Patent GB-1266544-A (GB)
IPC: C07D499/12
Filed: 1969-05-06
Abstract: 1,266,544. Organosilane penicillins. AMERICAN HOME PRODUCTS CORP. 6 May, 1969 [8 May, 1968], No. 23040/69. Headings C3S and C3T. [Also in Division C2] Novel 6-aminopenicillanic acid derivatives of the formula wherein R<SP>1</SP> is hydrogen, alkyl, aryl or aralkyl, R<SP>2</SP> is halogen, alkyl, aryl or aralkyl, R<SP>a</SP> is hydrogen, W is hydrogen or a group of the formula X is halogen, m is 0 or 1, n is an integer of from 1 to 25, p is 0 or 1, and Y is halogen or a group of the formula with the provisos that: (a) when m is 0 and p is 0, n is more than 1 and the two free valencies are joined together to complete a cyclic compound, (b) when n is more than 1, the moieties A of the additional groups B recur in random headtoward-head head-toward-tail and tail-towardtail disposition, (c) m is always equal to p, and (d) when R<SP>1</SP> is alkyl, aryl or aralkyl, R<SP>2</SP> is halogen, are prepared by reacting 6-aminopenicillanic acid or a salt thereof with a di- or tri-halosilane of the formula preferably in an anhydrous non-hydroxylic organic solvent and in the presence of an acid acceptor. The above novel organosilane penicillins and further analogous compounds in which proviso (d) above does not apply may be reacted with a reactive derivative of an organic carboxylic acid R<SP>b</SP>COOH to provide novel and other compounds corresponding to the first general formula, in which the symbol R<SP>a</SP> represents an acyl residue R<SP>b</SP>CO- of the organic carboxylic acid used. These latter compounds may be subsequently subjected to hydrolysis or alcoholysis to provide corresponding penicillin acids, which in turn may be converted to appropriate salts thereof. In examples the acyl group R<SP>b</SP>CO- is derived from D(-) phenylglycyl chloride, hydrochloride, 1-amino-1-cyclohexanecarboxylic acid chloride hydrochloride, 2-amino- 2-carboxyindane acid chloride hydrochloride, 1- aminocyclopentane-carboxylic acid chloride hydrochloride, 2 - amino - 1,2,3,4 - tetrahydro- 6-methoxy-2-naphthoic acid chloride hydrochloride, 2-amino-1,2,3,4-tetrahydro-7-ethoxy- 2-naphthoic acid chloride hydrochloride, 2- amino-4-phenyl-2-indan-carboxylic acid chloride hydrochloride, 2-amino-3-phenoxy-2-indancarboxylic acid chloride hydrochloride, 2-amino- 4-butyl-2-indan-carboxylic acid chloride hydrochloride, 1-amino-7-methyl-1-indan-carboxylic acid chloride hydrochloride, phenoxyacetyl chloride, and 3-(2,6-dichlorophenyl)-5-methylisoxazole-4-carbonyl chloride. Subsequent hydrolysis provided the following compounds:- ampicillin, ampicillin beta-naphthalene sulphonate, 6-(1-aminocyclo-hexanecarboxamido) penicillanic acid, 6-(2-amino-2-indancarboxamido) penicillanic acid, 6-(1-aminocyclopentanecarboxamido) penicillanic acid, 6-(2-amino-1,2,3,4- tetrahydro-6-methoxy-2-naphthamido) penicillanic acid, 6-(2-amino-1,2,3,4-tetrahydro-7-ethoxy-2-naphthamido) penicillanic acid, 6-(indan- 2-amino-4-phenyl-2-carboxamido) penicillanic acid, 6-(indan-2-amino-3-phenoxy-2-carboxamido) penicillanic acid, 6-(indan-2-amino-4-butyl- 2-carboxamido) penicillanic acid, 6-(indan-1- amino - 7 - methyl - 1 - carboxamido) penicillanic acid, penicillin V, and dicloxacillin acid. Uses:-As antibiotics.