Patent GB-1470803-A (GB)
Title: 4h-s-triazolo-4,3-a 1,5-benzodiazepin-5-ones
IPC: C07C233/13
Filed: 1974-05-17
Abstract: 1470803 4H - 1,2,4 - triazolo[4,3-a][1,4]- benzodiazepin - 5 - ones E R SQUIBB & SONS Inc 17 May 1974 [29 May 1973] 22095/74 Heading C2C Novel compounds I in which R<SP>1</SP> is H, phenyl (optionally substituted by X), pyridyl, C 3-5  cycloalkyl or C 1-4  alkyl [optionally substituted by NH 2 , mono- or di- C 1-4  alkylamino, NO 2 , CN, OH, C 1-4  alkoxy, C 1-4  alkanoyloxy phenyl (optionally substituted by one or more X groups) or a group II in which D is CH 2 , O or NH<SP>10</SP> [where R<SP>10</SP> is H, C 1-4  alkyl or phenyl (optionally substituted by X)] and p and q are 1 to 3], R<SP>2</SP> is H, C 1-4  alkyl (optionally substituted by NH 2 , mono- or di- C 1-4  alkylamino or a group II) OH, C 1-6  alkoxy, or R<SP>5</SP>-COO [where R<SP>5</SP> is C 1-4  alkyl, phenyl (optionally substituted by X) or phenyl C 1-5  alkyl (in which the phenyl moiety is optionally substituted by X)], each X and Y is the same or different and is F, Cl, Br, CF 3 , C 1-6  alkyl C 1-6  alkoxy, NO 2 , CN, NH 2 , C 1-4  alkanoylamino, C 1-6  alkylthio, C 1-6  alkylsulphinyl or C 1-6  alkylsulphonyl, each R is independently 0 to 2 and m is 0 or 1 are prepared by reacting a compound 4 in which Z is NH.NH 2  or NH.NH.COOR<SP>4</SP> (where R<SP>4</SP> is t-Bu or benzyl optionally substituted on the phenyl ring by 1 to 3 X groups) with an acyl derivative R<SP>1</SP>-CO-W (where W is C 1-4  alkoxy, halogen, OH or -OCOR<SP>1</SP>). Compounds I are also prepared by reacting a compound 3 or a compound 4 where Z is SR<SP>3</SP>, OR<SP>3</SP> or halogen (where R<SP>3</SP> is C 1-6  alkyl, benzyl or phenethyl) with an acid hydrazide K<SP>1</SP>-CO-NH.NH 2 . Compounds I (R<SP>1</SP>=C 1-4  alkyl substituted by NH 2 , C 1-4  alkylamino or OH) are prepared by reacting a corresponding compound in which the alkyl group is substituted by or -O-CH(P)Q (where P and Q are phenyl (optionally substituted by X) or naphthyl (optionally substituted by X) and in addition one may be H and R<SP>11</SP> is H or C 1-4  alkyl) to replace the COCH(P)Q or CH(P)Q group with hydrogen. Compounds I (R<SP>2</SP> = R<SP>5</SP>COO or C 1-4  alkoxy) are prepared by reacting compound I (R<SP>2</SP>=Hal) with an acid R<SP>5</SP>COOH or an alkali metal or tri C 1-4  alkyl amine salt thereof or with a C 1-4  alkanol or alkali metal salt thereof. Compounds I (R<SP>2</SP>=OH( are prepared by hydrolysis of a compound I (R<SP>2</SP>=R<SP>5</SP>COO). Compounds I (R<SP>2</SP> = Hal) are prepared by reacting a compound I (R<SP>2</SP>=H) with a C 1-4  alkyl-C 3-5  cycloalkyl- or arylsulphonyl-N-haloamide in the presence of a free radical catalyst. Compounds I (R<SP>2</SP> = amino C 1-4  alkyl) are prepared by reacting a compound I (R<SP>2</SP> = H) with a base followed by an amino C 1-4  alkylating agent. Compounds I (m=0) are also prepared by reacting a compound 10 with an appropriate aryl halide in the presence of a Cu catalyst. In compounds I an X substituent MeS is oxidized to MeSO; an X substituent NO 2  is reduced to NH 2  which is acetylated. Compounds 2 are prepared by reacting a compound 17 with a compound [where S is halogen or C 1-4  alkyl or OH (when R<SP>2</SP> is C 1-4  alkyl)]. Compounds 2 (R<SP>2</SP>=H or C 1-4  alkyl) are prepared by cyclizing a compound 13 where R<SP>8</SP> is C 1-6  alkyl or phenyl optionally substituted by alkyl, aryl or aralkyl and R<SP>9</SP> is H or C 1-4  alkyl which may be prepared in situ by reduction of the corresponding nitro compound. Compounds 3 are prepared from compounds 2 by reaction with P 2 S 5 . Compounds 4 (Z = SR<SP>3</SP>) are prepared by alkylating a compound 3, compounds 4 (Z = Hal) by halogenating a compound 2 and compounds 4 (Z = OR<SP>3</SP>) by alkylating a compound 2. Compounds 10 are prepared by debenzylation of compounds I. Compounds 14 are prepared by reacting a compound 15 with a compound B-CO-CHR<SP>9</SP>-COOR<SP>8</SP> (where B is halogen or -OCOOR<SP>13</SP>. Compounds 17 are prepared by reducing compounds 15. Compounds 15 are prepared by reacting a (Y n -substituted)-phenylamine or -benzylamine with an (X n -substituted)-o-nitro phenylhalide. Compound II (X n =Z-NO 2 ) is reduced to the corresponding Z-NH 2  compound which is converted to Z-MeS compound via a diazonium sulphate derivative. Compounds I are CNS depressants and form with a carrier or diluent a pharmaceutical composition which may be administered orally or parenterally. They also increase growth rate and feed efficiency.