Beta-lactam antibiotics

Claim 2

A β-lactam having sulfonic acid salt substituent -SO 3 ⊖ M ⊕ wherein M is hydrogen or a cation in the 1-position and having one or two alkyl, cycloalkyl, phenyl or substituted phenyl substituents in the 4-position or a single alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl or 2-phenylethynyl substituent in the 4-position and an amino substituent -NH 2 or a protected form thereof in the 3-position.

Claim 3

A β-lactam in accordance with claim 1 having a sulfonic acid salt substituent -SO 3 ⊖ M ⊕ wherein M⊕ is hydrogen or a cation in the 1- position, an amino substituent -NH 2 in the 3-position and an alkyl substituent in the 4-position.

Claim 4

A β-lactam in accordance with claim 2 having a sulfonic acid salt substituent -SO M ⊕ wherein M is hydrogen or a cation in the 1- position, an amino substituent -NH 2 in the 3-position and a methyl substituent in the 4-position.

Claim 5

A β-lactam in accordance with claim 1 having the formula wherein R 2 is hydrogen or alkoxy of 1 to 4 carbon atoms; R 3 and R 4 are the same or different and each is alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R 3 and R 4 is hydrogen and the other is alkyl, cycloalkyl, phenyl, substituted phenyl, alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl or 2-phenylethynyl; and M is hydrogen or a cation.

Claim 6

A β-lactam in accordance with claim 4 wherein R 2 is hydrogen.

Claim 7

A β-lactam in accordance with claim 5 wherein R3 and R4 are methyl.

Claim 8

A β-iactam in accordance with claim 5 wherein one of R3 and R 4 is hydrogen.

Claim 9

A β-lactam in accordance with claim 5 wherein R 3 is hydrogen and R 4 is methyl.

Claim 10

A β-lactam in accordance with claim 5 wherein R 3 is methyl and R 4 is hydrogen.

Claim 11

A β-iactam in accordance with claims 4 through 9 wherein the amino substituent (NH 2 -) in the 3-position is protected.

Claim 12

A β-lactam in accordance with claim 10 wherein the amino substituent is in the form of an azido group.

Claim 13

A β-lactam in accordance with claim 11 having the formula wherein one of R 3 and R 4 is hydrogen and the other is alkyl and M 0 is hydrogen or a cation.

Claim 14

A,β-lactam according to claim 12 wherein one of R 3 and R 4 is hydrogen and the other is methyl.

Claim 15

A β-lactam having a sulfonic acid salt substituent -SO M ⊕ wherein M is hydrogen or a cation in the 1-position and an acylamino substituent in the 3-position.

Claim 16

A β-lactam having a sulfonic acid salt substituent -SO M ⊕ wherein M is hydrogen or a cation in the 1-position and an acylamino substituent in the 3-position.

Claim 17

A β-lactam in accordance with claim 14 having a sulfonic acid salt substituent -SO M ⊕ wherein M ⊕ is hydrogen or a cation in the 1- position, an acylamino substituent in the 3- position and an alkyl substituent in the 4- position.

Claim 18

A β-lactam in accordance with claim 14 having a sulfonic acid salt substituent -SO M ⊕ wherein M is hydrogen or a cation in the 1- position, an acylamino substituent in the 3-position and a methyl substituent in the 4-position.

Claim 19

A β-lactam in accordance with claim 14 having the formula wherein R 1 is acyl; R 2 is hydrogen or alkoxy of 1 to 4 carbon atoms; R 3 and R 4 are the same or different and each is alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R 3 and R 4 is hydrogen and the other is alkyl, cycloalkyl, phenyl, substituted phenyl, alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl or 2-phenylethynyl; and M ⊕ is hydrogen or a cation.

Claim 20

A β-lactam in accordance with claim 17 wherein R 2 is hydrogen.

Claim 21

A β-lactam in accordance with claim 18 wherein R 3 and R 4 are methyl.

Claim 22

A β-iactam in accordance with claim 18 wherein one of R 3 and R 4 are hydrogen.

Claim 23

A β-lactam in accordance with claim 18 wherein R 3 is hydrogen and R 4 is methyl.

Claim 24

A β-iactant in accordance with claim 18 wherein R 3 is methyl and R 4 is hydrogen.

Claim 25

A β-lactam in accordance with claims 17 through 22 wherein R 1 is an aliphatic group having the formula wherein R 5 is alkyl; cycloalkyl; alkoxy; alkenyl; cycloalkenyl; cyclohexadienyl; or alkyl or alkenyl substituted with one or more halogen, cyano, nitro, amino, mercapto, alkylthio, or cyanomethylthio groups.

Claim 26

A β-lactam in accordance with claims 17 through 22 wherein R 1 is a carbocyclic aromatic group having the formula or wherein n is 0, 1, 2 or 3;R 6 , R 7 and.R 8 each is independently hydrogen, halogen, hydroxyl, nitro; amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbons atoms, alkoxy of 1 to 4 carbon atoms or aminomethyl; and R 9 is amino, hydroxyl, a carboxyl salt, protected carboxyl, formyloxy, a sulfo salt, a sulfoamino salt, azido, halogen, hydrozino, alkylhydrazino, phenylhydrazino, or [(alkylthio)thioxomethyl]thio.

Claim 27

A β-lactam in accordance with claims 17 through 22 wherein R 1 is a heteroaromatic group having the formula or wherein n is 0, 1, 2 or 3; R 9 is amino, hydroxyl, a carboxyl salt, protected carboxyl, formyloxy, a sulfo salt, a sulfoamino salt, azido, halogen, hydrazino, alkylhydrazino, phenylhydrazino or [(alkylthio)-thioxomethyl]thio; and R 10 is a substituted or unsubstituted 5-,6- or 7-membered heterocyclic aromatic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms.

Claim 28

A β-lactam in accordance with claims 17 through 22 wherein R 1 is a group having the formula wherein R 11 is (i) a group having the formula wherein R 6 , R 7 and R 8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of I to 4 carbon atoms, or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen,_oxygen and sulfur atoms; and R12 is -N=CH-R 11 ' alkylcarbonylamino, alkyl or alkyl substituted with one or more halogen, cyano, nitro, amino or mercapto groups.

Claim 29

A β-lactam in accordance with claims 17 through 22 wherein R 1 is a group having the formula wherein R 11 is (i) a group having the formula wherein R 6 , R 7 and R 8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy or 1 to 4 carbon atoms or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms and R 13 is hydrogen, alkyl, cycloalkyl, alkylaminocarbonyl, or alkyl substituted with one or more halogen, cyano, nitro, amino, mercapto, alkylthio, R 11 , carboxyl, carboxyl salt, amido, alkoxycarbonyl, phenylmethoxycarbonyl, diphenylmethoxycarbonyl, hydroxyalkoxyphosphinyl, dihydroxyphosphinyl, hydroxy(phenyl- methoxy)phosphinyl or dialkoxyphosphinyl substituents.

Claim 30

A β-lactam in accordance with claims 17 through 22 wherein R 1 is a group having the formula wherein R 11 is (i) a group having the formula wherein R 6 , R 7 and R 8 each is independently hydrogen, halogen, hydroxy, nitro, amino, cyano, trifluoromethyl, alkyl or 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R 14 is wherein n is 0, 1, 2 or 3, amino, alkylamino, (cyanoalkyl)amino, amido, alkylamido, (cyanoalkyl)-amido

Claim 31

A β-lactam in accordance with claims 17 through 22 wherein R 1 is a group having the formula wherein R 11 is (i) a group having the formula wherein R 6' R 7 and R 8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R 15 is hydrogen, alkylsulfonyl, -N=CH-R 11 , wherein R 16 is hydrogen, alkyl, or halogen substituted alkyl, R 11 , alkyl, or alkyl substituted with one or more halogen, cyano, nitro, amino or mercapto groups.

Claim 32

A β-lactam in accordance with claim 27 wherein R 11 is 2-amino-4-thiazolyl.

Claim 33

A β-lactam in accordance with claim 30 a salt of [3S-(3αZ),4β]]-3-[[(2-amino-4-thiazolyl)-(methoxyimino)acetyl]amino]-4-methyl-2-oxo-1- azetidinesulfonic acid.

Claim 34

32 . A β-lactam in accordance with claim 30 a salt of [3S-I3α(Z),4BI]-3-[[[(carboxymethoxy)-imino](2-amino-4-thiazolyl)acetyl]amino]-4-methyl-2-oxo-l-azetidinesulfonic acid.

Claim 35

A β-lactam in accordance with claim 3 0 a salt of [3S-[3α(Z),4B]]-3-[I(2-amino-4-thiazolyl)-[(1-carboxy-1-methylethoxy)imino]acetyl]amino]-4-methyl-2-oxo-I-azetidinesulfonic acid.

Claim 36

A β-lactam in accordance with claim 30 [3S-[3α(Z),4β]]-3-(I(2-amino-4-thiazolyl) [(1-carboxyl-methylethoxy)imino]acetyl]amino]-4-methyl-2-oxo-l-azetidinesulfonic acid, dipotassium salt.

Claim 37

A β-lactam in accordance with claim 30 a salt of [3S-[3α(Z),4a]-3-[[2-amino-4-thiazolyl)-methoxyimino)acetyl]amino]-4-methyl-2-oxo-I-azetidinesulfonic acid.

Claim 38

A β-lactam in accordance with claim 30 a salt of [3S-[3α(Z),4α]]-3-j[(2-amino-4-thiazolyl)-[(1-carboxy-l-methylethoxy)imino]acetyl]amino]-4-methyl-2-oxo-l-azetidinesulfonic acid.

Claim 39

A β-lactam in accordance with claim 29 wherein R 1 is a group having the formula

Claim 40

A β-lactam in accordance with claim 37 wherein R 1 is a group having the formula

Claim 41

A β-lactam in accordance with claim 37 a salt of [3S-[3α(R*),4β]]-3-[[[[[3-[(2-furanylmethylene)amino]-2-oxo-1-imidazolidinyl]carbonyl]-amino]phenylacetyl]amino]-4-methyl-2-oxo - l-azetidinesulfonic acid.

Claim 42

A β-lactam in accordance with claim 37 a salt of [3S-[3a(R*) ,4α]]-3-[[[[3-[(2-furanylmethylene)amino]-2-oxo-l-imidazolidinyl]carbonylamino]phenylacetyl]amino]-4-methyl-2-oxo-l-azetidinesulfonic acid.

Claim 43

A β-lactam in accordance with claim 26 wherein R 1 is a group having the formula

Claim 46

A β-lactam in accordance with claim 41 a salt of [3S-[3α(R*),4β]]-3-[[[[(4-ethyl-2,3-dioxo-l-piperazinyl)carbonyl]amino]phenylacetyl]-amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.

Claim 47

A β-lactaia in accordance with claim 41 a salt of [3S-[3a(R*),4a]]-3-[[[[(4-ethyl-2,3-dioxo-l-piperazinyl)carbonyl]amino]phenylacetyl]-amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.

Claim 48

A.compound according to claims 1 to 3 wherein the amino group is in the protected form of an azide (- N 3 ).

Claim 49

A β-lactam in accordance with claim 44 having a sulfonic acid salt substituent -SO 3 ⊖ M ⊕ wherein M ⊕ is hydrogen or a cation in the 1-position, an azido substituent -N 3 in the 3-position and an alkyl substituent in the 4-position.

Claim 50

A β-lactam in accordance with claim 44 having a sulfonic acid salt substituent -SO 3 ⊖ M ⊕ wherein M is hydrogen or a cation in the 1-position, an azido substituent -N 3 in the 3-position and a cycloalkyl, phenyl or substituted phenyl substituent in the 4-position.

Claim 51

A β-lactam in accordance with claim 44 having a sulfonic acid salt substituent -SO 3 ⊖ M ⊕ wherein M is hydrogen or a cation in the 1-position, an azido substituent -N 3 in the 3-position and an alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl or 2-phenylethynyl substituent in the 4-position.

Claim 52

A β-lactam in accordance with claim 45 having the formula wherein R 2 is hydrogen or alkoxy of 1 to 4 carbon atoms; R 3 and R 4 are the same or different and each is alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R 3 and R 4 is hydrogen and the other is alkyl, cycloalkyl, phenyl, substituted phenyl, alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl or 2-phenylethynyl; and M ⊕ is hydrogen or a cation.

Claim 53

A compound of the formula wherein R 1 , R 3 , R 4 and M are as defined in claim 4, and V is a leaving group such as methanesulfonyl, benzenesulfonyl, toluenesulfonyl, chloro, bromo or iodo.

Claim 54

A compound of the formula wherein R 2 , R 3 and R 4 are as defined in claim 4.

Claim 55

A compound of the formula wherein R 1 , R 3 , R 4 and M are as defined in claim 4.

Claim 56

A process for preparing a compound of the formula wherein A is a protecting group and V, R 3 and R 4 and M are as defined in claim 49 which comprises sulfonating a compound of the formula wherein the symbols are as defined above.

Claim 57

A compound of the formula wherein the symbols are as defined in claim 52.

Claim 58

A compound of the formula wherein R 2 , R 3 , R 4 and M are as defined in claim 4.

Claim 59

A β-lactam in accordance with claim 1 as named in any of the Examples.

Claim 60

A process for preparing a β-lactam having a sulfonic acid salt substituent -SO 3 - M + wherein M + is hydrogen or a cation, in the 1- position and an amino substituent -NH 2 or a protected form thereof in the 3-position and having one or two alkyl, cycloalkyl, phenyl or substituted phenyl substituents in the 4-position or a single alkoxy- ; carbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl or 2-phenylethynyl substituent in the 4-position by sulfonating a corresponding β-lactam having a hydrogen substituent in the 1- position and a protected amino substituent in the 3-position and removing said amino protecting group.

Claim 61

A process for preparing a β-lactam having a sulfonic acid salt substituent -SO 3 - M + wherein M + is hydrogen or a cation, in the 1- position and an amino substituent -NH 2 or a protected form thereof in the 3-position and having one or two alkyl, cycloalkyl, phenyl or substituted phenyl substituents in the 4-position or a single alkoxy- ; carbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl or 2-phenylethynyl substituent in the 4-position by sulfonating a corresponding β-lactam having a hydrogen substituent in the 1- position and a protected amino substituent in the 3-position and removing said amino protecting group.

Claim 62

A process according to claim 56 wherein the amino substituent in the 3-position is acylated, said acyl group containing a basic function when M is hydrogen and said acylation is effected either before or after the sulfonation reaction.

Claim 63

A process according to claims 5 6 and 57 wherein the product contains an alkyl substituent in the 4- position.

Claim 64

A process according to claims 56 through 58 wherein the product is of the formula wherein R 1 is hydrogen or acyl or the group R 1 -NH- is protected amino; R 2 is hydrogen or C l -C 4 alkoxy; R 3 and R 4 are the same or different and each is alkyl, cycloalkyl, phenyl or substituted phenyl, or one or R 3 and R 4 is hydrogen and the other is alkyl, cycloalkyl, phenyl, substituted phenyl, alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl or 2-phenylethynyl; and M is hydrogen or a cation and said sulfonation is effected on a compound of the formula or a precursor compound of the formula which is cyclized, said sulfonation reaction being effected either before or after said cyclization, R 1 -NH- in the reactants being a protected amino group or R 1 being acyl; V being a leaving group such as methanesulfonyl, benzenesulfonyl, toluenesulfonyl, chloro, bromo or iodo; and R 2 , R 3 and R. being as previously defined.

Claim 65

A process according to claim 59 wherein R 1 is hydrogen or the group R 1 -NH- is a protected amino group.

Claim 66

A process according to claim 59wherein R 1 is acyl.

Claim 67

A process according to claim 61 wherein the acyl group is selected from the group consisting of (a) an aliphatic group having the formula wherein R 5 is alkyl; cycloalkyl; alkoxy, alkenyl; cycloalkenyl, cyclohexadienyl; or alkyl or alkenyl substituted with one or more halogen, cyano, nitro, amino, mercapto, alkylthio, or cyanomethylthio groups; (b) a carbocyclic aromatic group having the formula or wherein n is 0, 1, 2 or 3; R 6 , R 7 and R 8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or aminomethyl; and R 9 is amino, hydroxyl, a carboxyl salt, protected carboxyl, formyloxy, a sulfo salt, a sulfoamino salt, azido, halogen, hydrazino, alkylhydrazino, phenylhydrazino, or [(alkylthio)thioxomethyl]thio; (c) a heteroaromatic group having the formula or wherein n is 0, 1 2 or 3; R 9 is amino, hydroxyl, a carboxyl salt, protected carboxyl, formyloxy, a sulfo salt, a sulfoamino salt, azido, halogen, hydrazino, alkylhydrazino, phenylhydrazino or [(alkylthio)thioxomethyl]thio; and R 10 is a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic aromatic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; (d) a group having the formula wherein R 11 is (i) a group having the formula wherein R 6 , R 7 and R 8 each is independently hydrogen, halogen, hydroxy, nitro, amino, cyano, trifluoromethyl, alkyl or 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R 12 is -N=CH-R 11 , -NH-C-R 11 , alkylcarbonylamino, alkyl or alkyl substituted with one or more halogen, cyano, nitro, amino or mercapto groups; (e) a group having the formula wherein R 11 is (i) a group having the formula wherein R 6 , R 7 and R 8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R 13 is hydrogen, alkyl, cycloalkyl, alkylaminocarbonyl, -C-NH-R 11 , or alkyl substituted with one or more halogen, cyano, nitro, amino, mercapto, alkylthio, R 11 , carboxyl, carboxyl salt, amido, alkoxycarbonyl, phenylmethoxycarbonyl, diphenylmethoxycarbonyl, hydroxyalkoxyphosphinyl, dihydroxyphosphinyl, hydroxy(phenylmethoxy)phosphinyl or dialkoxyphosphinyl substituents; (f) a group having the formula wherein R 11 is (i) a group having the formula wherein R 6 , R 7 and R 8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R 14 is wherein n is 0, 1,2 or 3, amino, alkylamino, (cyanoalkyl)amino, amido, alkylamido, (cyanoalkyl)amido, (g) a group having the formula wherein the R 11 is (i)R 7 a group having the formula wherein R 6 , R 7 and R 8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R 15 is hydrogen, alkylsulfonyl, -N=CH-R 11 wherein R 16 is hydrogen, alkyl, or halogen substituted alkyl, R 11 ,alkyl, or alkyl substituted with one or more halogen, cyano, nitro, amino or mercapto groups.

Claim 68

A process in accordance with claim 62 wherein R 11 is 2-amino-4-thiazolyl.

Claim 69

64 . A process in accordance with claim 63 wherein the product is a salt of [3S-[3α(Z),4β]]-3-[[(2-amino-4-thiazolyl)-methoxyimino)acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.

Claim 70

A process in accordance with claim 63 wherein the product is a salt of [3S-[ 3a(Z), 4β[[-3-[[[carboxy- methoxy)-imino](2-amino-4-thiazolyl)acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.

Claim 71

A process in accordance with claim 63 wherein the product is a salt of [3S- [3α(Z) , 4β]]-3-[[(2-amino-4-thiazolyl)-[(l-carboxy-l-methylethoxy)imino]acetyl]-amino]-4-methyl-2-oxo-l-azetidinesulfonic acid.

Claim 72

A process in accordance with claim 66 wherein the product is [3S-[3α(Z),4β]]-3-[[(2-amino-4-thiazolyl)-[(1-carboxy-l-methylethoxy)imino]acetyl]amino]-4-methyl-2-oxo-l-azetidinesulfonic acid, dipotassium salt.

Claim 73

A process in accordance with claim 63 wherein the product is a salt of [3S- [3a(Z),4a]]-3-[[2-amino-4-thiazolyl)-methoxyimino)acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.

Claim 74

A process in accordance with claim 63 wherein the product is a salt of [3S-[3a(Z),4a]]-3-[[(2-amino-4-thiazolyl)-[(1-carboxy-l-methylethoxy)imino]acetyl]-amino]-4-methyl-2-oxo-l-azetidinesulfonic acid.

Claim 75

A process in accordance with claim 62 wherein the product is a salt of [3S-[3α(R*)4β]]-3-[[[[[3-[(2-furanylmethylene)amino]-2-oxo-1-imidazolidinyl]carbonyl]-amino]phenylacetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.

Claim 76

A process in accordance with claim 62 wherein the product is a salt of [3S-[3α(R*),4α]]-3-[[[[[3-[(2-furanylmethylene)amino]-2-oxo-1-imidazolidinyl]carbonyl]-amino]-henylacetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.

Claim 77

A process in accordance with claim 62 wherein the product is a salt of [3S-[3a(R*),4β]]-3-[[[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]phenylacetyl]amino]-4-methyl-2-oxo-l-azetidinesulfonic acid.

Claim 78

A process in accordance with claim 62 wherein the product is a salt of [3S-[3a(R * ),4a]]-3-[[[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]phenylacetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid.

Claim 79

A process according to the preceding claims wherein the sulfonation is effected by treatment with a sulfur trioxide complex or an equivalent sulfonating reagent.

Claim 80

A process according to claim 74 wherein the sulfonating complex is pyridine sulfur trioxide complex.

Claim 81

A process according to claim 19 wherein the sulfonating complex is dimethylformamide-sulfur trioxide complex.

Claim 82

A process according to claim 1 wherein the amino substituent in the 3-position is in the protected form of an azide.

Claim 83

A process according to claim 4 wherein the group R 1 -NH is an amino group in the protected form of an azide.

Claim 84

A process according to claims 22 and 23 wherein the azide protecting group is reduced to form the amino substituent (-NH 2 ).

Claim 85

A process according to claims 56 and 59 wherein the amino protecting group is benzyloxycarbonyl or butyloxycarbonyl.

Claim 86

A process according to claims 56, 58 and 59 wherein the product is of the formula 'wherein the various groups are as defined in claim 59 and the amino group can be in a protected form.

Claim 87

A process according to claim 59 wherein R 2 is hydrogen and one of R 3 and R 4 is hydrogen and the other is alkyl.

Claim 88

A process according to claim 77 wherein the alkyl group is methyl.

Claim 89

.A process according to the preceding claims wherein the cation M + is a pyridinium ion or a tetrabutylammonium ion or a potassium ion.