Beta-lactamase inhibitors

1. A process for preparing a compound of Formula (A-I):

wherein

Z is selected from the group consisting of 1,3,4-oxadiazole, 1,2,4-oxadiazole, 1,3,4-thiadazole and 1,2,4-thiadazole;

R* is —OSO 3 H; and

R 1 * is selected from:

a. hydrogen;

b.

wherein

R 2 * is selected from

R 3 * is selected from hydrogen, (C 1 -C 3 )-alkyl, aminoalkyl, aminocycloalkyl, hydroxyalkyl,

each of R 4 *, R 5 *, R 6 *and R 7 * is independently selected from hydrogen or (C 1 -C 6 )-alkyl, aminoalkyl, aminocycloalkyl, and hydroxyalkyl, provided that at least one of R 4 *, R 5 *, R 6 *and R 7 * is hydrogen,

n is selected from 1, 2, 3 and 4, and

m is selected from 1, 2 and 3;

c.

wherein R 8 * is selected from NH 2 ,

wherein each of R 4 *, R 5 *, R 6 *and R 7 * is as described previously and each of R 9 , R 10 , and R 11 is independently selected from hydrogen or (C 1 -C 6 )-alkyl, provided that at least one of R 9 , R 10 , and R 11 is hydrogen;

d. amino;

e.

wherein Z* is selected from CR 12 R 13 or NR 14 ,

each of R 12 and R 13 is independently selected from H, NH 2 and

wherein each of R 4 *, R 5 *, R 6 *and R 7 * is as described previously, alternatively, R 12 and R 13 together with the carbon to which they are attached, form a cycloalkyl or heterocyclyl ring containing 4-6 ring members,

R 14 is selected from H and

wherein each of R 15 , R 16 , and R 17 is independently selected from hydrogen, (C 1 -C 6 )-alkyl, aminoalkyl, aminocycloalkyl, and hydroxyalkyl, provided that at least one of R 15 , R 16 and R 17 is hydrogen,

R 18 is selected from NH 2 and

wherein each of R 4 *, R 5 *,

R 6 *and R 7 * is as described previously,

each of p* and q* is independently selected from 0, 1, 2 and 3,

T is selected from NH and O

t is selected from 0, 1, 2, 3, and 4, and

each of r and y is independently selected from 0 and 1;

f.

wherein R 19 is selected from NH 2 and

wherein each of R 4 *,

R 5 *, R 6 *and R 7 * is as described previously,

R 20 is selected from amino and hydroxyl, and

w is selected from 0 and 1;

g.

h.

wherein each of R 4 *, R 5 *, R 6 *and R 7 * is as described previously;

i.

wherein R 21 is selected from NH 2 , —NH(C 1 -C 3 )-alkyl and

wherein each of R 4 *, R 5 *, R 6 *and R 7 * is as described previously,

s is selected from 0 and 1, and

v is selected from 0, 1, 2, and 3;

j.

k.

wherein M is selected from NR 22 , CR 23 R 24 and O,

wherein R 22 is H or

wherein each of R 15 , R 16 and R 17 is as described previously,

each of R 23 and R 24 is independently selected from H, NH 2 and

wherein each of R 4 *, R 5 *, R 6 * and R 7 * is as described previously, and

u is selected from 0, 1 and 2;

l.

m.

n.

o. (C 1 -C 3 )-unsubstituted alkyl; and

p.

the process comprising the steps of:

(a) reacting compound 1 with lithium hydroxide to produce compound 2a:

or

reacting compound 1 with lithium borohydride, followed by TEMPO-mediated oxidation to produce compound 2b:

(b) converting the carboxylic acid of 2a or the aldehyde of 2b to a heterocyclic ring to produce compound 3:

(c) debenzylating compound 3 to produce compound 4:

and

(d) reacting intermediate 4 with SO 3 .pyridine complex to produce compound 5:

2. The process of claim 1 , wherein compound of Formula (A-I) is the compound:

and

wherein

step (a) comprises reacting compound 1 with lithium hydroxide in THF/H 2 O to produce compound 2a; and

step (b) comprises the steps of:

(1) reacting compound 2a with tert-butyl hydrazinecarboxylate to produce the compound:

(2) reacting the product of step (1) with trifluoroacetic acid to produce the compound:

(3) reacting the product of step (2) with N-[(Dimethylamino)-1H-1,2,3-triazolo-[4,5-b]pyridin-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide (HATU) to produce the compound:

(4) reacting the product of step (3) with triflic anhydride to produce compound:

step (c) comprises the step of reacting the product of step (b) with Pd/C and H 2 to produce the compound:

and

step (d) comprises reacting the product of step (c) with SO 3 .pyridine complex to produce the compound:

3. The process of claim 1 , wherein compound 1 is produced by a process comprising the steps of:

(1) reacting the compound:

with the compound:

to produce the compound:

(2) reacting the product of step (1) with lithium hydroxide monohydrate and 2-mercaptoacetic acid to produce the compound:

(3) deprotecting the product of step (2) to produce the compound:

and

(4) reacting the product of step (3) with triphosgene such that compound 1 is formed.