US4385178A — Process for producing 7-(substituted)amino-3-subs…

Claim 1

Independent Claim 239 words

A process for producing a 7-(substituted)-amino-3-substituted thiomethyl cephem carboxylic acid represented by the formula: ##STR17## wherein R 1 is a hydrogen atom; R 2 is an amino group; and R 8 is a moiety of a compound of the formula HSR 8 wherein SR 8 is a conventional 3-position cephalosporin thio substituent wherein R 8 is an unsubstituted or substituted ring carbon containing heterocyclic group, or said compound (I) in which the carboxyl group is protected by a conventional cephalosporin carboxy protecting group or a conventional cephalosporin salt thereof, which comprises reacting a cephalosporanic acid represented by the formula: ##STR18## wherein R 1 and R 2 have the same meanings as defined above; X is carboxylic acyloxy or carbamoyloxy group or one of said groups substituted by a conventional cephalosporin substituent; >Y is >S or>S→O; or said compound (II) in which the carboxyl group is protected by a conventional cephalosporin carboxy protective group or a conventional cephalosporin salt thereof, with a thiol compound represented by the formula: R.sup.8 --SH (III) wherein R 8 has the same meaning as defined above, or a salt thereof with a compound forming a conventional cephalosporin salt, in a non-aqueous organic solvent at a temperature of -20° to 80° C. in the presence of boron trifluoride or a complex compound thereof which acts as boron trifluoride, the boron and the fluorine bonded to boron in said complex compound being present as BF 3 .

Claim 2

Dependent Claim 239 words

A process for producing a 7-(substituted)-amino-3-substituted thiomethyl cephem carboxylic acid represented by the formula: ##STR17## wherein R 1 is a hydrogen atom; R 2 is an amino group; and R 8 is a moiety of a compound of the formula HSR 8 wherein SR 8 is a conventional 3-position cephalosporin thio substituent wherein R 8 is an unsubstituted or substituted ring carbon containing heterocyclic group, or said compound (I) in which the carboxyl group is protected by a conventional cephalosporin carboxy protecting group or a conventional cephalosporin salt thereof, which comprises reacting a cephalosporanic acid represented by the formula: ##STR18## wherein R 1 and R 2 have the same meanings as defined above; X is carboxylic acyloxy or carbamoyloxy group or one of said groups substituted by a conventional cephalosporin substituent; >Y is >S or>S→O; or said compound (II) in which the carboxyl group is protected by a conventional cephalosporin carboxy protective group or a conventional cephalosporin salt thereof, with a thiol compound represented by the formula: R.sup.8 --SH (III) wherein R 8 has the same meaning as defined above, or a salt thereof with a compound forming a conventional cephalosporin salt, in a non-aqueous organic solvent at a temperature of -20° to 80° C. in the presence of boron trifluoride or a complex compound thereof which acts as boron trifluoride, the boron and the fluorine bonded to boron in said complex compound being present as BF 3 .

Claim 3

Dependent Claim 50 words

The process according to claim 1 wherein R 8 is 5-(1,2,3,4-tetrazolyl), 5-(1-methyl-1,2,3,4-tetrazolyl), 5-(1-ethyl-1,2,3,4-tetrazolyl), 5-(1-sulfomethyl-1,2,3,4-tetrazolyl), 5-(1-carboxymethyl- 1,2,3,4-tetrazolyl), 5-[2-(2-carbamoylethyl)-1,2,3,4-tetrazolyl], 5-[1-(2-sulfamoylethyl)-1,2,3,4-tetrazolyl], 5-[1-(2-N,N-dimethylaminoethyl)-1,2,3,4-tetrazolyl], 5-[2-(2-N,N-dimethylaminoethyl)-1,2,3,4-tetrazolyl], 5-[1-(2-N,N-diethylaminoethyl)-1,2,3,4-tetrazolyl], 5-(1-methoxycarbonylmethyl-1,2,3,4-tetrazolyl), 5-(1-carbamoylmethyl-1,2,3,4-tetrazolyl), 5-[1-(2-hydroxyethyl)-1,2,3,4-tetrazolyl], 5-[1-(2-aminoethyl)-1,2,3,4-tetrazolyl], 5-(1-phenyl-1,2,3,4-tetrazolyl), 5-(1-vinyl-1,2,3,4-tetrazolyl), 2-(1,3,4-thiadiazolyl), 2-(5-methyl-1,3,4-thiadiazolyl), 2-(5-ethyl-1,3,4-thiadiazolyl), 2-(5-amino-1,3,4-thiadiazolyl), 2-(5-phenyl-1,3,4-thiadiazolyl), 5-(3-methyl-1,2,4-thiadiazolyl), 2-(5-carboxymethyl-1,3,4-thiadiazolyl), 5-(1,2,3-triazolyl), 2-(1-methyl-1,3,4-triazolyl), 2-(5-methyl-1,3,4-triazolyl), 2-(1,5-dimethyl-1,3,4-triazolyl), 4-(5-ethoxycarbonyl-1,2,3-triazolyl), 4-(5-carboxy-1,2,3-triazolyl), 2-(5-ethoxycarbonylmethyl-1,3,4-triazolyl), benzoxazolyl, 2-(benzimidazolyl), 2-(5-methyl-1,3,4-oxadiazolyl), 2-(5-methyl-1,3-thiazolyl), 2-(5-methyl-1,3-oxazolyl), 2-(1,3-thiazolyl), 5-(1,2,3,4-thiatriazolyl) or 2-(imidazolyl).

Claim 4

Dependent Claim 22 words

The process according to claim 1, wherein R 8 is 2-(1,3,4-thiadiazolyl), 2-(5-methyl-1,3,4-thiadiazolyl), 2-(1-methyl-1,3,4-triazolyl), 5-(1,2,3,4-tetrazolyl), 5-(1-methyl-1,2,3,4-tetrazolyl), 5-(1-carbamoylmethyl-1,2,3,4-tetrazolyl), 5-[1-(2-hydroxyethyl)-1,2,3,4-tetrazolyl], 5-(1vinyl-1,2,3,4-tetrazolyl), 5-[1-(2-aminoethyl)-1,2,3,4-tetrazolyl], 5-[2-(2-N,N-dimethylaminoethyl)-1,2,3,4-tetrazolyl] or 5-[1-(2-N,N-dimethylaminoethyl)-1,2,3,4-tetrazolyl].

Claim 5

Dependent Claim 24 words

The process according to claim 3, wherein the objective compound is a compound represented by the general formula (I) set forth in claim 1.

Claim 6

Dependent Claim 34 words

The process according to claim 4, wherein a compound represented by the general formula (II) set forth in claim 1 wherein >Y is >S and X is acetoxy is used as the starting compound.

Claim 7

Dependent Claim 11 words

The process according to claim 5, wherein R 8 is 5-(1-methyl-1,2,3,4-tetrazolyl).

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1986-05-23	1986-11-22	1987-05-24	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1990-05-23	1990-11-22	1991-05-24	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	1994-05-23	1994-11-22	1995-05-24	$7700.00	Window Closed / Lapsed

Process for producing 7-(substituted)amino-3-substituted thiomethyl cephem carboxylic acids

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