Patent GB-1139940-A (GB)
Title: Oxazole derivatives
Inventor: O'MANT DERRICK MICHAEL
IPC: A61K31/00
Filed: 1966-09-30
Abstract: 1,139,940. Oxazole derivatives. IMPERIAL CHEMICAL INDUSTRIES Ltd. 29 Aug., 1967 [30 Sept., 1966], No. 43786/66. Heading C2C. [Also in Division A5] Novel oxazole derivatives of general Formula (I) wherein Y is a phenyl or benzyl radical, either of which may be substituted in the ring by one or two halogen atoms or by a -CF 3  radical and Z is a -CR<SP>1</SP>(R<SP>2</SP>)(R<SP>3</SP>) radical wherein R<SP>1</SP> is H or C 1-3  alkyl, R<SP>2</SP> is H, C 1-3  alkyl or C 1-6  alkoxycarbonyl, and R<SP>3</SP> is a group -COOR<SP>4</SP> or -CONHR<SP>5</SP> wherein R<SP>4</SP> is H, alkyl, dialkylaminoalkyl, benzyl or phenyl and R<SP>5</SP> is H, -OH, -NH 2 , dialkylaminoalkyl, alkoxycarbonylalkyl or carboxyalkyl and their salts, are prepared: (a) when R<SP>3</SP> is -COOR<SP>4</SP> and R<SP>1</SP> and R<SP>2</SP> are H or alkyl, and R<SP>4</SP> is alkyl, benzyl or phenyl by reacting the appropriate nitrile or amide with R<SP>4</SP>OH under acidic conditions or if R<SP>4</SP> is H by hydrolysis of the corresponding esters; (b) when R<SP>1</SP> and R<SP>2</SP> are H or alkyl and R<SP>3</SP> is -CONH 2  by hydrolysis of the appropriate nitrile; (c) when R<SP>3</SP> is -COOR<SP>4</SP> and R<SP>4</SP> is not H by reacting Y.CO.NH 2  with X.CH 2 .CO.CR<SP>1</SP>R<SP>2</SP>.COOR<SP>4</SP> where X is a halo atom; (d) when R<SP>1</SP> is alkyl and R<SP>3</SP> is -COOR<SP>4</SP> by alkylating the corresponding compound in which R<SP>1</SP> is H; (e) where R<SP>1</SP> and R<SP>2</SP> are H or alkyl and R<SP>3</SP> is -COOH by hydrolysis of the corresponding nitrile or carbamoyl derivative; (f) when R<SP>1</SP> and R<SP>2</SP> are H or alkyl and R<SP>3</SP> is -CONHR<SP>5</SP> wherein R<SP>5</SP> is H, -OH, -NH 2  or dialkylaminoalkyl by reacting an appropriate ester with R<SP>5</SP>NH 2 ; (g) when R<SP>1</SP> and R<SP>2</SP> are H or alkyl and R<SP>3</SP> is -COOR<SP>4</SP> wherein R<SP>4</SP> is alkyl, dialkylaminoalkyl or benzyl by reacting a suitable salt wherein R<SP>3</SP> is -COO# with R<SP>4</SP>X where X is a halo atom; (h) when R<SP>1</SP> and R<SP>2</SP> are H or alkyl and R<SP>4</SP> is not H by reacting the appropriate compound where R<SP>4</SP> is H with R<SP>4</SP>OH; (i) when R<SP>3</SP> is -CONHR<SP>5</SP> wherein R<SP>5</SP> is dialkylaminoalkyl or alkoxycarbonylalkyl by reacting the appropriate carboxylic acid with R<SP>5</SP>NH 2 ; (j) when R<SP>1</SP> and R<SP>2</SP> are H or alkyl and R<SP>3</SP> is -CONHR<SP>5</SP> wherein R<SP>5</SP> is carboxyalkyl by hydrolysis of the corresponding ester wherein R<SP>5</SP> is alkoxycarbonylalkyl; (k) where R<SP>2</SP> is alkoxycarbonyl and R<SP>3</SP> is -COOR<SP>4</SP> wherein R<SP>4</SP> is alkyl by reacting sodium or potassium or a hydride, amide or alkoxide thereof with CO(OR<SP>4</SP>) 2  and the compound I wherein R<SP>2</SP> and R<SP>3</SP> are H; or (1) when R<SP>2</SP> is H and R<SP>3</SP> is -COOH by reacting a compound I where R 2  and R 3  are -COOR<SP>4</SP> where R<SP>4</SP> is alkyl with an inorganic base in water. Intermediates isolated are compounds of Formula (I) where Z is 4-chlorocarbonyl from the appropriate carboxylic acid and thionyl chloride; compounds of Formula (I) where Z is 4-hydroxymethyl by reduction of the said 4-chlorocarbonyl derivatives with sodium borohydride; compounds of Formula (I) where Z is 4-bromomethyl by reaction of the 4-hydroxy methyl derivatives with PBr 5 ; compounds of Formula (I) where Z is 4-cyanomethyl by reaction of the said bromomethyl derivatives with sodium cyanide; and 4-(4-bromophenyl)- 2-methyloxazole from acetamide and 4-bromophenacyl bromide.