Aryl-Substituted Tetrahydropyrans

摘要

1,169,014. Tetrahydropyran derivatives. A. H. ROBINS CO. Inc. 20 Oct., 1966 [24 Oct., 1965], No. 47023/66. Heading C2C. The invention comprises (a) tetrahydropyran- 3-amines of Formula I, in which Ar is phenyl, C 1-8 alkyl-phenyl, hydroxyphenyl, C 1-8 alkoxyphenyl, halophenyl, trifluoromethylphenyl, or naphthyl, -NRR1 is amino, C 1-8 alkylamino, di-(C 1-8 alkyl) amino, phenylamino, (phenyl- C 1-8 alkyl) amino, di-(phenyl-C 1-8 alkyl) -amino, C 3-9 cycloalkylamino, di-(3 3-9 cycloalkyl)-amino, C 1-8 hydroxyalkyl-amino, di-(C 1-8 hydroxyalkyl) - amino, N - alkyl - N - C 1-8 hydroxyalkylamino or an unsubstituted or substituted saturated monocyclic or heterocyolio radical having up to 12 carbon atoms and up to 2 hetero atoms in the ring, and R is hydrogen or C 1-8 alkyl; (b) acid addition and quaternary ammonium salts of compounds I; (c) acylated tetrahydropyran-3-amines of Formula II, in which Ar and R11 are as defined above, R is hydrogen, C 1-8 alkyl, phenyl, phenyl- C 1-8 alkyl, C 3-9 cycloalkyl or C 1-8 hydroxyalkyl and R111 is C 1-8 alkyl, C 1-8 alkoxy, phenyl-C 1-8 - alkyl, C 1-8 alkylamino, di-(C 1-8 alkyl) amino, phenylamino, diphenylamino, C 3-9 cycloalkylamino, di-(C 3-9 cycloalkyl) amino, (phenyl-C 1-8 alkyl) amino or di-(phenyl-C 1-8 alkyl) amino; (d) the preparation of Compounds I by reacting together for 5 to 100 hours at 110‹ to 190‹ C., a compound of Formula III, in which X is bromine or chlorine, and a compound of formula HNRR1; and (e) the preparation of compounds II by reacting a compound I with a compound of formula Cl.COR111 or (R111CO) 2 O or with phenyl isocyanate. 3 - Bromo - 2 - phenyltetrahydropyran is prepared by reacting dihydropyran with bromine followed by phenyl magnesium bromide. 3 - Bromo - 2 - (3 - methoxyphenyl) - tetrahydropyran, 3 - bromo - 2 - (1 - naphthyl) - tetrahydropyran, 3 - bromo - 2 - (3 - trifluoromethylphenyl)- tetrahydropyran, 3 - bromo - 2 - p - tolyltetrahydropyran and 3 - bromo - 4 - methyl - 2 - phenyltetrahydropyran are similarly prepared. Pharmaceutical compositions having vasopressor, central nervous system stimulant, antidepressant, appetite suppressant, nasal decongestant and/or sedative activity, comprise a compound of Formula I or II, or a pharmaceutically acceptable acid addition or quaternary ammonium salt of a compound I, together with a pharmaceutical carrier. The compositions may be administered orally or parenterally.