)Ri ,R2= Ethyl—- 5-[N,N-diethylamino]-2-pentylamine] ii) R, = Ethyl, R2 = hydroxy ethyl —*■ 5-[N-ethyl-N-2-hydroxyethylamino]-2-pent