Patent GB-1268239-A (GB)
Title: Tricycloundecane derivatives
Inventor: BEREZIN G H
IPC: C07D205/04
Filed: 1969-09-08
Abstract: 1,268,239. Tricycloundecane derivatives. E.I. DU PONT DE NEMOURS & CO. 8 Sept., 1969 [9 Sept., 1968; 31 July, 1969], No. 44373/69. Heading C2C. [Also in Division C5] Novel compounds I in which Q has Formula II n is 0 or 1; R<SP>1</SP> and R<SP>2</SP> are H or 1-2C alkyl; R 3  is H, 1-4C alkyl, 3-9C alkenyl, 3-methyl-2- methylene - 3 - butenyl, 5-8C cycloalkenyl, 6-9C alkenylcycloalkyl, 6-9C cycloalkylalkenyl, 3-5C alkynyl, or benzyl and R 4  is H, 1-3C alkyl, 3-5C alkenyl or propargyl or R 3  and R 4  together form a divalent organic radical subject to the proviso that any unsaturation in R 3  and R 4  is not in the 1-position and salts thereof are prepared by (a) reducing compounds III in which A is a group capable of being reduced to NH 2  or -CH(R<SP>2</SP>)NH 2 ; (b) reductively aminating a compound III in which A is a group or atom capable of being reductively aminated to a group (c) reductively aminating with NH 3  tricycloundecan-4-ane to give I where n is 0 and R 1 , R 3  and R 4  are all H (d) reacting a compound IV where X is a leaving group with an amine donor (e) reducing a compound V where R<SP>4</SP> and R<SP>5</SP> are H or 1-3C alkyl (f) converting the amino group in I into a different amino group by known methods or (g) hydrolysing a compound VI Spiro[ozirane - 2,2<SP>1</SP>-tricyclo(3.3.1.1<SP>3,7</SP>)]-decane is prepared by oxidation of 2-methyleneadamantane. Adamantane cyanohydrin is prepared by reaction of adamantanone with NaCN. 2 - Aminomethyl - 2 - adamantanol is prepared by reaction of adamantane cyanohydrin with LiAlH 4  or by reaction of the above spiro intermediate with NH 3  in a stainless steel bomb. Novel tricyclo(4.3.1.1.<SP>3,8</SP>)undecan-4-one is prepared by reaction of 2-amino-methyl-2-adamantanol with NaNO 2  and glacial acetic acid. Tricyclo(4.3.1.1.<SP>3,8</SP>)undecan - 4 - one - oxime is prepared by reaction of the 4-one with hydroxylamine HCl. 4 - Formamido - tricyclo(4.3.1.1<SP>3,8</SP>) - undecane is prepared by reaction of the appropriate 4- amino compound with butyl formate. Similarly prepared are 4-formamidomethyl-; 4-methyl-4- formamidomethyl; α - methyl - 4 - formamidomethyl- and N - formyl - N - methyl - 4 - aminomethyl-tricyclo(4.3.1.1.<SP>3,8</SP>)-undecane. N - acetyl - tricyclo(4.3.1.1<SP>3,8</SP>)undecane - 4- amine is prepared by acetylation of the appropriate amine. Similarly prepared are N-acetyl- N - methyl - 4 - amino- ; N - acetyl - N - methyl- 4 - amino - methyl-; N - acetyl - α - methyl - 4- aminomethyl-; N - acetyl N - methyl - 4 - amino- 4 - ethyl-; N - acetyl - N - benzyl - 4 - aminomethyl- and N - acetyl - N - (3 - cyclohexenyl)- 4 - aminomethyl - tricyclo(4.3.1.1.<SP>3,8</SP>) - undecane. 4 - Ethyl - 4 - hydroxy - tricyclo(4.3.1.1<SP>3,8</SP>)- undecane is prepared by reaction of the 4-one with ethyl lithium. The 4-methyl derivative may be similarly prepared. Tricyclo(4.3.1.1.<SP>3,8</SP>)undecan - 4 - ol is prepared by reduction of the 4-one with LiAlH 4 . 4 . Bromo - tricyclo(4.3.1.1<SP>3,8</SP>)undecane is prepared by reaction of the 4-ol with Br 2 . 4 - Methylene - tricyclo(4.3.1.1<SP>3,8</SP>)undecane is prepared by reaction of the 4-one with methyl triphenylphosphonium bromide. 4 - Hydroxymethyl - tricyclo(4.3.1.1<SP>3,8</SP>)undecane is prepared from the 4-methylene derivative by reaction with H 2 O 2 . Tricyclo(4.3.1.1<SP>3,8</SP>)undecane - 4 - carboxylic acid is prepared by oxidation of the 4-hydroxymethyl derivative. The corresponding acid chloride is prepared by conventional methods and converted to the 4-carboxamide by reaction with NH 3 . Similarly prepared are the N-allyl-; N - (1,1 - dimethylallyl)-; N - (3 - methylenecyclobutylmethyl)-; N - (2 - methallyl)- and N- (3 methylenecyclobutyl) - carboxamide derivatives and 3 - methylene - 1 - [tricyclo(4.3.1.1.<SP>3,8</SP>)undecan - 4 - yl . carbonyl] - azetidine. 4 - Cyano - tricyclo(4.3.1.1<SP>3,8</SP>) - undecane is prepared by reaction of the 4-carboxamide derivative with SOCl 2  or by reaction of the 4- bromo derivative with NaCN. Methyl - 4 - tricyclo(4.3.1.1.<SP>3,8</SP>)undecyl ketone is prepared by reaction of the 4 cyano derivative with methyl magnesium bromide. Pharmaceutical compositions comprise a compound I together with a suitable excipient for oral or parenteral administration as anti-viral agents.