4-(3-Isopropylamino-2-hydroxypropoxy indene

#This invention relates to novel indene derivatives having valuable therapeutic properties, non-toxic salts thereof, and to processes for their production.

#The therapeutically active compounds of this invention are represented by the general formula ##STR2## wherein R represents a lower alkyl, phenylloweralkyl or lower cycloalkyl group.

#The term "lower alkyl" as used herein means both straight and branched chain aliphatic hydrocarbon groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, amyl, hexyl, etc. The term "phenylloweralkyl", which may contain more than one phenyl group, is represented by groups such as benzyl, diphenylmethyl, .beta.-phenylisopropyl, etc. The term "lower cycloalkyl" is represented by groups such as cyclopentyl and cyclohexyl, etc.

#a. A mixture of 0.9 g. of 4-hydroxyindene, 2.0 g. of 1,2-epoxy-3-chloropropane, 2.7 g. of potassium carbonate and 15 ml. of acetone was refluxed at about 57.degree. C. for 24 hours. Acetone was removed by vacuum distillation, the residue was washed with 10 ml. of water and then extracted with 20 ml. of ether three times. The ether extract was dried with magnesium sulfate, filtered and subjected to column chromatography using a column (having an inside diameter of about 3 cm. and a height of about 50 cm.) packed with silica gel. The 5th to 7th fractions (volume of one fraction is 50 ml.) recovered from the chromatographic column using chloroform as the effluent were combined together and concentrated to provide 0.6 g. of 4-(2,3-epoxypropoxy)indene.

#b. A mixture of 0.42 g. of 4-(2,3-epoxypropoxy)indene, 1.20 g. of isopropylamine and 20 ml. of methanol was stirred in a flask at room temperature for 2 hours. Methanol and unchanged isopropylamine were removed by vacuum distillation and the residue was recrystallized from a mixture of n-hexane and ether to yield 0.41 g. of 4-(3-isopropylamino-2-hydroxypropoxy)indene having a melting point of 88.degree.-89.degree. C.

#c. To a solution of 0.41 g. of 4-(3-isopropylamino-2-hydroxypropoxy)indene in 80 ml. of absolute ether there was added dropwise a hydrochloric acid-ether mixture at 0.degree. C. with stirring. The precipitates thus formed were recovered by filtration and recrystallized from a mixture of ethanol and ether to provide 0.44 g. of the hydrochloride of 4-(3-isopropylamino-2-hydroxypropoxy)indene. M.P. 147.degree.-148.degree. C.