Process for the preparation of 2-(primary/secondary amino)hydrocarbyl)-carbamoyl-7-oxo-2,6-diaza-bicyclo [3.2.0.]heptane-6-sulfonic acid derivatives

A process for the production of a compound of formula (I)

• wherein
• ALINKERB represents a linker moiety of formula
• A[G1-G2*-G3]B (V)
• wherein
• A and B indicate the orientation of the group of formula (V) in formula (I);
• G1, G2 or G3 may be present or absent, with the proviso that at least one of G1 or G3 is present;
• and,
• G1 if x is 1 and y is 1 and both, G2 and G3, are absent or if x is 1 and G2 and/or G3 are present, represents a C6-C14arylene;
• a saturated or non-aromatic unsaturated C3-C9cycloalkylene or a saturated or unsaturated heterocyclodiyl group comprising 5 to 9 ring atoms containing one or more heteroatoms selected from N, O and S, which groups may be unsubstituted or substituted or, if x is 0 and y is 1 and both, G2 and G3, are absent or if x is 0 and G2 and/or G3 are present, together with the group
• forms a heterocyclyl group comprising 5 to 9 ring atoms containing one or more heteroatoms selected from N, O and S, which may be unsubstituted or substituted;
• or,
• if x is 0 and y is 0 and both, G2 and G3, are absent, together with the groups
• forms a heterocyclyl group comprising 5 to 9 ring atoms containing two or more heteroatoms selected from N, O and S, which may be unsubstituted or substituted;
• G2 represents a group selected from
• —(CnH2n—)—;
• —(NH)—;
• —(C═O)—;
• —(C═O)NH—*;
• —HN(C═O)—*;
• —HN(C═O)NH—;
• —(CnH2n)—[X—CnH2n]m—(C═O)NH—*;
• —HN(C═O)—[CnH2n]—X]m—(CnH2n)—*;
• —(CnH2n)—[X—CnH2n]m—HN(C═O)—*;
• —(O═C)NH—[CnH2n]—X]m—(CnH2n)—*;
• —(CnH2n)—[X—CnH2n]m—HN(C═O)NH—*, and
• —HN(C═O)NH—(CnH2n)—[X—CnH2n]m—*
• wherein
• * indicates the bond of G2 indicated in formula (V) with * and X represents, independently at each occurrence,
• —O—;
• —NH—;
• —(C═O)NH—;
• —NH(C═O)—;
• —(C═O)O—;
• —O(C═O)—;
• —NH(C═O)NH—;
• —NH(C═O)O— or —O(C═O)NH—
• n is, independently at each occurrence, 1, 2, 3 or 4, in particular 2;
• and
• m is 0, 1, 2 or 3, in particular 0 or 1;
• and,
• G3 if y is 1 and G1 and/or G2 are present, represents a C6-C14arylene;
• a saturated or non-aromatic unsaturated C3-C9cycloalkylene or a saturated or unsaturated heterocyclodiyl group comprising 5 to 9 ring atoms containing one or more heteroatoms selected from N, O and S, which groups may be unsubstituted or substituted, or,
• if y is 0 and x is 1 and both, G1 and G2, are absent or if y is 0 and G1 and/or G2 are present, together with the group
• forms a heterocyclyl group comprising 5 to 9 ring atoms containing one or more heteroatoms selected from N, O and S, which may be unsubstituted or substituted,
• which linker group may furthermore optionally contain one or more groups of formula:
• and/or other substituents;
• R1 represents hydrogen or a C1-C4-alkyl group;
• R2 represents hydrogen or a C1-C4-alkyl group;
• R3 independently at each occurrence, represents hydrogen or a C1-C4-alkyl group;
• x is 0 or 1;
• y is 0 or 1;
• z independently at each occurrence, is 0 or 1;
• and
• (—) represents a single bond between a primary, secondary or tertiary carbon atom of the moiety ALINKERB and the adjacent nitrogen atom,
• in which process
• (A) a compound of formula (II)
• is reacted with a compound of formula (III)
• wherein
• Pr represents an amino protecting group selected from t-butyloxy carbonyl (t-Boc), 1-methyl-1-(4-biphenyl)ethyloxy carbonyl (Bpoc), 1-(1-adamantyl)-1-methylethyloxy carbonyl (Adpoc), 1-(3,5-di-t-butylphenyl)-1-methylethyloxy carbonyl (t-Bumeoc), 1-adamantyloxy carbonyl (Adoc), p-methoxybenzyloxy carbonyl (Moz) and o,p-dimethoxybenzyloxy carbonyl;
• ALINKERB has the same meaning as in formula (I) with the exception that one or more of the optional groups of formula:
• may be replaced by a group of formula:
• and
• R1;
• R2;
• R3;
• x;
• y;
• z and (—), at each occurrence, have the same meaning as in formula (I) and Pr is as defined above;
• in a dipolar aprotic solvent in the presence of a base to obtain a compound of formula (IV)
• wherein
• Pr;
• ALINKERB;
• R1;
• R2;
• R3;
• x;
• y;
• z;
• and (—), at each occurrence, have the same meaning as in formula (III);
• which compound is then
• (B) deprotected by reaction with formic acid or a mixture of formic acid or acetic acid with hydrochloric acid or hydrobromic acid, to give the compound of formula (I).