US20020016323A1

US20020016323A1 - Oxazolidinone antibacterial agents having a thiocarbonyl functionality

Info

Publication number: US20020016323A1
Application number: US09/822,666
Authority: US
Inventors: Jackson Hester; Eldon Nidy; Salvatore Perricone; Toni-Jo Poel
Original assignee: Pharmacia and Upjohn Co
Current assignee: Pharmacia and Upjohn Co
Priority date: 1997-05-30
Filing date: 2001-03-30
Publication date: 2002-02-07
Also published as: US6362189B1; US6255304B1; US6537986B2; US6342513B1; US20010041728A1

Abstract

The present invention provides compounds of Formula 1

or pharmaceutical acceptable salts thereof wherein A, G and R₁are as defined in the claims which are antibacterial agents.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of co-pending application U.S. Ser. No. 09/080,751, filed May 18, 1998, which claims the benefit of provisional application U.S. Ser. No. 60/048,342, filed May 30, 1997, under 35 USC 119(e)(i).[0001]

BACKGROUND OF THE INVENTION

The present invention relates to new and useful oxazolidinone compounds and their preparations, and more particularly to oxazolidinone compounds in which the carbonyl functionality of —NH—C(O)—R is converted to a thiocarbonyl functionality, such as a thiourea —NH—C(S)—NH ₂, an alkyl thiourea —NH—C(S)—NH—(C_1-4alkyl), thioamide —NH—C(S)—(C_1-4alkyl) or —NH—C(S)—H.

Replacement of the oxygen atom with a sulfur atom has unexpectedly improved the antimicrobial properties of the compounds. The compounds are useful antimicrobial agents, effective against a number of human and veterinary pathogens, including Gram-positive aerobic bacteria such as multiply-resistant staphylococci and streptococci, Gram-negative organisms such as H. influenzae and M. catarrahlis as well as anaerobic organisms such as bacteroides and clostridia species, and acid-fast organisms such as Mycobacterium tuberculosis and Mycobacterium avium. The compounds are particularly useful because they are effective against the latter organisms which are known to be responsible for infection in persons with AIDS.

SUMMARY OF THE INVENTION

In one aspect the subject invention is a compound of the Formula I

or pharmaceutical acceptable salts thereof wherein:

G is

R ₁is

a) H,

b) NH ₂,

c) NH—C _1-4alkyl,

d) C _1-4alkyl,

e) —OC _1-4alkyl,

f) —S C _1-4alkyl,

g) C _1-4alkyl substituted with 1-3 F, 1-2 Cl, CN or —COOC_1-4alkyl,

h) C _3-6cycloalkyl,

i) N(C _1-4alkyl)₂or

j) N(CH ₂)_2-5;

A is

d) a 5-membered heteroaromatic moiety having one to three atoms selected from the group consisting of S, N, and O,

wherein the 5-membered heteroaromatic moiety is bonded via a carbon atom,

wherein the 5-membered heteroaromatic moiety can additionally have a fused-on benzene or naphthyl ring,

wherein the heteroaromatic moiety is optionally substituted with one to three R ₄₈,

e) a 6-membered heteroaromatic moiety having at least one nitrogen atom,

wherein the heteroaromatic moiety is bonded via a carbon atom,

wherein the 6-membered heteroaromatic moiety can additionally have a fused-on benzene or naphthyl ring,

wherein the heteroaromatic moiety is optionally substituted with one to three R ₅₅,

f) a β-carbolin-3-yl, or indolizinyl bonded via the 6-membered ring, optionally substituted with one to three R ₅₅,

wherein R ₂is

a) H,

b) F,

c) Cl,

d) Br,

e) C _1-3alkyl,

f) NO ₂, or

g) R ₂and R₃taken together are —O—(CH₂)_h—O—;

R ₃is

a) —S(═O) _iR₄,

b) —S(═O) ₂—N═S(O)_jR₅R₆,

c) —SC(═O)R ₇,

d) —C(═O)R ₈,

e) —C(═O)R ₉,

f) —C(═O)NR ₁₀R₁₁,

g) —C(═NR ₁₂)R₈,

h) —C(R ₈)(R₁₁)—OR₁₃,

i) —C(R ₉)(R₁₁)—OR₁₃,

j) —C(R ₈)(R₁₁)—OC(═O)R₁₃,

k) —C(R ₉)(R₁₁)—OC(═O)R₁₃,

l) —NR ₁₀R₁₁,

m) —N(R ₁₀)—C(═O)R₇,

n) —N(R ₁₀)—S(═O)_iR₇,

o) —C(OR ₁₄)(OR₁₅)R₈,

p) —C(R ₈)(R₁₆)—NR₁₀R₁₁, or

q) C _1-8alkyl substituted with one or more ═O other than at alpha position, —S(═O)_iR₁₇, —NR₁₀R₁₁, C_2-5alkenyl, or C_2-5alkynyl;

R ₄is

a) C _1-4alkyl optionally substituted with one or more halos, OH, CN, NR₁₀R₁₁, or —CO₂R₁₃,

b) C _2-4alkenyl,

c) —NR ₁₆R₁₈,

d) —N ₃,

e) —NHC(═O)R ₇,

f) —NR ₂₀C(═O)R₇,

g) —N(R ₁₉)₂,

h) —NR ₁₆R₁₉, or

i) —NR ₁₉R₂₀,

R ₅and R₆at each occurrence are the same or different and are

a) C _1-2alkyl, or

b) R ₅and R₆taken together are —(CH₂)_k—;

R ₇is C_1-4alkyl optionally substituted with one or more halos;

R ₈is

a) H, or

b) C _1-8alkyl optionally substituted with one or more halos, or C_3-8cycloalkyl;

R ₉is C_1-4alkyl substituted with one or more

a) —S(═O)R ₁₇,

b) —OR ₁₃,

c) —OC(═O)R ₁₃,

d) —NR ₁₀R₁₁, or

e) C _1-5alkenyl optionally substituted with CHO;

R ₁₀and R₁₁at each occurrence are the same or different and are

a) H,

b) C _1-4alkyl, or

c) C _3-8cycloalkyl;

R ₁₂is

a) —NR ₁₀R₁₁,

b) —OR ₁₀; or

c) —NHC(═O)R ₁₀;

R ₁₃is

a) H, or

b) C _1-4alkyl;

R ₁₄and R₁₅at each occurrence are the same or different and are

a) C _1-4alkyl, or

b) R ₁₄and R₁₅taken together are —(CH)_l—;

R ₁₆is

a) H,

b) C _1-4alkyl, or

c) C _3-8cycloalkyl;

R ₁₇is

a) C _1-4alkyl, or

b) C _3-8cycloalkyl;

R ₁₈is

a) H,

b) C _1-4alkyl,

c) C _2-4alkenyl,

d) C _3-4cycloalkyl,

e) —OR _1-3or

f) —NR ₂₁R₂₂;

R ₁₉is

a) Cl,

b) Br, or

c) I;

R ₂₀is a physiologically acceptable cation;

R ₂₁and R₂₂at each occurrence are the same or different and are

a) H,

b) C _1-4alkyl, or

c) —NR ₂₁R₂₂taken together are —(CH₂)_m—;

wherein R ₂₃and R₂₄at each occurrence are the same or different and are

a) H,

b) F,

c) Cl,

d) C _1-2alkyl,

e) CN

f) OH,

g) C _1-2alkoxy,

h) nitro, or

i) amino;

Q is

m) a diazinyl group optionally substituted with X and Y,

n) a triazinyl group optionally substituted with X and Y,

o) a quinolinyl group optionally substituted with X and Y,

p) a quinoxalinyl group optionally substituted with X and Y,

q) a naphthyridinyl group optionally substituted with X and Y,

Q and R ₂₄taken together are

wherein Z ¹is

a) —CH ₂—,

b) —CH(R ¹⁰⁴)—CH₂—,

c) —C(O)—, or

d) —CH ₂CH₂CH₂—;

wherein Z ²is

a) —O ₂S—,

b) —O—,

c) —N(R ¹⁰⁷)—,

d) —OS—, or

e) —S—;

wherein Z ³is

a) —O ₂S—,

b) —O—,

c) —OS—, or

d) —S—;

wherein A ¹is

a) H—, or

b) CH ₃;

wherein A ²is

a) H—,

b) HO—,

c) CH ₃—,

d) CH ₃O—,

e) R ¹⁰²O—CH₂—C(O)—NH—

f) R ¹⁰³O—C(O)—NH—,

g) (C ₁-C₂)alkyl-O—C(O)—,

h) HO—CH ₂—,

i) CH ₃O—NH—,

j) (C ₁-C₃)alkyl-O₂C—

k) CH ₃—C(O)—,

l) CH ₃—C(O)—CH₂—,

A ¹and A²taken together are:

wherein R ¹⁰²is

a) H—,

b) CH ₃—,

c) phenyl-CH ₂—, or

d) CH ₃C(O)—;

wherein R ¹⁰³is

a) (C ₁-C₃)alkyl-, or

b) phenyl-;

wherein R ¹⁰⁴is

a) H—, or

b) HO—;

wherein R ¹⁰⁵is

a) H—,

b) (C ₁-C₃)alkyl-,

c) CH ₂═CH—CH₂—, or

d) CH ₃—O—(CH₂)₂—;

wherein R ¹⁰⁶is

a) CH ₃—C(O)—,

b) H—C(O)—,

c) Cl ₂CH—C(O)—,

d) HOCH ₂—C(O)—,

e) CH ₃SO₂—,

g) F ₂CHC(O)—,

i) H ₃C—C(O)—O—CH₂—C(O)—,

j) H—C(O)—O—CH ₂—C(O)—,

l) HC≡C—CH ₂O—CH₂—C(O)—, or

m) phenyl-CH ₂—O—CH₂—C(O)—;

wherein R ¹⁰⁷is

a) R ¹⁰²O—C(R¹¹⁰)(R¹¹¹)—C(O)—,

b) R ¹⁰³O—C(O)—,

c) R ¹⁰⁸—C(O)—,

f) H ₃C—C(O)—(CH₂)₂—C(O)—,

g) R ¹⁰⁹—SO₂—,

i) HO—CH ₂—C(O)—,

j) R ¹¹⁶—(CH₂)₂—,

k) R ¹¹³—C(O)—O—CH₂—C(O)—,

l) (CH ₃)₂N—CH₂—C(O)—NH—,

m) NC—CH ₂—,

n) F ₂—CH—CH₂—, or

o) R ¹⁵⁰R¹⁵¹NSO₂

wherein R ¹⁰⁸is

a) H—,

b) (C ₁-C₄)alkyl,

c) aryl —(CH ₂)_p,

d) ClH ₂C—,

e) Cl ₂HC—,

f) FH ₂C—,

g) F ₂HC—,

h) (C ₃-C₆)cycloalkyl, or

i) CNCH ₂—.

wherein R ¹⁰⁹is

a) alkylC ₁-C₄,

b) —CH ₂Cl

c) —CH ₂CH═CH₂,

d) aryl, or

e) —CH ₂CN;

wherein R ¹¹⁰and R¹¹¹are independently

a) H—,

b) CH ₃—; or

wherein R ¹¹²is

a) H—,

b) CH ₃O—CH₂O—CH₂—, or

c) HOCH ₂—;

wherein R ¹¹³is

a) CH ₃—,

b) HOCH ₂—,

c) (CH ₃)₂N-phenyl, or

d) (CH ₃)₂N—CH₂—;

wherein R ¹¹⁴is

a) HO—,

b) CH ₃O—,

c) H ₂N—,

d) CH ₃O—C(O)—O—,

e) CH ₃—C(O)—O—CH₂—C(O)—O—,

f) phenyl-CH ₂—O—CH₂—C(O)—O—,

g) HO—(CH ₂)₂—O—,

h) CH ₃O—CH₂—O—(CH₂)₂—O—, or

i) CH ₃O—CH₂—;

wherein R ¹¹³is

a) CH ₃—,

b) HOCH ₂—,

c) (CH ₃)₂N-phenyl, or

d) (CH ₃)₂N—CH₂—;

wherein R ¹¹⁵is

a) H—, or

b) Cl—;

wherein R ¹¹⁶is

a) HO—

b) CH ₃O—, or

c) F;

wherein R ¹⁵⁰and R¹⁵¹are each H or alkyl C₁-C₄or R¹⁵⁰and R¹⁵¹taken together with the nitrogen atom to which each is attached form a monocyclic heterocyclic ring having from 3 to 6 carbon atoms;

B is an unsaturated 4-atom linker having one nitrogen and three carbons;

M is

a) H,

b) C _1-8alkyl,

c) C _3-8cycloalkyl,

d) —(CH ₂)_mOR₁₃, or

e) —(CH ₂)_h—NR₂₁R₂₂;

Z is

a) O,

b) S, or

c) NM;

W is

a) CH,

b) N, or

c) S or O when Z is NM;

Y is

a) H,

b) F,

c) Cl,

d) Br,

e) C _1-3alkyl, or

f) NO ₂;

X is

a) H,

b) —CN,

c) OR ₂₇,

d) halo,

e) NO ₂,

f) tetrazoyl,

g) —SH,

h) —S(═O) _iR₄,

i) —S(═O) ₂—N═S(O)_jR₅R₆,

j) —SC(═O)R ₇,

k) —C(═O)R ₂₅,

l) —C(═O)NR ₂₇R₂₈,

m) —C(═NR ₂₉)R₂₅,

n) —C(R ₂₅)(R₂₈)—OR₁₃,

o) —C(R ₂₅)(R₂₈)—OC(═O)R₁₃,

p) —C(R ₂₈)(OR₁₃)—(CH₂)_h—NR₂₇R₂₈,

q) —NR ₂₇R₂₈,

r) —N(R ₂₇)C(═O)R₇,

s) —N(R ₂₇)—S(═O)_iR₇,

t) —C(OR ₁₄)(OR₁₅)R₂₈,

u) —C(R ₂₅)(R₁₆)—NR₂₇R₂₆, or

v) C _1-8alkyl substituted with one or more halos, OH, ═O other than at alpha position, —S(═O)_iR₁₇, —NR₂₇R₂₈, C_2-5alkenyl, C_2-5alkynyl, or C_3-8cycloalkyl;

R ₄, R₅, R₆, R₇, R₁₃, R₁₄, R₁₅, R₁₆, and R₁₇are the same as defined above;

R ₂₅is

a) H,

b) C _1-8alkyl optionally substituted with one or more halos, C_3-8cycloalkyl, C_1-4alkyl substituted with one or more of —S(═O)_iR₁₇, —OR₁₃, or OC(═O)R₁₃, NR₂₇R₂₈, or

c) C _2-5alkenyl optionally substituted with CHO, or CO₂R₁₃;

R ₂₆is

a) R ₂₈, or

b) NR ₂₇N₂₈;

R ₂₇and R₂₈at each occurrence are the same or different and are

a) H,

b) C _1-8alkyl,

c) C _3-8cycloalkyl,

d) —(CH ₂)_mOR₁₃,

e) —(CH ₂)_h—NR₂₁R₂₂, or

f) R ₂₇and R₂₈taken together are —(CH₂)₂O(CH₂)₂—, —(CH₂)_hCH(COR₇)—, or —(CH₂)₂N(CH₂)₂(R₇);

R ₂₉is

a) —NR ₂₇R₂₈,

b) —OR ₂₇, or

c) —NHC(═O)R ₂₈;

wherein R ₃₀is

a) H,

b) C _1-8alkyl optionally substituted with one or more halos, or

c) C _1-8alkyl optionally substituted with one or more OH, or C_1-6alkoxy;

wherein E is

a) NR ₃₉,

b) —S(═O) _i, or

c) O;

R ₃₈is

a) H,

b) C _1-6alkyl,

c) —(CH ₂)_q-aryl, or

d) halo;

R ₃₉is

a) H,

b) C _1-6alkyl optionally substituted with one or more OH, halo, or —CN,

c) —(CH ₂)_q-aryl,

d) —CO ₂R₄₀,

e) —COR ₄₁,

f) —C(═O)—(CH ₂)_q—C(═O)R₄₀,

g) —S(═O) ₂—C_1-6alkyl,

h) —S(═O) ₂—(CH₂)_q-aryl, or

i) —(C═O) _j-Het;

R ₄₀is

a) H,

b) C _1-6alkyl optionally substituted with one or more OH, halo, or —CN,

c) —(CH ₂)_q-aryl, or

d) —(CH ₂)_q—OR₄₂;

R ₄₁is

a) C _1-6alkyl optionally substituted with one or more OH, halo, or —CN,

b) —(CH ₂)_q-aryl, or

c) —(CH ₂)_q—OR₄₂;

R ₄₂is

a) H,

b) C _1-6alkyl,

c) —(CH ₂)_q-aryl, or

d) —C(═O)—C _1-6alkyl;

aryl is

a) phenyl,

b) pyridyl, or

c) napthyl; a to c optionally substituted with one or more halo, —CN, OH, SH, C _1-6alkyl, C_1-6alkoxy, or C_1-6alkylthio;

wherein R ₄₃is

a) H,

b) C _1-2alkyl,

c) F, or

d) OH;

R ₄₄is

a) H,

b) CF ₃,

c) C _1-3alkyl optionally substituted with one or more halo,

d) phenyl optionally substituted with one or more halo,

e) R ₄₄and R₄₅taken together are a 5-, 6-, or 7-membered ring of the formula,

or

f) R ₄₄and R₄₅taken together are —(CH₂)_k—, when R₄₆is an electron withdrawing group;

R ₄₅and R₄₆at each occurrence are the same or different and are

a) an electron-withdrawing group,

b) H,

c) CF ₃,

d) C _1-3alkyl optionally substituted with one halo,

e) phenyl, provided at least one of R ₄₅or R₄₆is an electron-withdrawing group, or

f) R ₄₅and R₄₆taken together are a 5-, 6-, 7-membered ring of the formula

U is

a) CH ₂,

b) O,

c) S, or

d) NR ₄₇;

R ₄₇is

a) H, or

b) C _1-5alkyl;

wherein R ₄₈is

a) carboxyl,

b) halo,

c) —CN,

d) mercapto,

e) formyl,

f) CF ₃,

g) —NO ₂,

h) C _1-6alkoxy,

i) C _1-6alkoxycarbonyl,

j) C _1-6alkythio,

k) C _1-6acyl,

l) —NR ₄₉R₅₀,

m) C _1-6alkyl optionally substituted with OH, C_1-5alkoxy, C_1-5acyl, or —NR₄₉R₅₀,

n) C _2-8alkenylphenyl optionally substituted with one or two R₅₁,

o) phenyl optionally substituted with one or two R ₅₁,

p) a 5-, or 6-membered (un)saturated heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, optionally substituted with one or two R ₅₁, or

R ₄₉and R₅₀at each occurrence are the same or different and are

a) H,

b) C _1-4alkyl,

c) C _5-6cycloalkyl, or

d) R ₄₉and R₅₀taken together with the nitrogen atom is a 5-, 6-membered saturated heterocyclic moiety which optionally has a further hetero atom selected from the group consisting of S, N, and O, and can in turn be optionally substituted with, including on the further nitrogen atom, C_1-3alkyl, or C_1-3acyl;

R ₅₁is

a) carboxyl,

b) halo,

c) —CN,

d) mercapto,

e) formyl,

f) CF ₃,

g) —NO ₂,

h) C _1-6alkoxy,

i) C _1-6alkoxycarbonyl,

j) C _1-6alkythio,

k) C _1-6acyl,

l) C _1-6alkyl optionally substituted with OH, C_1-5alkoxy, C_1-5acyl, or —NR₄₉R₅₀,

m) phenyl,

n) —C(═O)NR ₅₂R₅₃,

o) —NR ₄₉R₅₀,

p) —N(R ₅₂)(—SO₂R₅₄),

q) —SO ₂—NR₅₂R₅₃, or

r) —S(═O) ₁R₅₄;

R ₅₂and R₅₃at each occurrence are the same or different and are

a) H,

b) C _1-6alkyl, or

c) phenyl;

R ₅₄is

a) C _1-4alkyl, or

b) phenyl optionally substituted with C _1-4alkyl;

wherein R ₅₅is

a) carboxyl,

b) halo,

c) —CN,

d) mercapto,

e) formyl,

f) CF ₃,

g) —NO ₂,

h) C _1-6alkoxy,

i) C _1-6alkoxycarbonyl,

j) C _1-6alkythio

k) C _1-6acyl,

l) —NR ₅₆R₅₇,

m) C _1-6alkyl optionally substituted with OH, C_1-5alkoxy, C_1-5acyl, or —NR₅₆R₅₇,

n) C _2-8alkenylphenyl optionally substituted with one or two R₅₈,

o) phenyl optionally substituted with one or two R ₅₈,

p) a 5- or 6-membered (un)saturated heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, optionally substituted with one or two R ₅₈, or

R ₅₆and R₅₇at each occurrence are the same or different and are

a) H,

b) formyl,

c) C _1-4alkyl,

d) C _1-4acyl,

e) phenyl,

f) C _3-6cycloalkyl, or

g) R ₅₆and R₅₇taken together with the nitrogen atom is a 5-, 6-membered saturated heterocyclic moiety which optionally has a further hetero atom selected from the group consisting of S, N, and O, and can in turn be optionally substituted with, including on the further nitrogen atom, phenyl, pyrimidyl, C_1-3alkyl, or C_1-3acyl;

R ₅₈is

a) carboxyl,

b) halo,

c) —CN,

d) mercapto,

e) formyl,

f) CF ₃,

g) —NO ₂,

h) C _1-6alkoxy,

i) C _1-6alkoxycarbonyl,

j) C _1-6alkythio,

k) C _1-6acyl,

l) phenyl,

m) C _1-6alkyl optionally substituted with OH, azido, C_1-5alkoxy, C_1-5acyl, —NR₆₅R₆₆, —SR₆₇, —O—SO₂R₆₈, or

n) —C(═O)NR ₅₉R₆₀,

o) —NR ₅₆R₅₇,

p) —N(R ₅₉)(—SO₂R₅₄),

q) —SO ₂—NR₅₉R₆₀,

r) —S(═O) _iR₅₄,

s) —CH═N—R ₆₁, or

t) —CH(OH)—SO ₃R₆₄;

R ₅₄is the same as defined above;

R ₅₉and R₆₀at each occurrence are the same or different and are

a) H,

b) C _1-6alkyl,

c) phenyl, or

d) tolyl;

R ₆₁is

a) OH,

b) benzyloxy,

c) —NH—C(═O)—NH ₂,

d) —NH—C(═S)—NH ₂, or

e) —NH—C(═NH)—NR ₆₂R₆₃;

R ₆₂and R₆₃at each occurrence are the same or different and are

a) H, or

b) C _1-4alkyl optionally substituted with phenyl or pyridyl;

R ₆₄is

a) H, or

b) a sodium ion;

R ₆₅and R₆₆at each occurrence are the same or different and are

a) H,

b) formyl,

c) C _1-4alkyl,

d) C _1-4acyl,

e) phenyl,

f) C _3-6cycloalkyl,

g) R ₆₅and R₆₆taken together are a 5-, 6-membered saturated heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, optionally substituted with, including on the nitrogen atom, phenyl, pyrimidyl, C_1-3alkyl, or C_1-3acyl,

h) —P(O)(OR ₇₀)(OR₇₁), or

i) —SO ₂—R₇₂;

R ₆₇is

R ₆₈is C_1-3alkyl;

R ₆₉is

a) C _1-6alkoxycarbonyl, or

b) carboxyl;

R ₇₀and R₇₁at each occurrence are the same or different and are

a) H, or

b) C _1-3alkyl;

R ₇₂is

a) methyl,

b) phenyl, or

c) tolyl;

wherein K is

a) O, or

b) S;

R ₇₃, R₇₄, R₇₅, R₇₆, and R₇₇at each occurrence are the same or different and are

a) H,

b) carboxyl,

c) halo,

d) —CN,

e) mercapto,

f) formyl,

g) CF ₃,

h) —NO ₂,

i) C _1-6alkoxy,

j) C _1-6alkoxycarbonyl,

k) C _1-6alkythio,

l) C _1-6acyl,

m) —NR ₇₈R₇₉,

n) C _1-6alkyl optionally substituted with OH, C_1-5alkoxy, C_1-5acyl, —NR₇₈R₇₉, —N(phenyl)(CH₂—CH₂—OH), —O—CH(CH₃)(OCH₂CH₃), or —O-phenyl-[para-NHC(═O)CH₃],

o) C _2-8alkenylphenyl optionally substituted with R₅₁,

p) phenyl optionally substituted with R ₅₁, or

q) a 5-, or 6-membered (un)saturated heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, optionally substituted with R ₅₁;

R ₅₁is the same as defined above;

R ₇₈and R₇₉at each occurrence are the same or different and are

a) H,

b) C _1-4alkyl,

c) phenyl, or

d) R ₇₈and R₇₉taken together with the nitrogen atom is a 5-, 6-membered saturated heterocyclic moiety which optionally has a further hetero atom selected from the group consisting of S, N, and O, and can in turn be optionally substituted with, including on the further nitrogen atom, C_1-3alkyl, or C_1-3acyl;

wherein T is

a) O,

b) S, or

c) SO ₂;

R ₇₅, R₇₆, and R₇₇are the same as defined above;

R ₈₀is

a) H,

b) formyl,

c) carboxyl,

d) C _1-6alkoxycarbonyl,

e) C _1-8alkyl,

f) C _2-8alkenyl,

wherein the substituents (e) and (f) can be optionally substituted with OH, halo, C _1-6alkoxy, C_1-6acyl, C_1-6alkylthio or C_1-6alkoxycarbonyl, or phenyl optionally substituted with halo,

g) an aromatic moiety having 6 to 10 carbon atoms optionally substituted with carboxyl, halo, —CN, formyl, CF ₃, —NO₂, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl, C_1-6alkylthio, or C_1-6alkoxycarbonyl;

h) —NR ₈₁R₈₂,

i) —OR ₉₀,

j) —S(═O) _i—R₉₁,

k) —SO ₂—N(R₉₂)(R₉₃), or

l) a radical of the following formulas:

R ₈₁and R₈₂at each occurrence are the same or different and are

a) H,

b) C _3-6cycloalkyl,

c) phenyl,

d) C _1-6acyl,

e) C _1-8alkyl optionally substituted with OH, C_1-6alkoxy which can be substituted with OH, a 5-, or 6-membered aromatic heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, phenyl optionally substituted with OH, CF₃, halo, —NO₂, C_1-4alkoxy, —NR₈₃R₈₄, or

V is

a) O,

b) CH ₂, or

c) NR ₈₇;

R ₈₃and R₈₄at each occurrence are the same or different and are

a) H, or

b) C _1-4alkyl;

R ₈₅is

a) OH,

b) C _1-4alkoxy, or

c) —NR ₈₈R₈₉;

R ₈₆is

a) H, or

b) C _1-7alkyl optionally substituted with indolyl, OH, mercaptyl, imidazoly, methylthio, amino, phenyl optionally substituted with OH, —C(═O)—NH₂, —CO₂H, or —C(═NH)—NH₂;

R ₈₇is

a) H,

b) phenyl, or

c) C _1-6alkyl optionally substituted by OH;

R ₈₈and R₈₉at each occurrence are the same or different and are

a) H,

b) C _1-5alkyl

c) C _3-6cycloalky, or

d) phenyl;

R ₉₀is

a) C _1-8alkyl optionally substituted with C_1-6alkoxy or C_1-6hydroxy, C_3-6cycloalkyl, a 6-membered aromatic optionally benzo-fused heterocyclic moiety having one to three nitrogen atoms, which can in turn be substituted with one or two —NO₂, CF₃, halo, —CN, OH, C_1-5alkyl, C_1-5alkoxy, or C_1-5acyl;

c) phenyl, or

d) pyridyl;

R ₉₁is

a) C _1-16alkyl,

b) C _2-16alkenyl,

wherein the substituents (a) and (b) can be optionally substituted with C _1-6alkoxycarbonyl, or a 5-, 6-, 7-membered aromatic heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O,

c) an aromatic moiety having 6 to 10 carbon atoms, or

d) a 5-, 6-, 7-membered aromatic heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O,

wherein the substituents (c) and (d) can be optionally substituted with carboxyl, halo, —CN, formyl, CF ₃, —NO₂, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl, C_1-6alkylthio, or C_1-6alkoxycarbonyl;

R ₉₂and R₉₃at each occurrence are the same or different and are

a) H,

b) phenyl,

c) C _1-6alkyl, or

d) benzyl;

R ₉₄and R₉₅at each occurrence are the same or different and are

a) H,

b) OH,

c) C _1-6alkyl optionally substituted with —NR₈₃R₈₄, or

d) R ₉₄and R₉₅taken together are ═O;

R ₉₆is

a) an aromatic moiety having 6 to 10 carbon atoms,

b) a 5-, or 6-membered aromatic optionally benzo-fused heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O,

wherein the substituents (a) and (b) which can in turn be substituted with one or three —NO ₂, CF₃, halo, —CN, OH, phenyl, C_1-5alkyl, C_1-5alkoxy, or C_1-5acyl,

c) morpholinyl,

d) OH,

e) C _1-6alkoxy,

f) —NR ₈₃R₈₄,

g) —C(═O)—R ₉₇, or

R ₉₇is

a) morpholinyl,

b) OH, or

c) C _1-6alkoxy;

h is 1, 2, or 3;

i is 0, 1, or 2;

j is 0 or 1;

k is 3, 4, or 5;

l is 2 or 3;

m is 4 or 5;

n is 0, 1, 2, 3, 4, or 5;

p is 0, 1, 2, 3, 4, or 5; with the proviso that n and p together are 1, 2, 3, 4, or 5;

q is 1, 2, 3, or 4;

r is 2, 3, or 4;

t is 0, 1, 2, 3, 4, 5, or 6;

u is 1 or 2;

w is 0, 1, 2, or 3.

DETAILED DESCRIPTION OF THE INVENTION

The new compounds of the invention can be prepared using known compounds and intermediates of oxazolidinones, isoxazolines and butyolactones as intermediates and synthetic methods known in the art. Thioamides of the invention can typically be prepared by the reaction of the corresponding amide with Lawesson's reagent.

Compounds disclosed in the following publications are suitable intermediates for preparation of the compounds of this invention and are hereby incorporated by reference for their disclosure of suitable compounds that can be converted to the subject thiocarbonyl derivatives.

U.S. Pat. Nos. 5,225,565; 5,182,403; 5,164,510; 5,247,090; 5,231,188; 5,565,571; 5,547,950; and 5,523,403.

PCT Application and publications PCT/US93/04850, WO94/01110; PCT/US94/08904, WO95/07271; PCT/US95/02972, WO95/25106; PCT/US95/10992, WO96/13502; PCT/US96/05202, WO96/35691; PCT/US96/12766; PCT/US96/13726; PCT/US96/14135; PCT/US96/17120; PCT/US96/19149; PCT/US97/01970; PCT/US95/12751, WO96/15130; and PCT/US96/00718, WO96/23788.

Chemical conversion techniques for converting various intermediates having a CH ₂NH₂on the oxazolidinone ring to CH₂NH—C(S)—CH₃is disclosed by Hartke, K, Barrmeyer, S., J. prakt. Chem. 1996, 338, 251-6. Similarly, conversion of CH₂NHC(═O)CH₃to CH₂NHC(S)NHCH₃is reported by Cava, M. P.; Levinson, M. I., Thionation Reactions of Lawesson's Reagents, Tetrahedron 1985, 41, 5061-87.

For the purpose of the present invention, the carbon content of various hydrocarbon containing moieties is indicated by a prefix designating the minimum and maximum number of carbon atoms in the moiety, i.e., the prefix C _i-jdefines the number of carbon atoms present from the integer “i” to the integer “j”, inclusive. Thus, C_1-4alkyl refers to alkyl of 1-4 carbon atoms, inclusive, or methyl, ethyl, propyl, butyl and isomeric forms thereof.

The terms “C _1-2alkyl”, “C_1-3alkyl”, “C_1-4alkyl”, “C_1-5alkyl”, “C_1-6alkyl”, “C_1-8alkyl”, and “C_1-16alkyl” refer to an alkyl group having one to two, one to three, one to four, one to five, one to six, one to eight, or one to sixteen carbon atoms respectively such as, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl and their isomeric forms thereof.

The terms “C _2-4alkenyl”, “C_2-5alkenyl”, “C_2-8alkenyl”, “C_2-14alkenyl” and “C_2-16alkenyl” refer to at least one double bond alkenyl group having two to four, two to five, two to eight, two to fourteen, or two to sixteen carbon atoms, respectively such as, for example, ethenyl, propenyl, butenyl, pentenyl, pentdienyl, hexenyl, hexdienyl, heptenyl, heptdienyl, octenyl, octdienyl, octatrienyl, nonenyl, nonedienyl, nonatrienyl, undecenyl, undecdienyl, dodecenyl, tridecenyl, tetradecenyl and their isomeric forms thereof.

The terms “C _2-5alkynyl”, “C_2-8alkynyl”, and “C_2-10alkynyl” refer to at least one triple bond alkynyl group having two to five, two to eight, or two to ten carbon atoms respectively such as, for example, ethynyl, propynyl, butynyl, pentynyl, pentdiynyl, hexynyl, hexdiynyl, heptynyl, heptdiynyl, octynyl, octdiynyl, octatriynyl, nonynyl, nonediynyl, nonatriynyl and their isomeric forms thereof.

The terms “C _3-4cycloalkyl”, “C_3-6cycloalkyl”, “C_5-6cycloalkyl”, and “C_3-8cycloalkyl” refer to a cycloalkyl having three to four, three to six, five to six, or three to eight carbon atoms respectively such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and their isomeric forms thereof.

The terms “C _1-4alkoxy”, “C_1-6alkoxy”, and “C_1-8alkoxy” refer to an alkyl group having one to four, one to six, or one to eight carbon atoms respectively attached to an oxygen atom such as, for example, methoxy, ethoxy, propyloxy, butyloxy, pentyloxy, hexyloxy, heptyloxy, or octyloxy and their isomeric forms thereof.

The terms “C _1-6alkylamino”, and “C_1-8alkylamino” refer to an alkyl group having one to six, or one to eight carbon atoms respectively attached to an amino moiety such as, for example, methylamino, ethylamino, propylamino, butylamino, pentylamino, hexylamino, heptylamino, or octoylamino and their isomeric forms thereof.

The terms “C _1-6dialkylamino”, and “C_1-8dialkylamino” refer to two alkyl groups having one to six, or one to eight carbon atoms respectively attached to an amino moiety such as, for example, dimethylamino, methylethylamino, diethylamino, dipropylamino, methypropylamino, ethylpropylamino, dibutylamino, dipentylamino, dihexylamino, methylhecylamino, diheptylamino, or dioctoylamino and their isomeric forms thereof.

The terms “C _1-3acyl”, “C_1-4acyl”, “C_1-5acyl”, “C_1-6acyl”, “C_1-8acyl”, and “C_2-8acyl” refer to a carbonyl group having an alkyl group of one to three, one to four, one to five, one to six, one to eight, or two to eight carbon atoms.

The terms “C _1-4alkoxycarbonyl”, “C_1-6alkoxycarbonyl”, and “C_1-8alkoxycarbonyl” refer to an ester group having an alkyl group of one to four, one to six, or one to eight carbon atoms.

The term “C _1-8alkyl phenyl” refers to an alkyl group having one to eight carbon atoms and isomeric forms thereof which is substituted with at least one phenyl radical.

The term “C _2-8alkenyl phenyl” refers to a at least one double bond alkenyl group having one to eight carbon atoms and isomeric forms thereof which is substituted with at least one phenyl radical.

The term “C _1-8alkyl pyridyl” refers to an alkyl group having one to eight carbon atoms and isomeric forms thereof which is substituted with at least one pyridyl radical.

The term “C _1-8hydroxyl” refers to an alkyl group having one to eight carbon atoms and isomeric forms thereof attached to a hydroxy group.

The term “C _1-8alkylsulfonyl” refers to an alkyl group having one to eight carbon atoms and isomeric forms thereof attached to a SO₂moiety.

The term “C _1-6alkylthio” refers to an alkyl group having one to six carbon atoms and isomeric forms thereof attached to a sulfur atom.

The term “Het” refers to 5 to 10 membered saturated, unsaturated or aromatic heterocyclic rings containing one or more oxygen, nitrogen, and sulfur forming such groups as, for example, pyridine, thiophene, furan, pyrazoline, pyrimidine, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 3-pyrazinyl, 2-quinolyl, 3-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 2-quinazolinyl, 4-quinazolinyl, 2-quinoxalinyl, 1-phthalazinyl, 4-oxo-2-imidazolyl, 2-imidazolyl, 4-imidazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 4-oxo-2-oxazolyl, 5-oxazolyl, 4,5,-dihydrooxazole, 1,2,3-oxathiole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 3-isothiazole, 4-isothiazole, 5-isothiazole, 2-indolyl, 3-indolyl, 3-indazolyl, 2-benzoxazolyl, 2-benzothiazolyl, 2-benzimidazolyl, 2-benzofuranyl, 3-benzofuranyl, benzoisothiazole, benzisoxazole, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 3-isopyrrolyl, 4-isopyrrolyl, 5-isopyrrolyl, 1,2,3,-oxathiazole-1-oxide, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 5-oxo-1,2,4-oxadiazol-3-yl, 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 3-oxo-1,2,4-thiadiazol-5-yl, 1,3,4-thiadiazol-5-yl, 2-oxo-1,3,4-thiadiazol-5-yl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,3,4-tetrazol-5-yl, 5-oxazolyl, 1-pyrrolyl, 1-pyrazolyl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, 1-tetrazolyl, 1-indolyl, 1-indazolyl, 2-isoindolyl, 7-oxo-2-isoindolyl,1-purinyl, 3-isothiazolyl, 4-isothiazolyl and 5-isothiazolyl, 1,3,4,-oxadiazole, 4-oxo-2-thiazolinyl, or 5-methyl-1,3,4-thiadiazol-2-yl, thiazoledione, 1,2,3,4-thiatriazole, 1,2,4-dithiazolone. Each of these moieties may be substituted as appropriate.

The term halo refers to fluoro, chloro, bromo, or iodo.

The compounds of the present invention can be converted to their salts, where appropriate, according to conventional methods.

The term “pharmaceutically acceptable salts” refers to acid addition salts useful for administering the compounds of this invention and include hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, acetate, propionate, lactate, mesylate, maleate, malate, succinate, tartrate, citric acid, 2-hydroxyethyl sulfonate, fumarate and the like. These salts may be in hydrated form.

When Q is the structure of

the dotted line in the heterocyclic ring means that this bond can be either single or double. In the case where the dotted line is a double bond, the R ₃₉group will not be present.

The compounds of Formula I of this invention contain a chiral center at C5 of the isoxazoline ring, and as such there exist two enantiomers or a racemic mixture of both. This invention relates to both the enantiomers, as well as mixtures containing both the isomers. In addition, depending on substituents, additional chiral centers and other isomeric forms may be present in any of A or R ₁group, and this invention embraces all possible stereoisomers and geometric forms in these groups.

The compounds of this invention are useful for treatment of microbial infections in humans and other warm blooded animals, under both parenteral and oral administration.

The pharmaceutical compositions of this invention may be prepared by combining the compounds of this invention with a solid or liquid pharmaceutically acceptable carrier and, optionally, with pharmaceutically acceptable adjuvants and excipients employing standard and conventional techniques. Solid form compositions include powders, tablets, dispersible granules, capsules, cachets and suppositories. A solid carrier can be at least one substance which may also function as a diluent, flavoring agent, solubilizer, lubricant, suspending agent, binder, tablet disintegrating agent, and encapsulating agent. Inert solid carriers include magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, cellulosic materials, low melting wax, cocoa butter, and the like. Liquid form compositions include solutions, suspensions and emulsions. For example, there may be provided solutions of the compounds of this invention dissolved in water and water-propylene glycol and water-polyethylene glycol systems, optionally containing suitable conventional coloring agents, flavoring agents, stabilizers and thickening agents.

Preferably, the pharmaceutical composition is provided employing conventional techniques in unit dosage form containing effective or appropriate amounts of the active component, that is, the compound according to this invention.

The quantity of active component, that is the compound according to this invention, in the pharmaceutical composition and unit dosage form thereof may be varied or adjusted widely depending upon the particular application, the potency of the particular compound, the desired concentration. Generally, the quantity of active component will range between 0.5% to 90% by weight of the composition.

In therapeutic use for treating, or combatting, bacterial infections in warm-blooded animals, the compounds or pharmaceutical compositions thereof will be administered orally, parenterally and/or topically at a dosage to obtain and maintain a concentration, that is, an amount, or blood-level of active component in the animal undergoing treatment which will be antibacterially effective. Generally, such antibacterially effective amount of dosage of active component will be in the range of about 0.1 to about 100, more preferably about 3.0 to about 50 mg/kg of body weight/day. It is to be understood that the dosages may vary depending upon the requirements of the patient, the severity of the bacterial infection being treated, and the particular compound being used. Also, it is to be understood that the initial dosage administered may be increased beyond the above upper level in order to rapidly achieve the desired blood-level or the initial dosage may be smaller than the optimum and the daily dosage may be progressively increased during the course of treatment depending on the particular situation. If desired, the daily dose may also be divided into multiple doses for administration, e.g., 2-4 four times per day.

When the compounds according to this invention are administered parenterally, i.e., by injection, for example, by intravenous injection or by other parenteral routes of administration. Pharmaceutical compositions for parenteral administration will generally contain a pharmaceutically acceptable amount of the compound or a soluble salt (acid addition salt or base salt) dissolved in a pharmaceutically acceptable liquid carrier such as, for example, water-for-injection and a buffer to provide a suitably buffered isotonic solution, for example, having a pH of about 3.5-6. Suitable buffering agents include, for example, trisodium orthophosphate, sodium bicarbonate, sodium citrate, N-methylglucamine, L(+)-lysine and L(+)-arginine to name but a few representative buffering agents. The compound of this invention generally will be dissolved in the carrier in an amount sufficient to provide a pharmaceutically acceptable injectable concentration in the range of about 1 mg/mL to about 400 mg/mL of solution. The resulting liquid pharmaceutical composition will be administered so as to obtain the above-mentioned antibacterially effective amount of dosage. The compounds according to this invention are advantageously administered orally in solid and liquid dosage forms.

As a topical treatment an effective amount of Formula I is admixed in a pharmaceutically acceptable gel or cream vehicle that can be applied to the patient's skin at the area of treatment. Preparation of such creams and gels is well known in the art and can include penetration enhancers.

MIC Test Method

The in vitro MICs of test compounds were determined by a standard agar dilution method. A stock drug solution of each analog is prepared in the preferred solvent, usually DMSO:H ₂O (1:3). Serial 2-fold dilutions of each sample are made using 1.0 ml aliquots of sterile distilled water. To each 1.0 ml aliquot of drug is added 9 ml of molten Mueller Hinton agar medium. The drug-supplemented agar is mixed, poured into 15×100 mm petri dishes, and allowed to solidify and dry prior to inoculation.

Vials of each of the test organisms are maintained frozen in the vapor phase of a liquid nitrogen freezer. Test cultures are grown overnight at 35° C. on the medium appropriate for the organism. Colonies are harvested with a sterile swab, and cell suspensions are prepared in Trypticase Soy broth (TSB) to equal the turbidity of a 0.5 McFarland standard. A 1:20 dilution of each suspension is made in TSB. The plates containing the drug supplemented agar are inoculated with a 0.001 ml drop of the cell suspension using a Steers replicator, yielding approximately 10 ⁴to 10⁵cells per spot. The plates are incubated overnight at 35° C.

Following incubation the Minimum Inhibitory Concentration (MIC μg/ml), the lowest concentration of drug that inhibits visible growth of the organism, is read and recorded. The data is shown in Tables I and II.

TABLE 1


	Oxazolidinone MIC Values
	(Gram+)

	SAUR	SEPI	EFAE	SPNE	SPYO
Structure	9213	12084	9217	9912	152

Comparison*
	16	4	8	.5	1

Example 3
	4	1	2	.25	.5

Comparison*
	2	1	2	.5	1

Example 1
	1	.25	.5	.13	.13

Example 5
	1	.25	.5	<.125	.25

Example 6
	2	1	2	.5	1

Comparison*
	.5	.25	1	.13	.25

Example 2
	8	2	4	2	4

TABLE II


	SAUR	SEPI	EFAB	SPNE	SPYO	HINF	MCAT	EFAE
Example No.	9213 MIC	30593 MIC	12712 MIC	9912 MIC	152 MIC	30063 MIC	30610 MIC	9217 MIC

1	1	0.25	0.5	<0.125	<0.125	8	1	0.5
2	8	4	8	2	4	>16	>16	4
3	4	1	1	0.25	0.5	16	4	2
5	1	0.5	0.5	<0.125	0.25	4	2	0.5
6	2	2	2	0.5	1	16	8	2
7	0.5	0.25	0.5	<0.125	0.25	4	1	0.5
8	2	1	0.5	<0.125	0.25	4	2	0.5
9	0.5	0.25	0.25	<0.125	<0.125	2	0.5	0.25
10	2	1	0.5	<0.125	0.25	2	1	1
11	0.25	0.25	0.25	<0.125	0.25	2	1	0.25
12	1	0.5	0.25	<0.125	<0.125	1	0.5	0.5
13	1	1	2	0.5	1	>16	8	2
14	1	0.5	1	0.25	0.5	8	1	1
15	32	16	32	4	8	>64	64	32
16	8	8	16	2	8	>64	32	16
17	2	2	4	1	2	64	16	4
18	2	1	2	<0.5	1	32	4	2
19	32	16	32	16	16	64	32	32
21	4	4	8	2	4	64	16	8
22, 23	0.5	0.5	1	<0.125	0.25	4	2	1
24	1	0.25	0.5	<0.125	0.25	4	2	0.5
25	0.5	0.25	0.5	<0.125	<0.125	2	2	0.5
26	1	0.5	1	0.25	0.5	16	2	1
27	0.5	0.5	0.5	<0.125	0.25	4	2	1
28	0.5	0.25	0.5	0.25	0.25	2	1	0.5
29	0.25	0.25	0.25	<0.125	<0.125	2	0.5	0.25
30	4	1	0.5	<0.125	0.25	8	2	1
31	2	1	1	<0.125	0.25	4	1	1
32	16	2	2	0.25	0.25	8	2	4
33	4	2	1	0.25	0.25	4	2	4
34	2	1	2	0.5	1	>16	4	2
35	1	0.5	1	0.25	0.5	16	2	1

As shown in Scheme 1, the intermediates II for the compounds of this invention are also intermediates disclosed in the oxazolidinone patents and published applications hereinabove incorporated by reference. The intermediates IV for this invention are final products (Examples) from the oxazolidinone patents and published applications hereinabove incorporated by reference.

As shown in Scheme 1, Step 1, and illustrated in Example 5, the isothiocyanates III can be conveniently prepared by allowing the amine intermediates (II) to react with 1,1′-thiocarbonyldi-2(1H)-pyridone in solvents such as methylene chloride at 0 to 25° C. The thioureas (Ia, R′=H, alkyl _1-4) can then be prepared as shown in Step 2 by the reaction of III with ammonia or the appropriate primary amines in solvents such as 1,4-dioxane or tetrahydrofuran at 0-50° C. Alternatively, as illustrated in Example 6 and shown in Step 3, the thioureas can be prepared by allowing II to react with an appropriate isothiocyanate (R′—N═C═S) in solvents such as tetrahydrofuran at 0-50° C. Thioamides (Ib, R″=H, alkyl_1-4) are prepared by allowing II to react with an appropriate dithioester (R′″ S—C(═S)—R″, Step 4 as illustrated in Example 4. This reaction is carried out in aqueous-alcoholic solvents at 0-50° C. in the presence of an equivalent of an alkali metal hydroxide. This reaction, especially when R′″ is methyl or ethyl, can be catalyzed by an alkali metal fluoride.

The reaction of II with R′″—S—C(S)—R′″ (R′″=CH ₃, C₂H₅) to give Ib (Step 4) can also be carried out in the presence of a tertiary amine base such as triethylamine in solvents such as THF, dioxane or methylene chloride at 10-50° C. for 3-48 hr.

When the reaction conditions are tolerated by the substituents on R (see, for example, Examples 1-3) the thioamides (Ib, R″—H, alkyl _1-4) can also be conveniently prepared (Step 5) by allowing the appropriate amide intermediates (IV) to react with reagents such as 2,4-bis(p-methoxyphenyl)-1,3-dithiadiphosphetane-2,4-disulfide (Lawesson's Reagent) in 1,4-dioxane, benzene, toluene or tetrahydrofuran at 60-110° C.; phosphorus decasulfide and sodium carbonate in tetrahydrofuran at 20-50° C. [Brillon, D., Synthetic Communications, 20, 3085 (1990)] or phosphorus decasulfide and sodium fluoride in 1,2-dimethoxyethane at 20-50° C. [Hartke, K., Gerber, H.-D., J. Prakt. Chem., 338, 763 (1996)].

Compounds Ic are prepared (Step 6) by allowing II to react first with carbon disulfide and a tertiary amine base such as triethylamine in solvent mixtures containing water and methanol, ethanol or isopropanol at 10-50° C. for 5-24 hours. The resulting intermediate is treated with an alkylating agent (R″″ X where X represents bromo, iodo, alkylsulfonyloxy or arylsulfonyloxy) at 0-30° C. to give compounds Ic. In Step 7, compounds Ic are allowed to react with alkali metal alkoxide such as sodium methoxide or potassium ethoxide in the corresponding alkanol as solvent. This reaction is conveniently carried out at the reflux temperature of the alkanol for 1-24 hr.

In order to more fully illustrate the nature of the invention and the manner of practicing the same, the following experimental examples are presented. [0689]

EXAMPLE 1

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (I)

[0690]
A stirred mixture of II (PCT/US94/08904, 3.37 g, 10.0 mmol) in dry dioxane (100 mL), under nitrogen was treated with Lawesson's Reagent (4.04 g, 10.0 mml), warmed to reflux during 1 h and refluxed for 1.5 h. The reaction was complete by TLC on silica gel with 10% MeOH—CHCl[0691] ₃. It was kept at ambient temperature for 18 h and concentrated in vacuo. Chromatography of the residue on silica gel with mixtures of acetone-methylene chloride containing 10-15% acetone gave the product which was crystallized from acetone-hexane to give 1: mp 157.5-158.5° C.; HRMS theory for C₁₆H₂₀FN₃O₃S (M⁺): 353.1209; found: 353.1212. Anal. calcd for C₁₆H₂₀FN₃O₃S: C, 54.38; H, 5.38; N, 11.89; S, 9.07. Found: C, 54.21; H, 5.58; N, 11.78; S, 8.93.

EXAMPLE 2

(S)-N-[[3-[3-Fluoro-4-[4-(5-methyl-1,3,4-thiadiazol-2-yl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (2)

[0692]
According to Example 1, for the preparation of [0693] 1, 21 (PCT/US97/01970) was allowed to react with Lawesson's Reagent in refluxing dioxane to give 2: mp 222-223° C.; HRMS theory for C₁₉H₂₄FN₆O₂S₂(M+H⁺): 451.1386; found 451.1381.

EXAMPLE 3

(S)-N-[[3-[3-Fluoro-4-[2′,5′-dioxospiro[piperidine-4,4′-imidazolidine]-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (3)

Step A: (S)-N-[[3-[3Fluoro-4-[2′,5′-dioxospiro[piperidine-4,4′-imidazolidine]-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide ([0694] 32)
A stirred suspension of [0695] 31 (WO95/25106, 0.349 g, 1.00 mmol) in 1:1 EtOH:H₂O (5 mL), under nitrogen, was treated with potassium cyanide (0.130 g, 2.00 mmol) and ammonium carbonate (0.701 g, 7.30 mmol), warmed at 65-60° C. for 5 h 15 min and kept at ambient temperature for 17 h 15 min. It was then chromatographed on silica gel with mixtures of MeOH—NH₄OH—CHCl₃containing 5-20% MeOH and 0.5% NH₄OH to give 0.280 g of 32: HRMS calcd for C₁₉H₂₂FN₅O₅: 419.1605 (M⁺); found 419.1613; Anal. calcd for C₁₉H₂₂FN₅O₅.1 H₂O: C, 52.17; H. 5.53; N. 16.01. Found: C, 52.44; H, 5.30; N, 16.11.
Step B: (S)-N-[[3-[3-Fluoro-[2′,5′-doxospiro[piperidine-4,4′-imidazolidine]-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide ([0696] 3)
A stirred suspension of [0697] 32 (0.210 g, 0.500 mmol) in dioxane (5.0 mL), under nitrogen was treated with Lawesson's Reagent (0.202 g, 0.500 mmol), refluxed for 4 h and concentrated in vacuo. The residue was chromatographed on silica gel with mixtures of MeOH—NH₄OH—CHCl₃containing 1-10% MeOH and 0.1-0.5% NH₄OH and the resulting product was crystallized from MeOH—CHCl₃EtOAc to give 0.0491 g of 3: mp 218.5° C.; HR FAB MS theory for C₁₉H₂₂FN₅O₄S (M⁺): 435.1376; found 435.1370. Anal. calcd for C₁₉H₂₂FN₅O₄S.0.5 H₂O: C, 51.34; H, 5.21; N, 15.76. Found: C, 51.69; H, 5.00; N, 15.25.

EXAMPLE 4

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (4)

[0698]
A solution of [0699] 41 (148 mg, 0.500 mmol) and 0.97 M KOH (0.515 mL) in absolute EtOH (5 mL) was added to a solution of ethyl dithioacetate (57 μL, 0.50 mmol) and sodium fluoride (20 mg, 0.47 mmol) in absolute EtOH (5 mL) and the mixture was kept at ambient temperature for 3 h 40 min. Additional ethyl dithioacetate (5 μL) was added after 1 h 55 min and additional 0.97 M KOH (40 mL) and sodium fluoride (6 mg) were added to the mixture after 3h 5 min. The reaction was followed by TLC on silica gel with 10% MeOH—CHCl₃and 30% acetone-CH₂Cl₂. The major product had an R_fon TLC that was the same as that of 4.

EXAMPLE 5

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea (5)

[0700]
A solution of [0701] 51 (PCT/US94/08904, 2.07 g, 7.00 mmol) in CH₂Cl₂was added, dropwise during 30 min, under nitrogen to an ice cold, stirred solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (1.95 g, 8.40 mmol) in CH₂Cl₂(70 mL). The mixture was warmed slowly to ambient temperature and kept for 18 h. It was then diluted with CH₂Cl₂, washed with water and aqueous NaCl, dried (Na₂SO₄) and concentrated. Chromatography of the residue on silica gel with 10% acetonitrile-CH₂Cl₂gave 1.60 g of the isothiocyanate: HRMS theory for C₁₅H₁₆FN₃O₃S (M⁺): 337.0896; found 337.0888.
Anhydrous ammonia was bubbled for 7 min through a stirred solution of the product from Step I (1.00 g, 2.96 mmol) in THF (10 mL) and the mixture was kept at ambient temperature for 3 h 25 min and concentrated in vacuo. Crystallization of the residue from acetone-hexane gave 0.861 g of [0702] 5: mp 199-199.5° C.; MS m/z 354 (M⁺). Anal. calcd for C₁₅H₁₉FN₄O₃S: C, 50.84; H, 5.40; N, 15.81. Found: C, 50.87; H, 5.39; N, 15.72.

EXAMPLE 6

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea (6)

[0703]
A stirred solution of methyl isothiocyanate (93 mg, 1.27 mmol) in THF, was treated with [0704] 61 (295 mg, 1.00 mmol), kept at ambient temperature for 18 h and concentrated in vacuo. The residue was recrystallized from EtOAc-hexane to give 246 mg of 6: mp 158-160° C.; MS m/z 368 (M⁺). Anal. calcd for C₁₆H₂₁FN₄O₃S: C, 52.16; H, 5.74; N, 15.21. Found: C, 52.20; H, 5.85; N, 15.17.

EXAMPLE 7

(S)-cis-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide

[0705]
Step 1: A mixture of (S)-(−)-N-[[3-[3-fluoro-4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide S-oxide (4.50 g, can be obtained according to the procedures disclosed in International Publication No. WO 97/09328) and platinum oxide (697 mg) in methanol (164 mL) is shaken on the Parr apparatus under a hydrogen atmosphere at 40 psi for 18 hours. The catalyst is then removed by filtration through Celite, and the filtrate is concentrated under reduced pressure and the residue chromatographed on silica gel (230-400 mesh, 350 g), eluting with a gradient of methanol/methylene chloride (3/97-7/93). Pooling and concentration of those fractions with an R[0706] _f=0.44 by TLC (methanol/chloroform, 10/90) gives (S)-cis-(−)-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide, mp 203-204° C.
Step 2: A mixture of the compound prepared in Step 1 (2.50 g) and hydroxylamine hydrochloride (2.36 g) in pyridine (30.6 mL) and ethanol (3.4 mL) is stirred in a screw-cap vial at 100° C. for 22 hrs and at ambient temperature for 16 hrs, during which additional hydroxylamine hydrochloride (944 mg) and pyridine (4 mL) is added. The reaction mixture is then concentrated under reduced pressure, diluted with saturated aqueous sodium bicarbonate (100 mL) and saline (50 mL), adjusted to pH 11 with solid sodium carbonate and extracted with methanol/methylene chloride (10/90, 5×100 mL). The combined organic phase is concentrated under reduced pressure, and the crude product is chromatographed on silica gel (230-400 mesh, 150 g), eluting with a gradient of methanol/methylene chloride (6/94-10/90). Pooling and concentration of those fractions with an R[0707] _f=0.14 by TLC (methanol/chloroform, 10/90) gives (S)-cis-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, mp 159-161° C.
Step 3: A solution of ethyl dithioacetate (105 mL, 0.919 mmol) and sodium fluoride (39 mg, 0.919 mmol) in ethanol (9.2 mL) under a nitrogen atmosphere was treated with a mixture of (S)-cis-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, as prepared in Step 2,(300 mg, 0.919 mmol) and aqueous potassium hydroxide (1M, 0.92 mL) in ethanol (46 mL). The resulting solution was stirred at ambient temperature for 4 hours and was then diluted with methylene chloride (150 mL) and washed with water (50 mL), aqueous potassium hydrogen sulfate (1M, 50 mL) and brine (25 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated in vacuo, and the crude product was triturated with methylene chloride/diethyl ether and filtered to give the title compound, mp 176-177° C. (dec.). [0708]

EXAMPLE 8

(S)-cis-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

[0709]
Step 1: A solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (235 mg, 1.01 mmol) in anhydrous methylene chloride (10 mL) at 0° C. under a nitrogen atmosphere was treated with a solution of (S-cis-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, as prepared in Example 7, Step 2, (275 mg, 0.843 mmol) in anhydrous methylene chloride (34 mL) over 30 minutes. The resulting mixture was stirred at 0° C. for 30 minutes and at ambient temperature for 1 hour and was then diluted with methylene chloride (40 mL), washed with water (25 mL) and brine (25 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was chromatographed on silica gel (70-230 mesh, 20 g), eluting with acetonitrile/methylene chloride (40/60), and those fractions with an R[0710] _f=0.07 by TLC (acetonitrile/methylene chloride, 30/70) were pooled and concentrated to give (S)-cis-3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone, mp 187-190° C. (dec.).
Step 2: A solution of (S)-cis-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone (Step 1, 290 mg, 0.787 mmol) in anhydrous tetrahydrofuran (39 mL) at 0° C. under a nitrogen atmosphere was treated (bubbled) with a stream of ammonia gas for 5 minutes. The reaction pot was sealed, and the resulting mixture was stirred at 0° C. for 1 hour. The excess ammonia was then removed under a stream of nitrogen, and the reaction mixture was concentrated in vacuo to give the crude product. Recrystallization from methanol/methylene chloride/diethyl ether gave the title compound, mp 206-208° C. (dec.). [0711]

EXAMPLE 9

(S)-trans-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide

[0712]
Step 1: (S)-(−)-N-[[3-[3-fluoro-4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5ox azolidinyl]methyl]acetamide S-oxide (disclosed in International Publication No. WO 97/09328) may be reduced to the corresponding cis and trans-sulfoxides by catalytic hydrogenation in the presence of a catalyst and solvent. Alternatively, the sulfide by product of this reduction reaction can be oxidized with an oxidizing agent such NaIO[0713] ₄or meta-chloroperoxybenzoic acid in solvent to provide the cis and trans-sulfoxides. Alternatively, the sulfide byproduct acn be oxidized selectively to the trans isomer using t-butyl hydroperoxide and a catalyst such as Ti(OiPr)4 and D-diisopropyl tartrate in a suitable solvent. The isomeric mixture can then be separated by chromatography to isolate the trans-sulfoxide, mp 211-212° C. (dec.). A mixture of the trans-sulfoxide, (S)-trans-(−)-N-[[3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide, (0.90 g) and hydroxylamine hydrochloride (0.85 g) in pyridine (11.0 mL) and ethanol (1.2 mL) is stirred in a screw-cap vial at 100° C. for 23 hrs and at ambient temperature for 19 hrs, during which additional hydroxylamine hydrochloride (340 mg) and pyridine (1 mL) is added. The reaction mixture is then concentrated under reduced pressure, diluted with saturated aqueous sodium carbonate (50 mL) and saline (50 mL) and extracted with methanol/methylene chloride (10/90, 6×100 mL). The combined organic phase is concentrated under reduced pressure, and the crude product is chromatographed on silica gel (230-400 mesh, 45 g), eluting with a gradient of methanol/methylene chloride (7.5/92.5-10/90). Pooling and concentration of those fractions with an R_f=0.14 by TLC (methanol/chloroform, 10/90) gives (S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, mp 138-140° C.
Step 2: A solution of ethyl dithioacetate (105 mL, 0.919 mmol) and sodium fluoride (39 mg, 0.919 mmol) in ethanol (9.2 mL) under a nitrogen atmosphere was treated with a mixture of (S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, as prepare in Step 1, (300 mg, 0.919 mmol) and aqueous potassium hydroxide (1M, 0.92 mL) in ethanol (46 mL). The resulting solution was stirred at ambient temperature for 17 hours and was then diluted with methylene chloride (150 mL), washed with water (2×50 mL) and brine (25 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was chromatographed on silica gel (230-400 mesh, 35 g), eluting with methanol/methylene chloride (3/97), and those fractions with an R[0714] _f=0.56 by TLC (methanol/chloroform, 10/90) were pooled and concentrated and the residue recrystallized from methylene chloride/diethyl ether to give the title compound, mp 193-194° C. (dec.).

EXAMPLE 10

(S)-trans-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

[0715]
Step 1: A solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (192 mg, 0.827 mmol) in anhydrous methylene chloride (8.3 mL) at 0° C. under a nitrogen atmosphere was treated with a solution of (S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, as prepared in Example 9, Step 1, (225 mg, 0.689 mmol) in anhydrous methylene chloride (28 mL) over 30 minutes. The resulting mixture was stirred at 0° C. for 30 minutes and at ambient temperature for 40 minutes and was then diluted with methylene chloride (20 mL), washed with water (15 mL) and brine (15 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was chromatographed on silica gel (32-63 mm, 40 g), eluting with a gradient of acetonitrile/methylene chloride (30/70-60/40) under 15 psi N[0716] ₂, and those fractions with an R_f=0.12 by TLC (acetonitrile/methylene chloride, 30/70) were pooled and concentrated to give (S)-trans-3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone, mp 165-167° C.
Step 2: A solution of (S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone (Step 1, 230 mg, 0.624 mmol) in anhydrous tetrahydrofuran (31.2 mL) at 0° C. under a nitrogen atmosphere was treated (bubbled) with a stream of ammonia gas for 5 minutes. The reaction pot was sealed, and the resulting mixture was stirred at 0° C. for 1 hour. The excess ammonia was then removed under a stream of nitrogen, and the reaction mixture was concentrated in vacuo to give the crude product. Trituration with methanol/methylene chloride/diethyl ether gave the title compound, mp 209-210° C. (dec.). [0717]

EXAMPLE 11

(S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide

[0718]
Step 1: Starting with (S)-cis-(−)-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide as prepared in Example 7, Step 1, and following the general procedure of Step 2, and making non critical variations by substituting (S)-(−)-N-[[3-[3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide S,S-dioxide (disclosed in International Publication No. WO 97/09328) for (S)-cis-(−)-N-[[3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide, the product (S)-(−)-3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone is obtained, mp 194° C. (dec.). [0719]
Step 2: A solution of ethyl dithioacetate (100 mL, 0.876 mmol) and sodium fluoride (37 mg, 0.876 mmol) in ethanol (8.8 mL) under a nitrogen atmosphere was treated with a mixture of (S)-(−)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, as prepared in Step 1, (300 mg, 0.876 mmol) and aqueous potassium hydroxide (1M, 0.88 mL) in ethanol (43.8 mL). The resulting mixture was stirred at ambient temperature for 26 hours, during which additional ethyl dithioacetate (50 mL, 0.438 mmol), sodium fluoride (19 mg, 0.438 mmol), aqueous potassium hydroxide (1M, 0.44 mL) and ethanol (3.0 mL) was added, and was then diluted with methylene chloride (150 mL), washed with water (50 mL), aqueous potassium hydrogen sulfate (1M, 50 mL) and brine (25 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was recrystallized from methylene chloride/diethyl ether to give the title compound, mp 186-187° C. (dec.). [0720]

EXAMPLE 12

(S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

[0721]
Step 1: A solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (304 mg, 1.31 mmol) in anhydrous methylene chloride (13 mL) at 0° C. under a nitrogen atmosphere was treated with a solution of (S)-(−)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, as prepared in Example 11, Step 1, (375 mg, 1.09 mmol) in anhydrous methylene chloride (88 mL) over 30 minutes. The resulting mixture was stirred at 0° C. for 30 minutes and at ambient temperature for 30 minutes and was then diluted with methylene chloride (40 mL), washed with water (25 mL) and brine (25 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was chromatographed on silica gel (230-400 mesh, 45 g), eluting with acetonitrile/methylene chloride (7.5/92.5), and those fractions with an R[0722] _f=0.64 by TLC (acetonitrile/methylene chloride, 20/80) were pooled and concentrated to give (S)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone, mp 158-162° C. (dec.).
Step 2: A solution of (S)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone (Step 1, 380 mg, 0.988 mmol) in anhydrous tetrahydrofuran (49 mL) at 0° C. under a nitrogen atmosphere was treated (bubbled) with a stream of ammonia gas for 5 minutes. The reaction pot was sealed, and the resulting mixture was stirred at 0° C. for 1 hour. The excess ammonia was then removed under a stream of nitrogen, and the reaction mixture was concentrated in vacuo to give the crude product. Recrystallization from methanol/methylene chloride/diethyl ether gave the title compound, mp 196-198° C. (dec.). [0723]

EXAMPLE 13

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-thioformamide (7)

[0724]
A stirred mixture of acetic anhydride (0.23 mL, 0.0024 mol) and 95-97% formic acid (0.10 mL, 0.0027 mL) was warmed, under nitrogen at 50-55° C. for 2 h, cooled to ambient temperature and treated, portionwise during 2 min, with [0725] 39 ⁸(0.45 g, 0.0015 mol). The suspension was kept at ambient temperature for 4 h and the resulting solution was treated with Et₂O (1 mL) and kept at ambient temperature for 18 h. The mixture was diluted with additional Et₂O (10 mL) and the solid was collected by filtration, washed with Et₂O and dried to give 0.38 g of 6 ⁹: MS (ES) m/z 324 (M+H⁺), 346 (M+Na⁺); ¹H NMR (300 mHz, CDCl₃) d 3.08 (m, 4H), 3.72 (m, 2H), 3.77 (d,d, 1H), 3.89 (m, 4H), 4.04 (t, 1H), 4.80 (m, 1H), 6.33 (s, 1H), 7.05 (m, 2H), 7.45 (d,d, 1H), 8.27 (s, 1H).
A stirred mixture of [0726] 6 (0.38 g, 0.00118 mol) in dioxane (20 mL), under nitrogen was treated with 4 (0.51 g, 0.00126 mol), warmed to reflux during 30 min and kept at this temperature for 90 min. It was then evaporated under a stream of nitrogen. The residue was chromatographed on silica gel with 1.25% MeOH—CH₂Cl₂and the slightly impure product was rechromatographed on silica gel with 25% EtOAc-CH₂Cl₂. The resulting product was crystallized from EtOAc-methyl tert-butyl ether to give 0.114 g of 7: mp 150-155° C. (dec); IR (DRIFT) 3322, 1752 cm⁻¹; MS(ES) m/z 340 (M+H⁺), 362 (M+Na⁺); ¹HNMR [300 MHz, (CD₃)₂SO] d 2.94 (m, 4H), 3.72 (m, 4H), 3.77 (d,d, 1H), 3.94 (t, 2H), 4.12 (t, 1H), 4.93 (m, 1H), 7.05 (t, 1H), 7.16 (d,d, 1H), 7.47 (d,d, 1H), 9.33 (d, 1H), 10.59 (s, 1H). Anal. calcd for C₁₅H₁₈FN₃O₃S: C, 53.08; H, 5.35; N, 12.38. Found: C, 53.02; H, 5.44; N, 12.36.

EXAMPLE 14

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiopropion-amide (9)

[0727]
An ice cold, stirred solution of [0728] 39 (0.395 g, 0.00134 mol) and triethyl amine (0.186 mL, 0.0027 mol) in CH₂Cl₂(20 mL), under nitrogen was treated, dropwise during 2 min, with a solution of propionyl chloride (0.128 mL, 0.00147 mol) in CH₂Cl₂(3 mL). The mixture was kept in the ice bath for 20 min and at ambient temperature for 1 h. It was then diluted with CH₂Cl₂, washed with saturated NaHCO₃, water and brine, dried (MgSO₄) and concentrated. The residue (8) was used without further purification in the next reaction.
A stirred mixture of the product ([0729] 8) from the previous reaction and dioxane (20 mL), under nitrogen, was treated, portionwise during 1 min, with Lawesson's reagent (0.58 g, 0.0014 mol) and refluxed for 2 h; it was then concentrated. The residue was chromatographed on silica gel with 2% MeOH—CHCl₃and the product was crystallized from methyl tert-butyl ether to give 0.259 g of 9: mp 138-139° C.; MS(ES) m/z 368 (M+H⁺), 390 (M+Na⁺); IR (DRIFT) 3284, 3266, 1748, 1744 cm⁻¹; [α]²⁴ _D+20° (MeOH); 1H NMR[300 MHz, (CD₃)₂SO] d 1.12 (t, 3H), 2.56 (q, 2H), 2.94 (m, 4H), 3.72 (m, 4H), 3.78 (d,d, 1H), 3.90 (t, 2H), 4.11 (t, 1H), 4.93 (m, 1H), 7.05 (t, 1H), 7.16 (d,d, 1H), 7.47 (d,d, 1H), 10.30 (broad s, 1H). Anal. calcd for C₁₇H₂₂FN₃O₃S: C, 55.57; H, 6.03; N, 11.44. Found: C, 55.68; H, 6.21; N, 11.37.

EXAMPLE 15

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-chlorothioacetamide (11)

[0730]
A stirred solution of [0731] 39 (1.54 g, 5.2 mmol) and triethylamine (750 mg, 7.5 mmol) in CH₂Cl₂(50 mL), under nitrogen, was treated, dropwise, during 15 min with a solution of chloroacetyl chloride (465 mL, 5.8 mmol) in CH₂Cl₂(30 mL) and kept at ambient temperature for 18 h. It was then washed with saturated NaHCO₃and dilute NaCl, dried (Na₂SO₄) and concentrated. The residue was flash chromatographed on silica gel with 20-30% acetone-CH₂Cl₂to give 1.49 g of 10 ⁹which was used in the next reaction without further purification.
A stirred mixture of [0732] 10 (0.371 g, 1.0 mmol) and Lawesson's reagent (0.420 mg, 1.04 mmol) in dioxane (10 mL) was refluxed, under nitrogen for 2 h and concentrated under reduced pressure. The residue was chromatographed on silica gel with 3-10% acetone-CH₂Cl₂to give 0.143 g of 11: MS (CI) m/z 388 (M+H⁺); ¹H NMR (300 MHz, CDCl₃) d 3.07 (m, 4H), 3.77 (d,d, 1H), 3.88 (m, 4H), 4.04 (m, 1H), 4.12 (t, 1H), 4.35 (m, 1H), 4.61 (s, 2H), 4.98 (m, 1H), 6.96 (t, 1H), 7.08 (d,d, 1H), 7.44 (d,d, 1H), 8.69 (s, 1H). Anal. calcd for C₁₆H₁₉ClFN₃O₃S: C, 49.55; H, 4.94; N, 10.83. Found: C, 49.38; H, 5.20; N, 10.27.

EXAMPLE 16

(S)-N-[[3-[3-Fluoro-4-(4-moropholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α,α-trifluorothioacetamide (13)

[0733]
An ice cold stirred solution of [0734] 39 (0.590 g, 2.0 mmol) and triethylamine (640 mL, 4.6 mmol) in CH₂Cl₂(10 mL) was treated with trifluoroacetic anhydride (325 mL, 2.3 mmol) and kept in the ice bath for 10 min and then at ambient temperature. The reaction was followed by TLC on silica gel with 30% acetone-CH₂Cl₂. Additional trifluoroacetic anhydride and triethylamine were added after 3 d (64 mL/125 mL), 4 d (100 mL/220 mL) and 6 d (325 mL/1.0 mL). The reaction was complete 1 h after the last addition; it was mixed with CH₂Cl₂, washed with water and dilute NaCl, dried (Na₂SO₄) and concentrated. The solid residue was recrystallized from acetone-heptane to give 0.566 g of 12: mp 161-164° C. (dec); MS(EI) m/z 391 (M⁺). Anal. calcd for C₁₆H₁₇F₄N₃O₄: C, 49.11; H, 4.38; N, 10.74. Found: C, 48.99; H, 4.56; N, 10.73.
A stirred mixture of [0735] 12 (0.391 g, 1.0 mmol) and Lawesson's reagent (0.422 g, 1.1 mmol) in dioxane (10 mL) was refluxed, under nitrogen for 2 h, cooled slowly to ambient temperature and concentrated in vacuo. The residue was flash chromatographed on silica gel with 5-15% acetone-CH₂Cl₂and the product was crystallized from acetone-heptane to give 0.249 g of 13: mp 151-152° C.; MS(EI) m/z 407 (M⁺), 363, 209, 151, 95; ¹H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.75 (d,d, 1H), 3.87 (m, 4H), 3.95 (m, 1H), 4.14 (t, 1H), 4.32 (m, 1H), 5.01 (m, 1H), 6.92 (t, 1H), 7.05 (d,d, 1H), 7.38 (d,d, 1H), 9.03 (s, 1H). Anal. calcd for C₁₆H₁₇F₄N₃O₃S: C, 47.17; H, 4.21; N, 10.31. Found: C, 47.09; H, 4.35; N, 10.27.

EXAMPLE 17

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-fluorothioacetamide (15)

[0736]
A stirred, ice cold solution of [0737] 39 (0.590 g, 2.0 mmol) and triethylamine (611 mL, 4.4 mmol) in CH₂Cl₂(10 mL), under nitrogen, was treated, dropwise, with a solution of fluoroacetyl chloride (220 mL, 2.2 mmol) in CH₂Cl₂(5 mL), kept in the ice bath for 10 min and at ambient temperature for 2 h. It was then diluted with CH₂Cl₂, washed with water and dilute NaCl, dried (Na₂SO₄) and concentrated. The residue was chromatographed on silica gel with 10-30% acetone-CH₂Cl₂to give 0.180 g of 14: MS(ES) m/z 356 (M+H⁺), 378 (M+Na⁺).
A solution of [0738] 14 (0.180 g, 0.507 mmol) in dioxane, under nitrogen, was treated with Lawesson's reagent (0.206 g, 0.51 mmol), warmed at 90-100° C. for 1 h and concentrated in vacuo. The residue was chromatographed on silica gel with 15% acetone-CH₂Cl₂to give 0.161 g of 15: MS(EI) m/z 371 (M⁺); ¹H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.78 (d,d, 1H), 3.87 (m, 4H), 4.03 (m, 1H), 4.11 (t, 1H), 4.38 (m, 1H), 4.98 (m, 1H), 5.07 (s, 1H), 5.23 (s, 1H), 6.93 (t, 1H), 7.08 (dd, 1H), 7.42 (d,d, 1H), 8.42 (s, 1H). Anal. calcd for C₁₆H₁₉F₂N₃O₃S: C, 51.74; H, 5.16; N, 11.31. Found: C, 51.79; H, 5.31; N, 11.02.

EXAMPLE 18

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α-difluorothioacetamide (17)

[0739]
A stirred, ice cold mixture of [0740] 39 (0.590 g, 2.0 mmol), difluroacetic acid (190 mL, 2.0 mmol), and 1-hydroxybenzotriazole (0.297 g, 2.2 mmol) in DMF (5 mL) under nitrogen, was treated with 1-(3-diethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.843 g, 4.4 mmol) and kept at ambient temperature for 18 h. It was diluted with CH₂Cl₂, washed with water and dilute NaCl, dried (Na₂SO₄) and concentrated. The solid residue was crystallized form EtOAc-heptane to give 0.617 g of 16: mp 149-150° C.; 1H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.66 (m, 2H), 3.85 (m, 5H), 4.08 (t, 1H), 4.80 (m, 1H), 5.93 (t, J=53.9 Hz, 1H), 6.92 (t, 1H), 7.06 (m, 2H), 7.39 (d,d, 1H); MS(EI) m/z 373 (M⁺). Anal. calcd for C₁₆H₁₈F₃N₃O₄: C, 51.48; H, 4.86; N, 11.26. Found: C, 51.59; H, 4.91; N, 11.29.
A stirred solution of [0741] 16 (0.373 g, 1.00 mmol) in dioxane (10 mL), under nitrogen was treated with Lawesson's reagent (0.404 g, 1.00 mmol), warmed at about 95° C. for 1 h and concentrated in vacuo. Chromatography of the residue on silica gel with 10% acetone-CH₂Cl₂and cyrstallization of the product from EtOAc-heptane gave 0.276 g of 17: mp 125-127° C.; MS(EI) m/z 389 (M⁺), 345, 305, 247, 209, 195, 151, 138, 123, 109, 95; ¹H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.76 (d,d, 1H), 3.86 (m, 4H), 4.01 (m, 1H), 4.12 (t, 1H), 4.30 (m, 1H), 4.99 (m, 1H), 6.20 (t, J=55.9 Hz, 1H), 6.92 (t, 1H), 7.06 (d,d, 1H), 7.38 (d,d, 1H), 8.78 (broad s, 1H). Anal. calcd for C₁₆H₁₈F₃N₃O₃S: C, 49.35; H, 4.66; N, 10.79. Found: C, 49.37; H, 4.71; N, 10.83.

EXAMPLE 19

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-cyanothioacetamide (19)

[0742]
An ice cold, stirred mixture of [0743] 39 (0.646 g, 2.19 mmol), cyanoacetic acid (0.179 g, 2.1 mmol) and 1-hydroxybenzotriazole (0.351 g, 2.6 mmol) in DMF (5 mL), under nitrogen, was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.997 g, 5.2 mmol) and kept at ambient temperature for 24 h. It was diluted with CH₂Cl₂, washed with water and dilute NaCl, dried (Na₂SO₄) and concentrated. The solid residue was crystallized from EtOAc-heptane to give 0.546 g of 18: mp 172-174° C.: IR (DRIFT) 3316, 2256, 1754, 1684 cm⁻¹; MS(EI) m/z 362 (M⁺). Anal. calcd for C₁₇H₁₉FN₄O₄: C, 56.35; H, 5.28; N, 15.46. Found: C, 56.33; H, 5.30; N, 15.36.
A stirred solution of [0744] 18 (0.453 mg, 1.25 mmol) in dioxane (10 mL), under nitrogen, was treated with Lawesson's reagent (0.505 g, 1.25 mmol) and warmed at about 100° C. When the reaction was over (TLC with 30% acetone-CH₂Cl₂) the mixture was cooled and concentrated in vacuo. Chromatography of the residue on silica gel with 10-20% acetone-CH₂Cl₂and crystallization of the product from EtOAc-heptane gave 0.110 g of 19: mp 186-187° C. (dec); MS(ES) m/z 379 (M+H⁺), 401 (M+Na⁺); ¹H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.81 (d,d, 1H), 3.86 (m, 4H), 3.89 (s, 2H), 4.09 (t, 1H), 4.14 (m, 2H), 5.01 (m, 1H), 6.92 (t, 1H), 7.05 (d,d, 1H), 7.34 (d,d, 1H), 9.15 (s, 1H); IR (DRIFT) 3244, 2260, 1754 cm⁻¹. Anal. calcd for C₁₇H₁₉FN₄O₃S: C, 53.96; H, 5.06; N, 14.81. Found: C, 53.88; H, 5.39; N, 14.61.

EXAMPLE 20

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]α,α-dichlorothioacetamide (21)

[0745]
A stirred, ice cold solution of [0746] 39 (0.885 g, 3.00 mmol) and triethylamine (975 mL, 7 mmol) in CH₂Cl₂(15 mL), under nitrogen was treated, dropwise with a solution of dichloroacetic anhydride (555 mL, 3.5 mmol) in CH₂Cl₂(5 mL) and kept in the ice bath for 15 min and at ambient temperature for 18 h. It was diluted with CH₂Cl₂, washed with water, saturated NaHCO₃and dilute NaCl, dried (Na₂O₄) and concentrated. Chromatography of the residue on silica gel with 10% acetone-CH₂Cl₂and crystallization of the product from acetone-heptane gave 0.463 g of 20: mp 197-198° C. (dec); MS(ES) m/z 406 (M+H⁺), 428 (M+Na⁺); ¹H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.75 (m, 3H), 3.86 (m, 4H), 4.07 (t, 1H), 4.83 (m, 1H), 5.94 (s, 1H), 6.92 (t, 1H), 7.06 (m, 2H), 7.41 (d,d, 1H).
A stirred solution of [0747] 20 (0.306 g, 0.75 mmol) in dioxane (5 ml), under nitrogen, was treated with Lawesson's reagent (0.202 g, 0.5 mmol), warmed at about 90° C. for 1 hour, cooled and concentrated in vacuo. Chromatography of the residue on silica gel first with 30% acetone-heptane and then with 10% acetone-methylene chloride and crystallization of rh product form methylene chloride-heptane gave 0.203 g with 21: mp 143-144° cd.; HR17S (EI) calculated for C₁₆H₁₈cl₂F N₃O₃S(M) 421.0431. Anal. calcd for C₁₆H₁₈cl₂F N₃O₃S, C, 45.51; H, 4.30; N, 9.95. Found: C, 45.47; H, 4.24; H, 9.88.

EXAMPLE 21

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-(methoxycarbonyl)thioacetamide (23)

[0748]
A stirred solution of [0749] 39 (0.955 g, 3.2 mmol) and triethylamine (650 mL, 4.5 mmol) in CH₂Cl₂(50 mL), under nitrogen, was treated, dropwise during 15-20 min with a solution of methyl malonyl chloride (475 mL, 4.3 mmol) in CH₂Cl₂(10 mL) and kept at ambient temperature for 3 days. It was then washed with water and dilute NaCl, dried and concentrated. The residue was flash chromatographed on silica gel with 15-30% acetone-CH₂Cl₂and the product was crystallized form acetone-hexane to give 0.873 g of 22: mp 150-151° C.; ¹H NMR (300 MHz, CDCl₃) d 3.03 (m, 4H), 3.34 (s, 2H), 3.67 (s, 3H), 3.69 (m, 2H), 3.76 (d,d, 1H), 3.85 (m, 4H), 4.00 (t, 1H), 4.78 (m, 1H), 6.90 (t, 1H), 7.06 (d,d, 1H), 7.41 (d,d, 1H), 7.57 (t, 1H); MS(ES) m/z 396 (M+H⁺), 418 (M+Na⁺); HRMS (FAB) calcd for C₁₈H, FN₃O₆(M+H⁺) 396.1571, found 396.1579. Anal. calcd for C₁₈H₂₂FN₃O₆: C, 54.68; H, 5.61; N, 10.63. Found: C, 54.69; H, 5.68; N, 10.58.
A stirred solution of [0750] 22 (0.395 g, 1.0 mmol) in dioxane (10 mL), under nitrogen, was treated with Lawesson's reagent (0.202 g, 0.5 mmol) and kept at ambient temperature for 4 h 10 min and at 80-90° C. for 1.5 h. The reaction was followed by TLC on silica gel with 10% MeOH—CHCl₃. At this time a new, less polar product had begun to form. It was kept at ambient temperature for 18 h and at 80° C. for 2 h; additional Laewsson's reagent (40 mg, 0.099 mmol) was added and warming at 80° C. was continued for 2 h; some starting material still remained. The mixture was concentrated and the residue was chromatographed on silica gel with 15% acetone-CH₂Cl₂to give 0.348 g of 23: ¹H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.71 (s, 3H), 3.81 (d,d, 1H), 3.86 (m, 4H), 3.88 (s, 2H), 4.07 (t, 1H), 4.19 (m, 2H), 4.99 (m, 1H), 6.91 (t, 1H), 7.07 (d,d, 1H), 7.42 (d,d, 1H), 9.52 (s, 1H); IR (DRIFT) 3269, 1743 cm⁻¹; MS(EI) m/z 411 (M⁺). Anal. calcd for C₁₈H₂₂FN₃O₅S: C, 52.54; H, 5.39; N, 10.21. Found: C, 52.58; H, 5.43; N, 10.14.

EXAMPLE 22

(S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (25)

[0751]
A stirred mixture of [0752] 24 (0.150 g, 0.470 mmol) and dioxane (12.5 mL), under nitrogen, was treated with Lawesson's reagent (0.20 g, 0.50 mmol), refluxed for 1.5 h, kept at ambient temperature for 18 h and concentrated in vacuo. Flash chromatography of the residue on silica gel with 5% MeOH—CHCl₃gave the product which was crystallized from MeOH to give 0.100 g (63.4%) of 25: mp 161-163° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.43 (s, 3H), 3.87 (m, 3H), 4.22 (t, 1H), 4.99 (m, 1H), 7.51 (d, 1H), 7.77 (m, 2H), 8.26 (s, 1H), 8.97 (d, 1H), 10.35 (broad s, 1H); IR (mull) 3259, 3226, 3044, 1752 cm⁻¹; MS(ES) m/z 336 (M+H⁺), 358 (M+Na⁺). Anal. calcd for C₁₄H₁₄FN₅O₂S: C, 50.14; H, 4.21; N, 20.88. Found: C, 50.18; H, 4.26; N, 20.94.

EXAMPLE 23

[0753]
A stirred mixture of [0754] 26 (0.26 g, 0.938 mmol), ethyl dithioacetate (0.12 g, 0.998 mmol), sodium fluoride (0.040 g, 0.953 mmol) and absolute EtOH (10 mL), under nitrogen, was treated during 5 min with a solution of 0.97 M KOH (1.03 mL) in EtOH and kept at ambient temperature for 2 h. It was then diluted with CH₂CL₂(75 mL), washed with water, 1M KHSO₄, water and brine and evaporated. The residue was flash chromatographed on silica gel with 5% MeOH—CHCl₃and the product was crystallized from MeOH to give 0.118 g, mp 164-165° C. (dec) and 0.026 g, mp 162-163° C. (dec) of 25.

EXAMPLE 24

(S)-N-[[3-[1-(Hydroxyacetyl)-5-indolinyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (28)

[0755]
A stirred, ice cold solution of [0756] 52 (8.80 g, 0.0240 mol) in CH₂Cl₂(25 mL) was treated during 20 min with a solution of trifluoroacetic acid (25 mL) in CH₂Cl₂(10 mL). The mixture was kept in the ice bath for 2 h 15 min and concentrated under reduced pressure. A solution of the residue in CH₂Cl₂was washed with saturated NaHCO₃and dilute NaCl, dried (Na₂SO₄) and concentrated. The residue was used in the next reaction without further purification. A sample of this material (53) had: ¹H NMR (300 MHz, CDCl₃) d 3.00 (t, 2H), 3.54 (t, 2H), 3.85 (broad s, 1H), 5.17 (s, 2H), 6.59 (d, 1H), 6.66 (broad s, 1H), 6.91 (d, 1H), 7.23 (s, 1H), 7.36 (m, 5H); MS m/z 269 (M+H⁺).
An ice cold, stirred mixture of [0757] 53 (crude product from the previous reaction), acetone (200 mL), saturated NaHCO₃(200 mL) and water (30 mL) was treated, dropwise during 20 min, with a solution of benzyloxyacetyl chloride (4.70 mL, 0.030 mol) in acetone (55 mL), warmed slowly to ambient temperature and kept for 18 h. Additional benzyloxytacetyl chloride (1.0 mL) in acetone 35 mL) was added dropwise and the mixture was kept at ambient temperature for an additional 3 h and diluted with EtOAc and water. A solid was collected by filtration and dried to give 4.00 g of crude product. The EtOAc solution was dried (Na₂SO₄) and concentrated to give 5.36 g of additional crude product. Crystallization of the product from EtOAc gave a total of 6.35 g of 54 ¹⁴, mp 157-159.5° C. The analytical sample had: mp 158-159.5° C.; ¹H NMR (300 MHz, CDCl₃) δ 3,16 (t,2H), 4.01(t,2H), 4.21 (s, 2H), 4.69 (s, 2H), 5.19 (s, 2H), 6.67 (s, 1H), 6.97 (d, 1H), 7.36 (m, 10H), 7.50 (braod s, 1H), 8.15 (d, 1H); MS(EI) m/z (relative intensity) 416 (M⁺, 9), 310 (8), 202 (10), 133 (8), 92 (8), 91 (99), 79 (7), 77 (9), 65 (12), 51 (6); IR (mull) 2381, 1722, 1659, 1608, 1558 cm⁻¹. Anal. calcd for C₂₅H₂₄N₂O₄: C, 72.10; H, 5.81; N, 6.73. Found: C, 72.05; H, 5.86; N, 6.68.
A stirred suspension of [0758] 54 (1.16 g, 2.78 mmol) in THF (42 mL) was cooled, under nitrogen, to 78° C. and treated, dropwise, during 5 min with 1.6 M n-BuLi in hexane (1.83 mL). It was kept at 78° C. for 50 min, treated, dropwise, during 5 min with a solution of (R)-(−)-glycidyl butyrate (0.500 g, 3.47 mmol) in THF (2 mL), allowed to warm to ambient temperature during 3 h and kpet for 18 h. It was then diluted with EtOAc, washed with saturated NH₄Cl, water and brine, dried (MgSO₄) and concentrated. Chromatography of the residue on silica gel with 3% MeOH—0.2% NH₄OH—CHCl₃gave 0.60 g (56%) of 55¹⁴: ¹H NMR [300 MHz, (CD₃)₂SO] δ 3.14 (t, 2H), 3.59 (m, 2H), 3.79 (d,d, 1H), 4.03 (m, 3H), 4.29 (s, 2H), 4.58 (s, 2H), 4.65 (m, 1H), 5.20 (t, 1H), 7.31 (m, 6H), 7.55 (s, 1H), 8.03 (d, 1H); MS(ES) m/z 383 (M+H⁺), 405 (M+Na⁺).
An ice cold, stirred mixture of [0759] 55 (0.60 g, 1.57 mmol), triethylamine (2.2 mL), and CH₂Cl₂(12 mL), under nitrogen, was treated with 3-nitrobenzenesulfonyl chloride (0.44 g, 1.99 mmol) and kept in the ice bath for 30 min and at ambient temperature for 60 min. It was then diluted with CH₂Cl₂, washed with water and brine, dried (Na₂SO₄) and concentrated. Chromatography of the residue on silica gel with 15% CH₃CN—CH₂Cl₂gave 0.70 g of 56: ¹H NMR (300 MHz, CDCl₃) d 3.19 (t, J=8.3 Hz, 2H), 3.88 (d,d, 1H), 4.04 (t, J=8.4 Hz, 2H), 4.14 (t, 1H), 4.23 (s, 2H), 4.42 (m, 2H), 4.70 (s, 2H), 4.84 (m, 1H), 6.97 (m, 1H), 7.34 (m, 5H), 7.58 (s, 1H), 7.81 (t, 1H), 8.22 (m, 2H), 8.53 (m, 1H), 8.73 (m, 1H); MS(ES) m/z 568 (M+H⁺), 590 (M+Na⁺).
A stirred mixture of [0760] 56 (crude product from 0.00314 mol of 55), acetonitride (70 mL), isopropanol (70 mL) and 29% ammonium hydroxide (70 mL) was warmed at 40-44° C. for 7h and kept at ambient temperature for 18 h. It was concentrated in vacuo to an aqueous residue with was extracted with CH₂Cl₂. The extract was washed with water and brine, dried (Na₂SO₄) and concentrated. Chromatography of the residue on silica gel with 8% MeOH0.5% NH₄OH—CHCl₃gave 1.05 g of 57: ¹H NMR [300 MHz, (CD₃)₂SO] d 2.78 (m, 2H), 3.13 (t, 2H), 3.82 (d,d, 1H), 4.01 (m, 3H), 4.29 (s, 2H), 4.58 (s, 2H), 4.58 (m, 1H), 7.31 (m, 6H), 7.54 (broad s, 1H), 8.03 (d, 1H); MS(ES) m/z 382 (M+H⁺), 404 (M+Na⁺).
A mixture of [0761] 57 (0.46 g, 1.21 mmol), MeOH (150 mL), 1 M HCl (1.2 mL) and 5% palladium-on-carbon catalyst (250 mg) was hydrogenated at an initial pressure of 49 psi for 5 h. Additional 1M HCl (0.5 mL) and catalyst (100 mg) were added and hydrogenation was continued for 18 h. The catalyst was removed by filtration and the filtrate was concentrated to give 0.34 g of 27: ¹H NMR [300 MHz, (CD₃)₂SO] δ 3.15 (t, 2H), 3.22 (broad s, 2H), 3.84 (d,d, 1H), 4.00 (t, 2H), 4.15 (s, 2H), 4.15 (m, 1H), 4.92 (m, 1H), 7.24 (q, 1H), 7.50 (d, 1H), 8.03 (d, 1H), 8.37 (broad s, 3H); MS(ES) m/z 2.92 (M+H⁺).
A suspension of [0762] 27 (0.10 g, 0.34 mmol) in a mixture of EtOH (15 mL) and 0.97 M KOH (0.7 mL) was added, under nitrogen to a stirred mixture of ethyl dithioacetate (0.0412 g, 0.343 mmol) and sodium fluoride (0.0137 g, 0.326 mmol) in EtOH (5 mL) and the mixture was kept at ambient temperature for 2h 15 min. Additional 0.97 M KOH (0.2 mL), sodium iodide (6 mg) and ethyl dithioacetate (20 mg) were added and the mixture was stirred for 2 h, mixed with CH₂Cl₂(150 mL), washed with water, 1M KHSO₄and brine, dried (Na₂SO₄) and concentrated. The residue was crystallized from acetone to give 0.0404 g of 28: mp 175-176° C. (dec); MS (FAB) m/z 350 (M+H⁺), 349 (M⁺), 331, 316, 205, 73; HR MS (FAB) calcd for C₁₆H₂₀N₃O₄S (M+H⁺) 350.1174, found 350.1183; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.42 (s, 3H), 3.14 (t, 2H), 3.79 (d,d, 1H), 3.89 (t, 2H), 4.00 (t, 2H), 4.12 (m, 3H), 4.83 (t, 1H), 4.90 (m, 1H), 7.25 (d, 1H), 7.50 (s, 1H), 8.03 (d, 1H), 10.35 (s, 1H); IR (DRIFT) 3255, 3223, 3068, 1747, 1639, 1614 cm⁻¹.
EXAMPLE 25: (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide ([0763] 30)
A mixture of [0764] 58 (3.00 g, 7.00 mmol), THF (60 mL), absolute EtOH (100 mL) and 10% palladium-on-carbon catalyst (415 mg) was hydrogenated at an initial pressure of 58 psi for 2 h 50 min. The catalyst was removed by filtration and the filtrate was concentrated in vacuo to give 2.67 g of 59 which was used without further purification in the next reaction: ¹H NMR (300 MHz, CDCl₃) d 2.16 (broad s), 3.02 (m, 8H), 3.73 (d,d, J=3.9, 12.6 Hz, 1H), 3.96 (m, 3H), 4.72 (m, 1H), 6.92 (t, J=9.2 Hz, 1H), 7.11 (m, 1H), 7.43 (d,d, J=2.6, 14.3 Hz, 1H); MS(ES) m/z 296 (M+H⁺).
A stirred, ice cold mixture of [0765] 59 (2.67 g from the previous reaction), acetone (190 mL) and saturated NaHCO₃(70 mL) was treated, dropwise during 2-3 min with a solution of benzyloxyacetyl chloride (1.34 mL, 8.61 mmol) in acetone (25 mL), kept in the ice bath for 1 h and diluted with EtOAc. The aqueous layer was extracted with EtOAc and the combined organic solution was washed with dilute NaCl, dried and concentrated. Chromatography of the residue on silica gel with 30% acetone-CH₂Cl₂gave 2.64 g of 60: ¹H NMR (300 MHz, CDCl₃) d 2.28 (broad s, 1H), 3.00 (m, 4H), 3.66 (m, 2H), 3.77 (m, 3H), 3.96 (m, 3H), 4.22 (s, 2H), 4.61 (s, 2H), 4.74 (m, 1H), 6.88 (t, J=9.2 Hz, 1H), 7.12 (m, 1H), 7.35 (s, 5H), 7.46 (d,d, J=2.6, 14.2 Hz, 1H); IR (mull) 3406, 1748, 1647 cm⁻¹; HRMS(EI) calcd for C₂₃H₂₆FN₃O₅(M⁺) 443.1856, found 443.1842.
A stirred, ice cold mixture of [0766] 60 (2.64 g, 6.00 mmol) and triethylamine (1.14 mL, 8.16 mmol) in CH₂Cl₂(200 mL), under nitrogen, was treated with 3-nitrobenzenesulfonyl chloride (1.78 g, 8.04 mmol), warmed to ambient temperature and kept for 5 h 20 min. Additional 3-nitrobenzenesulfonyl chlroide (180 mg) and triethylamine (0.20 mL) were added and the mixture was kept at ambient temperature for 18 h, diluted with CH₂Cl₂and washed with water and dilute NaCl, dried (Na₂SO₄) and concentrated. Chromatography of the residue on silica gel with 40-60% acetone-hexane gave 3.36 g of 77: ¹H NMR (300 MHz, CDCl₃) d 3.02 (broad s, 4H), 3.66 (broad s, 2H), 3.78 (broad s, 2H), 3.87 (d,d, J=5.9, 9.1 Hz, 1H), 4.09 (t, J=9.2 Hz, 1H), 4.22 (s, 2H), 4.41 (m, 2H), 4.61 (s, 2H), 4.84 (m, 1H), 6.88 (t, J=9.1 Hz, 1H), 7.02 (m, 1H), 7.35 (m, 6H), 7.82 (t, J=8.0 Hz, 1H), 8.23 (m, 1H), 8.53 (m, 1H), 8.73 (m, 1H); MS(ES) m/z 629 (M+H⁺).
A solution of [0767] 77 (3.36 g, 5.34 mmol) in a mixture of acetonitrile (90 mL), isopropanol (90 mL) and concentrated ammonium hydroxide (90 mL) was warmed at 40-45° C., for 18 h, treated with additional ammonium hydroxide (30 mL), warmed at 40-45° C. for 8 h, treated with additional ammonium hydroxide (25 mL) and warmed at 45° C. for 18 h. It was then mixed with water and extracted with CH₂Cl₂. The extract was washed with dilute NaCl, dried (Na₂SO₄) and concentrated. Chromatography of the residue on silica gel with 5% MeOH-0.5% NH₄OH—CHCl₃gave 2.44 g of 61: ¹H NMR (300 MHz, CDCl₃) d 1.50 (broad s), 3.04 (m, 6H), 3.65 (broad s, 2H), 3.81 (m, 3H), 3.99 (t, 1H), 4.21 (s, 2H), 4.61 (s, 2H), 4.66 (m, 1H), 6.88 (t, 1H), 7.12 (m, 1H), 7.33 (m, 5H), 7.47 (d,d, 1H); MS(ES) m/z 443 (M+H⁺).
A solution of [0768] 61 (1.45 g, 3.3 mmol) and 1.0 N HCl (3.65 mL) in 95% EtOH (150 mL) was treated with 5% palladium-on-carbon catalyst (500 mg) and hydrogenated at an initial pressure of 54 psi for 20 h 15 min. Additional 1.0 N HCl (0.5 mL) and catalyst (100 mg) were added and hydrogenation was continued for 20 h 30 min at an initial pressure of 60 psi. The reaction was compete by TLC; it was neutralized with concentrated NH₄OH, filtered and concentrated in vacuo to give 1.18 g of 29: ¹H NMR [300 MHz, (CD₃)₂SO] d 2.94 (broad s, 4H), 3.19 (m, 2H), 3.48 (broad s, 2H), 3.60 (broad s, 2H), 3.84 (m, 1H), 4.14 (m, 3H), 4.66 (broad s, 1H), 4.93 (m, 1H), 7.07 (t, 1H), 7.16 (d,d, 1H), 7.48 (d,d, 1H), 8.04 (broad s); IR (mull) 3420, 3099, 3040, 3008, 1755, 1641 cm⁻¹; MS(ES) m/z 353 (M+H⁺). Anal. calcd for C₁₆H₂₂ClFN₄O₄: C, 49.42; H, 5.70; Cl, 9.12; N, 14.41. Found: C, 48.16; H, 5.82; Cl, 10.00; N, 14.28.
A stirred mixture of ethyl dithioacetate (180 mL, 1.56 mmol), sodium fluoride (72 mg, 1.7 mmol), 29 (500 mg, 1.29 mmol) and EtOH (70 mL) under nitrogen, was treated with 0.97M KOH (1.46 mL, 1.42 mmol) and the resulting solution was kept at ambient temperature for 3 h 35 min, diluted with CHCl[0769] ₃, washed with water and dilute NaCl, dried (Na₂SO₄) and concentrated. Chromatography of the residue on silica gel with 5% MeOH-0.5% NH₄OH—CHCl₃and crystallization of the resulting product from absolute EtOH gave 0.238 mg (44.9%) 30: mp 163-165° C.; ¹H NMR (300 MHz, CDCl₃) d 2.60 (s, 3H), 3.06 (m, 4H), 3.45 (m, 2H), 3.61 (m, 1H), 3.82 (m, 3H), 4.07 (m, 2H), 4.25 (m, 3H), 4.97 (m, 1H), 6.91 (t, 1H), 7.07 (m, 1H), 7.45 (d,d, 1H), 7.91 (broad s, 1H); MS(FAB) m/z (relative intensity) 411 (M+H+, 100), 410 (M⁺, 66.5), 266 (3.1); IR 3292, 1733, 1653 cm⁻¹. Anal. calcd for C₁₈H₂₃FN₄O₄S: C, 52.67; H, 5.65; N, 13.65. Found: C, 52.76; H, 5.58; N, 13.64.

EXAMPLE 26

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (32)

[0770]
An ice cold, stirred mixture of [0771] 31 (0.38 g, 0.0012 mol) and triethylamine (0.38 mL, 0.0027 mol) in THF (12 mL), under nitrogen, was treated with ethyl dithioacetate (0.16 mL, 0.0014 mol) and then kept at ambient temperature for 24.5 h and concentrated in vacuo. A solution of the residue in CH₂Cl₂was washed with saturated NaHCO₃, water and brine, dried (MgSO₄) and concentrated. Crystallization of the residue from EtOAc-hexane gave 0.355 g of 32: mp 155-156° C.; MS(ES) m/z 370 (M+H⁺), 392 (M+Na⁺); IR (DRIFT) 3206, 3042, 1759, 1738 cm⁻¹; ¹H NMR (300 MHz, CDCl₃) d 2.60 (s, 3H), 2.95 (s, 4H), 3.43 (m, 4H), 3.82 (d, d, 1H), 4.08 (m, 2H), 4.27 (m, 1H), 4.98 (m, 1H), 7.06 (m, 1H), 7.33 (broad s, 1H), 7.51 (d, 1H), 8.03 (broad s, 1H). Anal. calcd for C₁₆H₂₀FN₃O₂S₂: C, 52.01; H, 5.46; N, 11.37. Found: C, 51.86; H, 5.43; N, 11.20.

EXAMPLE 27

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio-acetamide, thiomorpholine S-oxide (34)

[0772]
An ice cold, stirred mixture of sodium metaperiodate (1.08 g, 5.05 mmol) and water (12 mL), under nitrogen, was treated with [0773] 62 (1.5 g, 4.8 mmol) and MeOH (17 mL) and kept at 6° C. for 18 h and at 4° C. for 3 h. It was then treated with additional sodium metaperiodate (0.1 g), kept at 4° C. for 3 h and extracted with CHCl₃. The extract was dried (MgSO₄) and concntrated to give 1.4 g of 63: ¹H NMR [300 MHz, (CD₃)₂SO] d 2.84 (m, 2H), 3.01 (m, 2H), 3.16 (m, 2H), 3.50 (m, 3H), 3.65 (m, 1H), 3.77 (d,d, 1H), 4.03 (t, 1H), 4.66 (m, 1H), 5.18 (t, 1H), 7.16 (m, 2H), 7.52 (m, 1H); MS(ES) m/z 329 (M+H⁺), 351 (M+Na⁺).
An ice cold, stirred mixture of [0774] 63 (1.27 g, 3.87 mmol) and triethylamine (0.732 mL, 5.25 mmol) in CH₂Cl₂(130 mL), under nitrogen, was treated with m nitrobenzenesulfonyl chloride (1.15 g, 5.19 mmol) and kept at ambient temperature for about 24 h. It was diluted with CH₂Cl₂, washed with water and brine, dried (Na₂SO₄) and concentrated to give 78 which was used in the next reaction without purification.
A stirred mixture of the product ([0775] 78) from the previous reaction, acetonitrile (70 mL) and isopropanol (70 mL) was treated with concentrated ammonium hydroxide (70 mL, 29.9% NH₃) and kept at 40° C. for 2 h, at ambient temperature for 18 h and at 40-45° C. for 4 h; it was concentrated to about 50 mL, diluted with water and extracted with CH₂Cl₂. The extracts were washed with water and brine, dried (MgSO₄) and concentrated. Chromatography of the residue on silica gel with 5% MeOH—CHCl₃gave 0.58 g of 33: MS(ES) m/z 328 (M+H⁺), 350 (M+Na); ¹H NMR [300 MHz, (CD₃)₂SO] d 2.81 (m, 4H), 3.01 (m, 2H), 3.16 (m, 2H), 3.30 (broad s), 3.49 (m, 2H), 3.80 (d,d, 1H), 4.01 (t, 1H), 4.58 (m, 1H), 7.19 (m, 2H), 7.51 (m, 1H).
A stirred suspension of [0776] 33 (3.7 g, 0.011 mol) and triethylamine (3.5 mL, 0.025 mol) in THF (120 mL) was cooled, in an ice bath, under nitrogen, treated, dropwise during 2 min, with a solution of ethyl dithioacetate (1.47 mL, 0.0128 mol) in THF (2 mL) and kept at ambient temperature for 22 h. The resulting solution was concentrated and the residue crystallized from acetonitrile to give 3.61 g of 34: mp 176-177° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.42 (s, 3H), 2.85 (m, 2H), 3.01 (m, 2H), 3.18 (m, 3H), 3.50 (m, 2H), 3.78 (d,d, 1H), 3.89 (broad s, 2H), 4.12 (t, 1H), 4.92 (m, 1H), 7.18 (m, 2H), 7.49 (m, 1H), 10.33 (s, 1H); IR (DRIFT) 3186, 3102, 1741 cm⁻¹; MS(ES) m/z 386 (M+H⁺), 408 (M+Na⁺). Anal. calcd for C₁₆H₂₀FN₃O₃S₂∘0.05 H₂O: C, 48.71; H, 5.37; N, 10.65; S, 16.26; H₂O, 2.38. Found: C, 48.75; H, 5.17; N, 10.72; S, 16.07; H₂O, 1.72.

EXAMPLE 28

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiomorpholine S, S-dioxide (36)

[0777]
A stirred mixture of [0778] 62 (0.399 g, 0.00128 mol) in 25% water/acetone (12 mL), under nitrogen was treated with N-methylmorpholine, N-oxide (0.45 g, 0.00384 mol) and 0.1 mL of a 2.5 wt % solution of osmium tetroxide in tert-butanol. It was kept at ambient temperature for 18 h, mixed with saturated NaHSO₃(50 mL) and extracted with CH₂Cl₂. The extract was washed with saturated NaHSO₃and brine, dried (Na₂SO₄) and concentrated. The residue was mixed with 3.5% MeOH—CH₂Cl₂and filtered; the solid was dissolved in 15% MeOH—CH₂Cl₂and concentrated to give 0.29 g of 64. The filtrate was chromatographed on silica gel with 3.5% MeOH—CH₂Cl₂to give 0.1 of additional 64: MS(ES) m/z 345 (M+H⁺), 367 (M+Na⁺); ¹H NMR [300 MHz, (CD₃)₂SO] d 3.26 (m, 4H), 3.44 (m, 4H), 3.60 (m, 2H), 3.80 (d,d, 1H), 4.05 (t, 1H), 4.69 (m, 1H), 7.22 (m, 2H), 7.54 (d, 1H).
A stirred mixture of [0779] 64 (0.39 g, 0.00113 mol) and triethylamine (0.214 mL, 0.00154 mol) in CH₂Cl₂(37 mL) was cooled, under nitrogen, in an ice bath and treated, portionwise during 5 min, with 3-nitrobenzenesulfonyl chloride (0.335 g, 0.00151 mol). The mixture was kept in the ice bath for 20 min and at ambient temperature for 18 h and concentrated in vacuo. A stirred solution of the residue in 2-propanol (25 mL) and acetonitrile (25 mL), under nitrogen, was treated with 30% NH₄OH (25 mL), warmed at 50-55° C. for 6 h and kept at ambient temperature for 48 h. It was concentrated to remove the organic solvents, diluted with water and extracted with CH₂Cl₂. The extract was washed with water and brine, dried (MgSO₄) and concentrated. Flash chromatography of the residue on silica gel with 6% MeOH—0.4% NH₄OH—CHCl₃gave 0.29 g of 35: ¹H NMR [300 MHz, (CD₃)₂SO] d 1.59 (broad s, 2H), 2.78 (m, 2H), 3.24 (m, 4H), 3.43 (m, 4H), 3.81 (d,d, 1H), 4.01 (t, 1H), 4.57 (m, 1H), 7.18 (m, 2H), 7.52 (m, 1H); MS(ES) m/z 344 (M+H⁺), 366 (M+Na⁺).
A stirred, ice cold suspension of [0780] 35 (0.28 g, 0.85 mmol) in a mixture of Et₃N (0.26 mL, 1.9 mmmol) and THF (10 mL) was treated with ethyl dithioacetate (0.11 mL, about 6 drops) and kept in the ice bath for 20 min and then at ambient temperature; the reaction was followed by TLC. After 20 h there was still a suspension and only partial reaction; additional THF (10 mL) and ethyl dithioacetate (3 drops) were added. After an additional 48 h the reaction was still incomplete; the suspension was treated with CH₂Cl₂(10 mL) and kept for 72 h. At this time almost complete solution and an almost complete conversion to product had been obtained. An additional drop of ethyl dithioacetate was added and the mixture was kept at ambient temperature for 5 d and concentrated in vacuo. The residue was mixed with EtOAc, washed with saturated NaHCO₃, water and brine, dried (MgSO₄) and concentrated. Crystallization of the residue from MeOH—EtOAc gave 0.209 g of 36: mp 197-198° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.42 (s, 3H), 3.24 (m, 4H), 3.43 (m, 4H), 3.78 (d,d, 1H), 3.88 (m, 2H), 4.12 (t, 1H), 4.92 (m, 1H), 7.18 (m, 2H), 7.50 (m, 1H), 10.37 (broad s, 1H); IR (mull) 3300, 3267, 1743 cm⁻¹; MS(ES) m/z 424 (M+Na⁺). Anal. calcd for C₁₆H₂₀FN₃O₄S₂: C, 47.87; H, 5.02; N, 10.47. Found: C, 47.84; H, 5.23; N, 10.28.

EXAMPLE 29

(S)-N-[[3-[3,5-Difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (38)

[0781]
A stirred mixture of [0782] 65 (1.8 g, 0.00396 mol), pyridine (30 mL) and absolute EtOH (3 mL), under nitrogen, was treated with hydroxylamine hydrochloride (1.44 g, 0.0207 mol), warmed to the reflux temperature during 2 h, refluxed for 3.5 h, kept at ambient temperature for 18 h and at reflux for 4 h. It was concentrated in vacuo and the residue was mixed with water, adjusted to pH 11 with saturated NaHCO₃and extracted with Et₂O. The extracts were washed with brine, dried (Na₂SO₄) and concentrated. Chromatography of the residue on silica gel with 5% MeOH—0.35% NH₄OH—CHCl₃gave 0.75 g of recovered 65 and 0.72 g of 66: ¹H NMR [300 MHz, (CD₃)₂SO] d 1.40 (s, 9H), 1.72 (broad s, 2H), 2.78 (m, 2H), 2.97 (m, 4H), 3.40 (m, 4H), 3.80 (d,d, 1H), 4.00 (t, 1H), 4.59 (m, 1H), 7.27 (d, 2H); MS(ES) m/z 413 (M+H⁺), 435 (M+Na⁺).
An ice cold, stirred mixture of [0783] 66 (0.75 g, 0.0018 mol) and triethylamine (0.315 mL, 0.00225 mol) in THF (12 mL), under nitrogen, was treated, dropwise with benzyl chloroformate (0.29 mL, 0.0020 mol), kept in the ice bath for 15 min and at ambient temperature for 2 h and concentrated in vacuo. The residue was mixed with CH₂Cl₂and washed with saturated NaHCO₃, water and brine, dried (Na₂SO₄) and concentrated. This residue was mixed with Et₂O and filtered to give 0.939 g of 67: mp 116-118° C.; ¹H NMR (300 MHz, CDCl₃) d 1.48 (s, 9H), 3.08 (m, 4H), 3.53 (m, 4H), 3.60 (m, 2H), 3.73 (m, 1H), 3.96 (t, 1H), 4.76 (m, 1H), 5.10 (s, 2H), 5.21 (m, 1H), 7.07 (d, 2H), 7.31 (s, 5H); MS(ES) m/z 547 (M+H⁺), 569 (M+Na⁺).
Compound [0784] 67 (0.805 g, 0.00147 mol) was added with stirring, portionwise during 5 min, under nitrogen, to ice cold trifluoroacetic acid (9 mL). The resulting solution was kept in the ice bath for 1 h and then concentrated under a stream of nitrogen. The residue was mixed with ice and saturated NaHCO₃and extracted with CH₂Cl₂; the extract was washed with water and brine, dried (Na₂SO₄) and concentrated to give 0.63 g of product. The combined aqueous layer was reextracted with EtOAc; the extracts were washed with water and brine, dried (Na₂SO₄) and conentrated to give additional product. The combined product amounted to 0.68 g of 68 which was used in the next reaction without further purification.
An ice cold, stirred mixture of [0785] 68 (0.68 g, 0.00152 mol), saturated NaHCO₃(15.2 mL) and acetone (40 mL), under nitrogen was treated, dropwise during 15 min, with a solution of benzyloxyacetyl chloride (0.29 mL, 0.0019 mol) in acetone (5 mL), kept at ambient temperature for 6 h, diluted with EtOAc and washed with water and brine. The extract was dried (MgSO₄) and concentrated in vacuo to give 0.72 g of 69: MS(ES) m/z 395 (M+H⁺), 617 (M+Na⁺); 1H NMR (300 MHz, CDCl₃) d 3.12 (m, 4H), 3.59 (m, 4H), 3.74 (m, 3H), 3.96 (t, 1H), 4.22 (s, 2H), 4.62 (s, 2H), 4.75 (broad s, 1H), 5.10 (s, 2H), 5.22 (m, 1H), 7.08 (d, 2H), 7.33 (m, 10H).
A mixture of [0786] 69 (0.72 g, 0.0012 mol), MeOH and 5% palladium-on-carbon catalyst (0.4 g) was hydrogenated at an initial pressure of 45 psi for 4 h. By TLC (8% MeOH—0.5% NH₄OH—CHCl₃) the starting material had been reduced and two products formed. 1M Hydrochloric acid (1.34 mL) was added and hydrogenation was continued at an initial pressure of 40 psi for 21 h. By TLC only the more polar product remained. The catalyst was removed by filtration and the filtrate was concentrated to give 0.40 g of 37: MS(ES) m/z 371 (M+H⁺), 393 (M+Na⁺); ¹H NMR [300 MHz, (CD₃)₂SO] d 3.02 (s, 4H), 3.20 (m, 2H), 3.43 (s, 2H), 3.56 (s, 2H), 3.84 (m, 1H), 3.84 (broad s), 4.10 (s, 2H), 4.14 (t, 1H), 4.96 (m, 1H), 7.26 (d, 2H), 8.41 (broad s, 3H).
A stirred suspension of [0787] 37 (0.38 g) in a solution of Et₃N (0.31 mL) and THF (10 mL), under nitrogen, was treated with ethyl dithioacetate (0.13 mL, about 7 drops) and kept at ambient temperature for 7 d; the reaction was followed by TLC (8% MeOH 0.5% NH₄OH—CHCl₃). Additional ethyl dithioacetate (2 drops) was added after 24 h; after 30 h CH₂Cl₂(10 mL) and ethyl dithioacetate (3 drops) were added; after 48 h additional triethylamine (0.3 mL) was added. The mixture was concentrated in vacuo and the residue was mixed with ice and saturated NaHCO₃an extracted with CH₂Cl₂. The extract was washed with water and brine, dried (MgSO₄) and concentrated. The residue was chromatographed on silica gel with 2.5% MeOH—CH₂Cl₂and the product was crystallized from MeOH to give 0.182 g of 38: mp 110-111° C. (dec); MS(ES) m/z 429 (M+H⁺), 451 (M+Na⁺); HRMS (FAB) calcd for C₁₈H₂₃F₂N₄O₄S (M+H⁺) 429.1408, found 429.1415; IR (DRIFT) 1760, 1652, 1639 cm⁻¹; [α²⁴ _D8° (MeOH).

EXAMPLE 30

(S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea (44)

[0788]
A solution of [0789] 26 (0.190 g, 0.685 mmol) in CH₂Cl₂(20 mL) was added, dropwise during 20 min, under nitrogen, to an ice cold, stirred solution of 1,1-thiocarbonyldi-2(1H)-pyridone (0.193 g, 0.831 mmol) in CH₂Cl₂(7 mL). The mixture was kept in the ice bath for 20 min and at ambient temperature for 2 h, diluted with CH₂Cl₂, washed with water and brine, dried (MgSO₄) and concentrated. Chromatography of the residue on silica gel with 10-15% CH₃CN—CH₂Cl₂gave 0.11 g of 79 which was used in the next reaction without further purification: MS(ES) m/z 320 (M+H⁺), 342 (M+Na⁺).
A stirred, ice cold solution of [0790] 79 (0.10 g, 0.31 mmol) in THF (15 mL) was treated with excess anhydrous ammonia and kept in the ice bath for 90 min. It was then evaporated under a stream of nitrogen to a volume of about 5 mL to give a solid which was collected by filtration and washed with cold THF to give 0.105 g of 44: mp 214-215° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 3.82 (m, 3H), 4.18 (t, 1H), 4.89 (broad s, 1H), 7.20 (broad s, 2H), 7.50 (d, 1H), 7.79 (m, 2H), 7.93 (t, 1H), 8.26 (s, 1H), 8.97 (s, 1H); MS(ES) m/z 337 (M+H⁺), 359 (M+Na⁺). Anal. calcd for C₁₃H₁₃FN₆O₂S: C, 46.42; H, 3.90; N, 24.99. Found: C, 46.22; H, 3.98; N, 24.55.

EXAMPLE 31

(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea (45)

[0791]
An ice cold, stirred solution of 1,1-thiocarbonyl-2(1H)-dipyridone (0.123 g, 0.530 mmol) in CH[0792] ₂Cl₂(5 mL), under nitrogen, was treated with a suspension of 29 (0.17 g, 0.4 mmol) in CH₂Cl₂(20 mL) and then during 10 min with a solution of triethylamine (0.111 mL, 0.8 mmol) in CH₂Cl₂(10 mL). It was kept in the ice bath for 30 min, at ambient temperature for 2 h and at <0° C. for 18 h. It was then diluted with CH₂Cl₂, washed with water and brine, dried (MgSO₄) and concentrated. The residue (80) was used without further purification in the next reaction. A sample of 80 that was purified by flash chromatography on silica gel with 10-20% acetonitrile-CH₂Cl₂had: ¹H NMR (300 MHz, CDCl₃) d 1.60 (broad s), 3.07 (m, 4H), 3.45 (m, 2H), 3.85 (m, 4H), 3.97 (d,d, 1H), 4.16 (t, 1H), 4.21 (s, 2H), 4.82 (m, 1H), 6.95 (t, 1H), 7.13 (d,d, 1H), 7.47 (d,d, 1H); MS m/z 395 (M+H⁺); 417 (M+Na⁺).
Excess anhydrous ammonia was bubbled into a stirred, ice cold solution of [0793] 80 (crude product from the previous reaction) in THF (25 mL) and the mixture was kept in the ice bath for 90 min and concentrated under a stream of nitrogen. The residue was chromatographed on silica gel with 5% MeOH—0.4% NH₄OH—CHCl₃and the product was crystallized from acetonitrile to give 0.0544 g of 45: mp 209-210° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 294 (broad s, 4H), 3.47 (broad s, 2H), 3.60 (broad s, 2H), 3.78 (broad s, 3H), 4.07 (t, 1H), 4.10 (d, J=5.5 Hz, 2H), 4.63 (t, J=5.5 Hz, 1H), 4.81 (broad s, 1H), 7.05 (t, 1H), 7.16 (d,d, 1H), 7.15 (broad s, 2H), 7.49 (d,d, 1H), 7.91 (t, 1H); IR (mull) 3443, 3403, 3321, 3202, 3081, 1753, 1655, 1648 cm⁻¹; HRMS (FAB) calcd for C₁₇H₂₃FN₆O₄S (M+H⁺) 412.1454, found 412.1447. Anal. calcd for C₁₇H₂₂FN₅O₄S: C, 49.63; H, 5.39; N, 17.02. Found: C, 49.63; H, 5.48; N, 16.99.

EXAMPLE 32

(S)-N-[[3-[1-(Hydroxyacetyl)-5-indolinyl]-2-oxo-5-oxazolidinyl]methyl]thiourea (46)

[0794]
An ice cold, stirred solution of 1,1-thiocarbonyldi-2(1H)-pyridone (0.096 g, 0.41 mmol) in CH[0795] ₂Cl₂(5 mL) was treated with a suspension of 27 (0.10 g, 0.34 mmol) in CH₂Cl₂(15 mL) and then with 0.05 mL (0.36 mmol) of triethylamine. It was kept in the ice bath for 30 min and at ambient temperature for 2 h, diluted with CH₂Cl₂, washed with water and brine, dried (MgSO₄) and concentrated. Chromatography of the residue on silica gel with 20-40% CH₃CN—CH₂Cl₂gave 0.04 g of 81.
Excess anhydrous ammonia was bubbled into an ice cold solution of [0796] 81 (0.04 g) in THF (30 mL) and the mixture was kept in the ice bath for 80 min and concentrated under a stream of nitrogen. The residue was crystallized from CH₃CN to give 0.0151 g of 46: mp 214-215° C. (dec); MS (FAB) m/z 351 (M+H⁺), 350 (M⁺), 319, 304, 147; HRMS (FAB) calcd for C₁₅H₁₉N₄O₄S (M+H⁺) 351.1127, found 351.1130; IR (DRIFT) 3329, 3296, 3196, 1746, 1655, 1626 cm⁻¹.

EXAMPLE 33

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea, thiomorpholine S-oxide (47)

[0797]
A suspension of [0798] 33 (0.30 g, 0.92 mmol) in CH₂Cl₂(7 mL) was added, during 20 min, to an ice cold, stirred mixture of 1,1-thiocarbonyldi-2(1H)-pyridone (0.258 g, 1.11 mmol) and CH₂Cl₂(20 mL). The mixture was kept in the ice bath for 20 min and at ambient temperature for 2 h, mixed with CH₂Cl₂(50 mL), washed with water and brine, dried (MgSO₄) and concentrated. Chromatography of the product on silica gel with 20-50% CH₃CN—CH₂Cl₂gave 0.27 g of 82 which was used in the next reaction: MS(ES) m/z 370 (M+H⁺), 392 (M+Na⁺).
A stirred, ice cold solution of [0799] 82 (0.27 g, 0.73 mmol) in THF (15 mL), under nitrogen, was treated with excess anhydrous ammonia, kept in the ice bath for 1 h and concentrated; crystallization of the residue from MeOH gave 0.175 g of 47; mp 212-213° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.83 (m, 2H), 3.01 (m, 2H), 3.17 (m, 2H), 3.50 (t, 2H), 3.78 (broad s, 3H), 4.08 (t, 1H), 4.80 (broad s, 1H), 7.17 (m, 2H), 7.17 (broad s, 2H), 7.50 (d, 1H), 7.90 (t, 1H); MS(ES) m /z 409 (M+Na⁺); IR (mull) 3335, 3284, 3211, 3175, 3097, 1750, 1630 cm⁻¹. Anal. calcd for C₁₅H₁₉FN₄O₃S₂: C, 46.62; H, 4.95; N, 14.50. Found: C, 46.50; H, 4.95; N, 14.40.

EXAMPLE 34

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl-S-methyldithiocarbamate (48)

[0800]
An ice cold, stirred mixture of [0801] 39 (0.59 g, 0.0020 mol), EtOH (1.5 mL), water (2 drops) and triethylamine (0.613 mL, 0.00440 mol), under nitrogen, was treated with carbon disulfide (0.066 mL, 0.0011 mol) and kept in the ice bath for 2 h and at ambient temperature for 18 h. (A solution was obtained after the addition of carbon disulfide; a white precipitate began to form soon after the mixture was warmed to ambient temperature.) The thick suspension was treated, dropwise during 2 min, with a solution of methyl iodide (0.137 mL, 0.00220 mol) in EtOH (2 mL) and the mixture was kept at ambient temperature for 1.5 h and concentrated in vacuo. A solution of the residue in EtOAc was washed with saturated NaHCO₃, water and brine, dried (MgSO₄) and concentrated. The residue was chromatographed on silica gel with 1.8% MeOH—CH₂Cl₂and the product was crystallized from EtOAc to give 0.197 g of 48: mp 154-155° C.; IR (mull) 3354, 3346, 1726 cm⁻¹. Anal. calcd for C₁₆H₂₀FN₃O₃S₂: C, 49.85; H, 5.23; N, 10.90. Found: C, 49.73; H, 5.25; N, 10.82.

EXAMPLE 35

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl-O-methylthiocarbamate (50)

[0802]
A stirred mixture of [0803] 48 (0.200 g, 0.518 mmol), sodium methoxide (0.003 g, 0.06 mmol) and MeOH (5 mL), under nitrogen, was refluxed for 4 h and kept at ambient temperature for 18 h. It was found that the starting material and product had similar mobilities on TLC. the reaction was therefore followed by MS(ES). Starting material was still present. The mixture was refluxed for 3 h, additional sodium methoxide (0.005 g) was added and reflux was continued for 2 h. It was kept at ambient temperature for 18 h, refluxed for 1 h, kept at ambient temperature 1.5 h and concentrated in vacuo. The residue was mixed with ice, the pH was adjusted to 9-10 with 1M KHSO₄and saturated NaHCO₃and the mixture was extracted with CH₂Cl₂. The extract was washed with water and brine, dried (MgSO₄) and concentrated. The residue was chromatographed on silica gel with 5% acetone-CH₂Cl₂and the product was crystallized from EtOAc-hexane to give 0.107 g of 50: mp 128-129° C.; MS(ES) m/z 370 (M+H⁺), 392 (M+Na⁺); IR (DRIFT) 3282, 3251, 1753, 1735 cm⁻¹; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.94 (m, 4H), 3.47, 374 (m,m, 7H), 3.86, 3.91 (s,s, 3H), 4.10 (m, 1H), 4.73, 4.86 (m,m, 1H), 7.05 (t, 1H), 7.16 (d,d, 1H), 7.47 (d,d, 1H), 9.41, 9.50 (s,s, 1H). Anal. calcd for C₁₆H₂₀FN₃O₄S: C, 52.02; H, 5.46; N, 11.38. Found: C, 51.97; H, 5.49; N, 11.35.
When in the procedure of Example 35 an appropriate amount of sodium ethoxide was substituted for sodium methoxide, the compound of Example 36 below in Table A was obtained. [0804]
When in the procedure of Example 1 an appropriate amount of (S)-N-[[3-[3-fluoro-4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isopropylcarboxamide, (S)-N-[[3-[3-fluoro-4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropylcarboxamide, or (S)-N-[[3-[3,5-difluoro-4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide was substituted for (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (Compound [0805] 11) and the general procedures of Example 1 was followed, the compounds of Examples 37, 38 and 39 respectively as set forth below in Table A were obtained. The isopropylcarboxamide and the cyclopropylcarboxamide are obtained by following the procedure in Example 5 of U.S. Pat. No. 5,688,792 only substituting isobutyric anhydride and cyclopropane carbonyl chloride respectively for acetic anhydride in step 7. The acetamide is obtained as described in U.S. Pat. No. 5,688,792 at Example 4.

When in the procedure of Example 5, step B, an excess amount of dimethylamine in THF is substituted for anhydrous ammonia, the compound of Example 40 set forth below in Table A is obtained.

TABLE A

Example No.	Compound	R, R′


36	(S)—N-[[3-[3-Fluoro-4-(4-morpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- ethylthiocarbamate; mp 120° C., MS(ES) m/z 384(M + H⁺). Anal. calcd for C₁₇H₂₂FN₃O₄S: C, 53.25; H, 5.78; N, 10.96. Found: C, 53.23; H, 5.82; N, 10.92.	R = H, R′ = OC₂H₅

37	(S)—N-[[3-[3-Fluoro-4-(4-morpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide; mp 152-153° C. (dec.); Anal. calcd for C₁₈H₂₄FN₃O₃S: C, 56.67; H, 6.34; N, 11.02. Found: C, 56.58; H, 6.41; N, 10.81	R = H, R′ = CH(CH₃)₂

38	(S)—N-[[3-[3-Fluoro-4-(4-morpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropane-carbothioamide; mp 155-156° C.; Anal. calcd for C₁₈H₂₂FN₃O₃S: C, 56.98; H, 5.84; N, 11.07. Found: C, 56.98; H, 5.85; N, 10.97

39	(S)—N-[[3-[3,5-Difluoro-4-(4-morpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- thioacetamide	R = F, R′ = CH₃

40	(S)—N-[[3-[3-Fluoro-4-(4-morpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′- dimethylthiourea	R = H, R′ = N(CH₃)₂

PREPARATION Z Methyl Dithiopropionate

A stirred mixture of magnesium turnings (12.6 g, 0.520 g atom) and THF (100 mL) under nitrogen is treated with a crystal of iodine and about 5% of a solution of bromoethane (30.0 mL, 0.40 mol) in THF (200 mL). When the reaction starts, the remainder of the bromoethane solution is added, dropwise at a rate sufficient to maintain a gentle reflux. After the addition, stirring is continued for 1 hour; the resulting solution is cooled to −20° C. and treated, during 10 minutes with carbon disulfide (24.0 mL, 0.40 mol). The mixture is warmed to 15° C., treated with methyl iodide (28.0 mL, 0.45 mol) and kept at 60° C. for 1 hour. It is then cooled in an ice bath, treated with ice and extracted with Et[0807] ₂O. The extract is washed with brine, dried (MgSO₄) and concentrated. Distillation of the residue gives 34.0 g of the titled product, bp 48-52° C. (12 mmHg).
The following methyl dithio compounds were obtained when the appropriate alkyl magnesium bromide was substituted for ethyl magnesium bromide in the above procedure: [0808]

The following methyl dithio compounds were obtained when the appropriate alkyl magnesium bromide was substituted for ethyl magnesium bromide in the above procedure:

TABLE B

	Rs =


(b)	(CH₃)₂CH—	(h)

(c)		(i)

(d)	CH₃CH₂CH₂—	(j)

(e)		(k)

(f)		(l)

(g)	(CH₃)₃C—CH₂—	(m)

When following the general procedure of Example 27, step 4, an appropriate amount of the amine listed below is reacted with the dithio compound listed below the respective compounds, Examples 41 to 61 of Table C are obtained. [0810]

When following the general procedure of Example 25, step 6, an appropriate amount of the amine listed below is reacted with the dithio compound listed below, the respective compounds, Examples 62 to 67, of Table C are obtained.

TABLE C


Example			Dithio Compound
No.	Compound	Amine	(from Preparation Z)


41	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholine S-oxide; mp 196-197° C.;
#Anal. calcd for C₁₇H₂₂FN₃O₃S₂: C, 51.11; H, 5.55; N, 10.52; S, 16.05. Found: C, 50.99; H, 5.60; N, 10.55; S, 15.75		Z(a)

42	(S)—N-[[3-[3-Fluoro-4-(4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholine S-oxide; mp 195-196° C.;
#Anal. calcd for C₁₈H₂₄FN₃O₃S₂: C, 52.28; H, 5.85; N, 10.16; S, 15.51. Found: C, 52.24; H, 5.97; N, 10.16; S, 15.28		Z(b)

43	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholine S-oxide; mp 109-110° C.; Anal. calcd for
#C₁₈H₂₂FN₃O₃S₂: C, 52.54; H, 5.39; N, 10.21; S, 15.58. Found: C, 52.48; H, 5.51; N, 10.28; S, 15.29		Z(c)

44	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- butanethioamide, thiomorpholine S-oxide		Z(d)

45	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide, thiomorpholine S-oxide		Z(e)

46	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylbutanethioamide, thiomorpholine S-oxide		Z(f)

47	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide, thiomorpholine S-oxide		Z(g)

48	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothio- amide, thiomorpholine S-oxide		Z(h)

49	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- cyclopentanecarbothio- amide, thiomorpholine S-oxide		Z(i)

50	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclohexanecarbothio- amide, thiomorpholine S-oxide		Z(j)

51	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethio- amide, thiomorpholine S-oxide		Z(k)

52	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethio- amide, thiomorpholine S-oxide		Z(l)

53	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylethanethio- amide, thiomorpholine S-oxide		Z(m)

54	(S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- thioacetamide, thiomorpholine S-oxide		Ethyl dithioacetate

55	(S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholine S-oxide		Z(a)

56	(S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholine S-oxide		Z(b)

57	(S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholine S-oxide		Z(c)

58	(S)—N-[[3-[4-(4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- thioacetamide, thiomorpholine S-oxide		Ethyl dithioacetate

59	(S)—N-[[3-[4-(4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholine S-oxide		Z(a)

60	(S)—N-[[3-[4-(4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholine S-oxide		Z(b)

61	(S)—N-[[3-[4-(4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholine S-oxide		Z(c)

62	(S)—N-[[3-[3,5-Difluoro- 4-(4-hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]propanethio- amide		Z(a)

63	(S)—N-[[3-[3,5-Difluoro- 4-(4-hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-2-methyl- propanethioamide		Z(b)

64	(S)—N-[[3-[3,5-Difluoro- 4-(4-hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]cyclopropane- thioamide		Z(c)

65	(S)—N-[[3-[3-[4- (hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]propanethio- amide		Z(a)

66	(S)—N-[[3-[3-[4- (hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-2-methyl- propanethioamide		Z(b)

67	(S)—N-[[3-[3-[4- (hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]cyclopropane- carbothioamide		Z(c)

When following the procedure of Example 28, step 3, an appropriate amount of the amine listed below is reacted with the dithio compound listed below, the respective compounds, Examples 68 to 78 of Table D are obtained.

TABLE D


Example			Dithio Compound
No.	Compound	Amine	(see Preparation Z)


68	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholine S,S- dioxide		Z(a)

69	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholine S,S-dioxide		Z(b)

70	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholine S,S-dioxide		Z(c)

71	(S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]- methyl]thioacetamide, thiomorpholine S,S- dioxide		Ethyl dithioacetate

72	(S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholine S,S- dioxide		Z(a)

73	(S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholine S,S-dioxide		Z(b)

74	(S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholine S,S-dioxide		Z(c)

75	(S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]thioacetamide, thiomorpholine S,S- dioxide		Ethyl dithioacetate

76	(S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]propanethio- amide, thiomorpholine S,S-dioxide		Z(a)

77	(S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]-2-methyl- propanethioamide, thiomorpholine S,S- dioxide		Z(b)

78	(S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]cyclopropane- carbothioamide, thiomorpholine S,S- dioxide		Z(c)

When following the procedure of Example 26, an appropriate amount of the amine listed below is reacted with the dithio compound listed below the respective compounds, Examples 79 to 99 of Table E are obtained.

TABLE E


Example			Dithio Compound
No.	Compound	Amine	(See Preparation Z)


79	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide		Z(a)

80	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide		Z(b)

81	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide		Z(c)

82	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- butanethioamide		Z(d)

83	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide		Z(e)

84	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylbutanethioamide		Z(f)

85	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide		Z(g)

86	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothio- amide		Z(h)

87	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopentanecarbothio- amide		Z(i)

88	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclohexanecarbothio- amide		Z(j)

89	(S)—N-[[3-[3-5 Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethio- amide		Z(k)

90	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethio- amide		Z(l)

91	(S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylethanethio- amide		Z(m)

92	(S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- thioacetamide		Ethyl dithioacetate

93	(S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide		Z(a)

94	(S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide		Z(b)

95	(S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide		Z(c)

96	(S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]thioacetamide		Ethyl dithioacetate

97	(S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]propanethio- amide		Z(a)

98	(S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]-2-methyl- propanethioamide		Z(b)

99	(S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]cyclopropane- carbothioamide		Z(c)

The amine utilized in Examples 41 to 53 is prepared as described in Example 27, step 3. The amine utilized in Examples 54 to 57 is prepared by the procedure of Example 27, steps 1 to 3 by substituting the appropriate (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methanol for compound [0814] 62 in step 1 of Example 27.
The amine utilized in Examples 58 to 61 is prepared by the procedure of Example 27, steps 1 to 3 by substituting the appropriate (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methanol for compound [0815] 62 in Example 27, step 1. The appropriate oxazolidinyl methanol compound is obtained by following the procedure of Example 1 in U.S. Pat. No. 5,688,792, steps 1 through 3, only substituting 4-fluoronitrobenzene for 3,4-difluoronitrobenzene in step 1 thereof.
The amine utilized in Examples 62 to 64 is prepared as compound 37 in Example 29 from the amide, [0816] 65, which is prepared as described in Example 32 of U.S. Pat. No. 5,700,799. The amine utilized in Examples 65 to 67 is prepared by the general procedure of Example 29 from the following amide, the preparation of which is decribed in Example 3 of U.S. Pat. No. 5,700,799:
The amine utilized in Examples 68 to 70 is prepared as described in step 2 of Example 28 above. [0817]
The amine utilized in Examples 71 to 74 is prepared as described in Example 28 by substituting (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methanol for compound [0818] 62 in step 1 and following the procedure of steps 1 and 2. The appropriate oxazolidinyl methanol compound is prepared by following the general procedure of Example 4 of U.S. Pat. No. 5,688,792, steps 1 through 4, only substituting thiomorpholine for morpholine in step 1 thereof.
The amine utilized in Examples 75 to 78 is prepared as described in Example 28, step 1, above by substituting (S)-N-[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5oxazolidinyl]methanol for compound [0819] 62 in step 1. The appropriate oxazolidinyl methanol is obtained by following the procedure of Example 1 in U.S. Pat. No. 5,688,792, steps 1 through 3, only substituting 4-fluoronitrobenzene for 3,4-difluoronitrobenzene in step 1 thereof.
The amine utilized in Examples 79 to 91 is prepared as described in Example 1, step 4, of U.S. Pat. No. 5,688,792. The amine utilized in Examples 92 to 95 is prepared as described in Example 4 of U.S. Pat. No. 5,688,792 only substituting thiomorpholine for morpholine in step 1 thereof. The amine utilized in Examples 96 to 99 is prepared by the procedure of Example 1 of U.S. Pat. No. 5,688,792, only substituting 4-fluoronitrobenzene for 3,4-difluoronitrobenzene in step 1 thereof. [0820]

EXAMPLE 100

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate, thiomorpholine S-oxide

[0821]
A solution of 201 mg (0.554 mmol) of (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanate, thiomorpholine s-oxide compound [0822] 82 from Example 33, step 1, in methanol (10 mL) is refluxed, under nitrogen for 18 hours and cooled. The solid is collected by filtration to give 0.138 g of the titled product. m.p. 208-209° C.; Anal. calcd for C₁₆H₂₀FN₃O₄S₂: C, 47.87; H, 5.02; N, 10.47. Found: C, 47.81; H, 5.04: N, 10.49.

When in the procedure of Example 100 the thioisocyanate listed below is substituted for compound 82 the products listed below as Examples 101 to 109 are obtained.

TABLE F


Isothiocyanate

			Ex-
			ample
Rc	Ra	Rb	No.	Compound

OS	F	F	101	(S)—N-[[3-[3,5-Difluoro-4-(4-
				thiomorpholinyl)phenyl]-2-oxo-5-
				oxazolidinyl]methyl]-O-methylthio-
				carbamate, thiomorpholine S-oxide
OS	H	H	102	(S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-
				2-oxo-5-oxazolidinyl]methyl]-O-methyl-
				thio-carbamate, thiomorpholine S-oxide
O₂S	H	F	103	(S)—N-[[3-[3-Fluoro-4-(4-thiomorpho-
				linyl)-phenyl]-2-oxo-5-oxazolidinyl]meth-
				yl]-O-methylthiocarbamate, thio-
				morpholine S,S-dioxide
O₂S	F	F	104	(S)—N-[[3-[3,5-Difluoro-4-(4-
				thiomorpholinyl)phenyl]-2-oxo-5-
				oxazolidinyl]methyl]-O-methylthio-
				carbamate, thiomorpholin S,S-dioxide
O₂S	H	H	105	(S)—N-[[3-[4-(4-thiomorpholinyl)phenyl]-
				2-oxo-5-oxazolidinyl]methyl]-O-methyl-
				thiocarbamate, thiomorpholine
				S,S-dioxide
S	H	F	106	(S)—N-[[3-[3-Fluoro-4-(4-thio-
				morpholinyl)-phenyl]-2-oxo-5-oxa-
				zolidinyl]methyl]-O-methylthiocarbamate
S	F	F	107	(S)—N-[[3-[3,5-Difluoro-4-(4-thiomorph-
				olinyl)phenyl]-2-oxo-5-oxazolidinyl]-
				methyl]-O-methylthiocarbamate
S	H	H	108	(S)—N-[[3-[4-(4-thiomorpholinyl)phenyl]-
				2-oxo-5-oxazolidinyl]methyl]-O-methyl-
				thiocarbamate
	H	H	109	(S)—N-[[3-[3-Fluoro- 4-(4-(hydroxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate

When in the procedure of Example 100 an appropriate amount of ethanol and isopropyl alcohol were substituted for methanol, the following respective compounds were obtained: [0824]
EXAMPLE 110: (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate, thiomorpholine S-oxide. m.p. 198-199° C.; Anal. calcd for C[0825] ₁₇H₂₂FN₃O₄S₂: C, 49.14; H, 5.34; N, 10.11. Found: C, 49.06; H, 5.27; N, 10.10.
EXAMPLE 111: (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate, thiomorpholine S-oxide. m.p. 180-181° C.; Anal. calcd for C[0826] ₁₈H₂₄FN₃O₄S₂: C, 50.33; H, 5.63; N, 9.78. Found: C, 50.29; H, 5.69; N, 9.82.
When in the procedure of Example 114 an appropriate amount of (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]isothiocyanate is substituted for compound [0827] 82 and ethanol or isopropyl alcohol is substituted for methanol, the following respective products are obtained:
EXAMPLE 112: (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate; [0828]
EXAMPLE 113: (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate; [0829]
EXAMPLE 114: (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]N-methylthiourea, thiomorpholine S-oxide. [0830]
A stirred suspension of 240 mg (0.650 mmol) of compound [0831] 82 from Example 33, step 1 in THF (5 mL) at 0° C. is treated with a 2M solution of methylamine in THF (0.42 mL, 0.845 mmol) and kept at ambient temperature for 18 hours. The solid is collected by filtration to give 0.221 g of the titled product.
Following the procedure of Example 114, only substituting an appropriate amount of dimethylamine and azetidine for methylamine, the following compounds are obtained: [0832]
EXAMPLE 115: (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]N′,N′-dimethylthiourea, thiomorpholine S-oxide; Anal. Calcd for C[0833] ₁₇H₂₃FN₄O₃S₂, C, 49.26; H, 5.59; N, 13.52. Found C, 49.11; H, 5.57; N, 13.40; mp 180-182° C.
EXAMPLE 116: (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide, thiomorpholine S-oxide; Anal. Calcd for C[0834] ₁₈H₂₃FN₄O₃S₂, C, 50.69; H, 5.43; N, 13.14. Found: C, 50.79; H, 5.45; N, 12.82; mp 213-214° C.
When in the procedure of Example 114 an appropriate amount of (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanate is substituted for compound [0835] 82, the following compound is obtained:
EXAMPLE 117: (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]methyl-N′-methylthiourea. [0836]
When in the procedure of Example 117 an appropriate amount of dimethylamine and azetidine are substituted for methylamine, the following respective products are obtained: [0837]
EXAMPLE 118: (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea; [0838]
EXAMPLE 119: (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide. [0839]
When in the procedure of Example 33 an appropriate amount of compound [0840] 31 from Example 26 is substituted for compound 33 and the general procedure of steps 1 and 2 of Example 33 are followed, the following compound is obtained.
EXAMPLE 120: (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea. [0841]
EXAMPLE 121: (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl-2-oxo-5-oxazolidinyl]methyl]propanethioamide [0842]
A stirred mixture of 200 mg (0.514 mmol) of [0843] 29 methyl dithiopropionate (247 mg, 2.06 mmol), triethylamine (0.58 mL, 4.11 mmol), THF (5.4 mL) and methylene chloride (5.4 mL) is kept, under nitrogen, for 3 days, diluted with water and extracted with methylene chloride. The extracts are dried (MgSO₄) and concentrated. Chromatography of the residue on silica gel and crystallization of the product from methanol gives 0.132 g of the titled product. m.p. 190-191° C.; Anal. calcd for C₁₉H₂₅FN₄O₄S: C, 53.76; H, 5.94; N, 13.20; S, 7.55. Found: C, 53.66; H, 5.94; N, 13.20; S, 7.37.

Following the procedure of Example 121 only substituting dithio compounds Z (b) to Z (m) from Preparation Z above for methyl dithiopropionate, the following compounds are obtained.

TABLE G

Ex-
ample
No.	Compound
122	(S)—N-[[3-[3-Fluoro-4-[4-(hydroxy-	R = CH(CH₃)₂
	acetyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-2-methylpropane-
	thioamide; Anal. calcd for
	C₂₀H₂₇FN₄O₄S: C, 54.78; H, 6.21; N,
	12.78; S, 7.31. Found: C, 54.67; H,
	6.34; N, 12.41; S, 7.15
123	(S)—N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclopropane- carbothioamide; mp 179-181° C.; Anal. calcd for C₂₀H₂₅FN₄O₄S: C, 55.03; H, 5.77; N, 12.84; S, 7.34. Found: C, 55.15; H, 5.72; N, 12.76; S, 7.09

124	(S)—N-[[3-[3-Fluoro-4-[4-(hydroxy-	R = CH₂—CH₂—CH₃
	acetyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]butanethioamide

125	(S)—N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-3-methylbutane- thioamide

126	(S)—N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylbutane- thioamide

127	(S)—N-[[3-[3-Fluoro-4-[4-(hydroxy-	R = CH₂—C(CH₃)₃
	acetyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-3,3-dimethyl-
	butanethioamide
128	(S)—N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclobutane- carbothioamide

129	(S)—N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclopentane- carbothioamide

130	(S)—N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclohexane- carbothioamide

131	(S)—N-[[3-[3-Fluoro-4-[4-hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclopropyl- ethanethioamide

132	(S)—N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclobutyl- ethanethioamide

133	(S)—N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclopentyl- ethanethioamide

When in the procedure of Example 100 an appropriate amount of compound [0845] 80 from Example 31 is substituted for compound 82, and ethanol or isopropyl alcohol is substituted for methanol, the following respective compounds are obtained:
EXAMPLE 134: (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate; [0846]
EXAMPLE 135: (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-iso-propylthiocarbamate; [0847]
EXAMPLE 136: (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea. [0848]
When in the procedure of Example 114 an appropriate amount of compound [0849] 80 from Example 31 is substituted for compound 82, the title compound is obtained.
Following the procedure of Example 114 only substituting an appropriate amount of compound [0850] 80 from Example 31 for compund 82 and substituting an appropriate amount of dimethylamine and azetidine for methylamine, the following compounds, Examples 137 and 138, are obtained:
EXAMPLE 137: (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea; [0851]
EXAMPLE 138: (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide. [0852]

EXAMPLE 139

(S)-N-[[3-[3,5-Difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate.

Part A: Following the procedure of Example 33, step 1, only substituting an appropriate amount of compound [0853] 37 from Example 29, step 5, for compound 33, (S)-N-[[3,5-[3-difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanate is obtained.
Part B: Upon substitution of an appropriate amount of (S)-N-[[3-[3,5-difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanate for compound [0854] 82 in the general procedure of Example 100, the title compound is obtained.

EXAMPLE 140

(S)-N-[[3-[4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate

Part A: Following the procedure of Example 33, step 1, only substituting an appropriate amount of (S)-N-[[3-[4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]amine for compound 33, (S)-N-[[3-[4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanate is obtained. [0855]
Part B: Upon substituting an appropriate amount of (S)-N-[[3-[4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanate for compound [0856] 82 in the general procedure of Example 100, the title compound is obtained.

EXAMPLE 141

(S)-N-[[-3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide

[0857]
An ice cold, stirred solution of 30.4 g (70.8 mmol) of starting material [0858] 58 from Example 25, step 1), and triethylamine (15.4 mL, 110 mmol) in methylene chloride (2570 mL) is treated with m-nitrobenzenesulfonyl chloride (18.8 g, 84.9 mmol) and kept, under nitrogen, at ambient temperature (24° C.) for 24 hours. Additional m-nitrobenzenesulfonyl chloride (1.88 g) and triethylamine (1.54 mL) are added and the mixture is kept for one additional day at ambient temperature, washed with water, saturated sodium bicarbonate and brine, dried (Na₂SO₄) and concentrated to give an oily product, 85. The alcohol, 58 is prepared according to the procedures of Brickner (J. Med. Chem. 1996, 39, 673-679), see compound 5a therein.
A stirred mixture of [0859] 85, acetonitrile (1270 mL), isopropanol (1270 mL) and ammonium hydroxide (1270 mL) is kept at ambient temperature for 3 days and concentrated in vacuo. Chromatography of the residue on silica gel with 0.5% NH₄OH-1% MeOH—CH₂Cl₂gives 22.4 g of the amine, 86.
An ice cold, stirred solution of the amine [0860] 86 in THF (650 mL) is treated, during 20 mintues with a solution of di-tert-butyl dicarbonate (12.0 g, 55.2 mmol) in THF (90 mL). The mixture is kept at ambient temperature for 18 hours and concentrated in vacuo. The residue, dissolved in methylene chloride, is washed with dilute sodium bicarbonate, dried (MgSO₄) and concentrated. Crystallization of the residue from methanol-ethyl acetate gives 20.0 g of the Boc protected amine. Additional product (4.1 g) is obtained by chromatographing the mother liquors on silica gel with 1-2% methanol-methylene chloride.
A solution of the protected amine, [0861] 87, (5.00 g, 9.46 mmol) in ethanol (150 mL) is treated with 10% palladium-on-carbon catalyst (1.0 g) and hydrogenated at an initial pressure of 30 psi for 3 hours. The catalyst is removed by filtration through Celite and the filtrate was concentrated to give 3.66 g of compound 88.
A stirred solution of compound [0862] 88 (1.10 g, 2.79 mmol) in pyridine (10 mL) is treated with acetic anhydride (289 μL, 3.07 mmol), kept at ambient temperature for 2 hours and concentrated in vacuo. A solution of the residue in methylene chloride is washed with dilute hydrochloric acid, dried (MgSO₄) and concentrated to give 1.23 g of compound 89: MS m/z 436 (M⁺).
An ice cold, stirred 4N solution of HCl in dioxane (10 mL) is treated with compound [0863] 89 (1.10 g, 2.52 mmol). The mixture is kept in the ice bath for 30 minutes and at ambient temperature for 1 hour. It was then mixed with methylene chloride and concentrated. The residue is triturated with methylene chloride to give 1.03 g of the amine hydrochloride.
A stirred mixture of compound P-90 (250 mg), triethylamine (0.75 mL, 5.36 mmol), ethyl dithioacetate (307 μL, 2.68 mmol), methylene chloride (7.4 mL) and THF (7.4 mL) is kept at ambient temperature for 1 day, concentrated and chromatographed on silica gel with mixtures of methanol-methylene chloride containing 1-2% methanol. Crystallization of the product from ethyl acetate-heptane gives 0.160 g of the titled product: Anal. calcd for C[0864] ₁₈H₂₃FN₄O₃S: C, 54.81; H, 5.88; N, 14.20; S, 8.13. Found: C, 54.92; H, 5.95; N, 14.08; S, 7.94; mp 158° C.
When in the general procedure of Example 141 an appropriate amount of [0865]
is substituted for compound [0866] 58 and the procedure of steps 1 through 6 are followed, the respective amine compounds P-91 and P-92 listed below are obtained:
The alcohols above designated as x and y are prepared according to the procedures of Brickner (J. Med. Chem., 1996, 39, 673-679), by substituting an appropriate amount of 2,6-difluoro-4-nitrobenzene (trifluoromethane) sulfonate and 4-fluoronitrobenzene respectively for 3,4-difluoronitrobenzene in the preparation of [0867] 2a therein.
When in the procedure of Example 141 an appropriate amount of x or y is substituted for compound [0868] 58 and the procedures of steps 1 through 4 are followed, the following Boc protected compounds listed below are obtained.
When in the procedure of Example 141, step 5, an appropriate amount of compound [0869] 88, compound x-b or compound y-b is treated with the reagent listed below and the general procedures of step 5 and step 6 are followed, the amines listed below as Preparation P-93 through P-128 are obtained.
The amine compound set forth below as P-129 is obtained by refluxing for 6 days a solution of compound [0870] 88 (1.00 g, 2.54 mmol), sulfamide (305 mg, 3.18 mmol) and 1,2-dimethyoxyethane (6 mL). The solid which precipitates is collected by filtration and chromatographed on silica gel with 5% methanol-methylene chloride. Crystallization of the product from methanol-methylene chloride gives 0.551 g of the sulfamoyl derivative, which is used in step 6 of Example 141 to give P-129. When compounds x-b and y-b are substituted for compound 88 and this general procedure is followed, Preparations P-130 and P-131 respectively set forth below are obtained.
Following the general procedures of steps 5 and 6 of Example 141 only in step 5 substituting chloroacetonitrile or 2-fluoroethyl bromide respectively for acetic anhydride and using potassium carbonate in acetonitrile, and using either compound [0871] 88, compound x-b or compound y-b, the respective amines set forth below as Preparations P-132 to P-137 are obtained.

The amine compound set forth below as Preparation P-138 is obtained by combining compound 88 (1.10 g, 2.75 mmol) set forth in step 5 of Example 141 with N-formylbenzotriazole (493 mg, 3.35 mmol) in THF (30 mL) and the mixture is kept at ambient temperature for 18 hours. The mixture is concentrated and the residue in methylene chloride is washed with 1N sodium hydroxide and dilute sodium chloride, dried (MgSO₄), concentrated, and chromatographed on silica gel with mixtures of methanol and methylene chloride containing 1-2% methanol to give 1.09 g of the N-formyl derivative which is utilized in the general procedure of step 6 of Example 141 to give Preparation P-138. When in this foregoing procedure compound x-b or compound y-b is substituted for compound 88, Preparations P-139 and and P-140 as set forth below are obtained.

	Boc				Preparation
Reagent	Compound	R	R″	R′	No.


methoxyacetylchloride	88 x-b y-b		H F H	F F H	P-93 P-94 P-95

cyanoacetyl chloride	88 x-b y-b		H F H	F F H	P-96 P-97 P-98

acetoxyacetyl chloride	88 x-b y-b		H F H	F F H	P-99 P-100 P-101

benzyloxyacetyl chloride	88 x-b y-b		H F H	F F H	P-102 P-103 P-104

methyl chloroformate	88 x-b y-b		H F H	F F H	P-105 P-106 P-107

methanesulfonyl chloride	88	CH₃SO₂—	H	F	P-108
	x-b		F	F	P-109
	y-b		H	H	P-110
ethanesulfonyl chloride	88	CH₃CH₂SO₂—	H	F	P-111
	x-b		F	F	P-112
	y-b		H	H	P-113
chloromethaneslfonyl	88	ClCH₂SO₂—	H	F	P-114
chloride	x-b		F	F	P-115
	y-b		H	H	P-116
cyanomethanesulfonyl	88	NCCH₂SO₂—	H	F	P-117
chloride	x-b		F	F	P-118
	y-b		H	H	P-119
N-methylsulfamoyl	88	CH₃NHSO₂—	H	F	P-120
chloride	x-b		F	F	P-121
	y-b		H	H	P-122
N,N-dimethylsulfamoyl	88	(CH₃)₂NSO₂—	H	F	P-123
chloride	x-b		F	F	P-124
	y-b		H	H	P-125
ethyl chloroformate	88 x-b y-b		H F H	F F H	P-126 P-127 P-128

sulfamide	88	H₂NSO₂—	H	F	P-129
	x-b		F	F	P-130
	y-b		H	H	P-131
chloroacetonitrile	88	NCCH₂—	H	F	P-132
	x-b		F	F	P-133
	y-b		H	H	P-134
2-fluoroethyl bromide	88	FCH₂CH₂—	H	F	P-135
	x-b		F	F	P-136
	y-b		H	H	P-137
N-formylbenzotriazole	88 x-b y-b		H F H	F F H	P-138 P-139 P-140

EXAMPLES 142-161

When following the general procedures of Example 141, step 7, an appropriate amount of the amine listed below and the dithio compound from Preparation Z listed below are utilized, the respective products designated as Examples 142 to 400 in Table H are obtained.

TABLE H


Example			Dithio
No.	Product	Amine	Compound

142	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-	P-90	Z (a)
	2-oxo-5-oxazolidinyl]methyl]propanethioamide; mp
	161-162° C.; Anal. calcd for C₁₉H₂₅FN₄O₃S: C, 55.87;
	H, 6.17; N, 13.72; S, 7.85. Found: C, 55.79; H, 6.26;
	N, 13.60; S, 7.71
143	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-	P-90	Z (b)
	2-oxo-5-oxazolidinyl]methyl]-2-methylpropane-
	thioamide
144	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-	P-90	Z (c)
	2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbo-
	thioamide; mp 159-160° C.; Anal. calcd for
	C₂₀H₂₅FN₄O₃S: C, 57.13; H, 5.99; N, 13.32; S, 7.62.
	Found: C, 57.05; H, 6.01; N, 13.15; S, 7.45.
145	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-	P-90	Z (d)
	2-oxo-5-oxazolidinyl]methyl]butanethioamide
146	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-	P-90	Z (e)
	2-oxo-5-oxazolidinyl]methyl]-3-methylbutane-
	thioamide
147	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-	P-90	Z (f)
	2-oxo-5-oxazolidinyl]methyl]-2-methylbutane-
	thioamide
148	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-	P-90	Z (g)
	2-oxo-5-oxazolidinyl]methy;]-3,3-dimethylbutane-
	thioamide
149	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-	P-90	Z (h)
	2-oxo-5-oxazolidinyl]methyl]cyclobutanecarbo-
	thioamide
150	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-	P-90	Z (i)
	2-oxo-5-oxazolidinyl]methyl]cyclopentanecarbo-
	thioamide
151	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-	P-90	Z (j)
	2-oxo-5-oxazolidinyl]methyl]cyclohexanecarbo-
	thioamide
152	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-	P-90	Z (k)
	2-oxo-5-oxazolidinyl]methy;]-2-cyclopropylethane-
	thioamide
153	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-	P-90	Z (l)
	2-oxo-5-oxazolidinyl]methyl]-2-cyclobutylethane-
	thioamide
154	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-	P-90	Z (m)
	2-oxo-5-oxazolidinyl]methyl]-2-cyclopentylethane-
	thioamide
155	(S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1-piperazinyl)-	P-91	Ethyl
	phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide		dithio-
			acetate
156	(S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1-piperazinyl)-	P-91	Z (a)
	phenyl]-2-oxo-5-oxazolidinyl]methyl]propane-
	thioamide
157	(S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1-piperazinyl)-	P-91	Z (b)
	phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methyl-
	propanethioamide
158	(S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1-piperazinyl)-	P-91	Z (c)
	pjhenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane-
	carbothioamide
159	(S)-N-[[3-[4-(4-Acetyl-1-piperazinyl)phenyl]-2-oxo-5-	P-92	Ethyl
	oxazolidinyl]methyl]thioacetamide		dithio-
			acetate
160	(S)-N-[[3-[4-(4-Acetyl-1-piperazinyl)phenyl]-2-oxo-5-	P-92	Z (a)
	oxazolidinyl]methyl]propanethioamide
161	(S)-N-[[3-[4-(4-Acetyl-1-piperazinyl)phenyl]-2-oxo-5-	P-92	Z (b)
	oxazolidinyl]methyl]-2-methylpropanethioamide
162	(S)-N-[[3-[4-(4-Acetyl-1-piperazinyl)phenyl]-2-oxo-5-	P-92	Z (c)
	oxazolidinyl]methyl]cyclopropanecarbothioamide
163	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
164	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
165	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
166	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothiamide
167	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	Z (d)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	butanethioamide
168	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	Z (e)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3-
	methylbutanethioamide
169	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	Z (f)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylbutanethioamide
170	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	Z (g)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-
	dimethylbutanethioamide
171	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	Z (h)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclobutanecarbothioamide
172	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	Z (i)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopentanecarbothioamide
173	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	Z (j)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclohexanecarbothioamide
174	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	Z (k)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	cyclopropylethanethioamide
175	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	Z (l)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	cyclobutylethanethioamide
176	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	Z (m)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	cyclopentylethanethioamide
177	(S)-N-[[3-[3,5-Difluoro-[4-[4-(methoxyacetyl)-1-	P-94	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
178	(S)-N-[[3-[3,5-Dilfuooro[4-[4-(methoxyacetyl)-1-	P-94	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
179	(S)-N-[[3-[3,5-Difluoro-[4-[4-(methoxyacetyl)-1-	P-94	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
180	(S)-N-[[3-[3,5-Difluoro[4-[4-(methoxyacetyl)-1-	P-94	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
181	(S)-N-[[3-[4-[4-(methoxyacetyl)-1-piperazinyl]phenyl]-	P-95	Ethyl
	2-oxo-5-oxazolidinyl]methyl]thioacetamide
182	(S)-N-[[3-[4-[4-(methoxyacetyl)-1-piperazinyl]phenyl]-	P-95	Z (a)
	2-oxo-5-oxazolidinyl]methyl]propanethioamide
183	(S)-N-[[3-[4-[4-(methoxyacetyl)-1-piperazinyl]phenyl]-	P-95	Z (b)
	2-oxo-5-oxazolidinyl]methyl]-2-methylpropane-
	thioamide
184	(S)-N-[[3-[4-[4-(methoxyacetyl)-1-piperazinyl]phenyl]-	P-95	Z (c)
	2-oxo-5-
	oxazolidinyl]methyl]cyclopropanecarbothioamide
185	(S)-N-[[3-[3-Fluoro-4-[4-(cyanoacetyl)-1-piperazinyl]-	P-96	Ethyl
	phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide		dithio-
			acetate
186	(S)-N-[[3-[3-Fluoro-4-[4-(cyanoacetyl)-1-piperazinyl]-	P-96	Z (a)
	phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethio-
	amide
187	(S)-N-[[3-[3-Fluoro-4-[4-(cyanoacetyl)-1-piperazinyl]-	P-96	Z (b)
	phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methyl-
	propanethioamide
188	(S)-N-[[3-[3-Fluoro-4-[4-(cyanoacetyl)-1-piperazinyl]-	P-96	Z (c)
	phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane-
	carbothiamide
189	(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanoacetyl)-1-	P-97	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-		dithio-
	methyl]thioacetamide		acetate
190	(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanoacetyl)-1-	P-97	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]propanethioamide
191	(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanoacetyl)-1-	P-97	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
192	(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanoacetyl)-1-	P-97	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]cyclopropanecarbothioamide
193	(S)-N-[[3-[4-[4-(Cyanoacetyl)-1-piperazinyl]phenyl]-2-	P-98	Ethyl
	oxo-5-oxazolidinyl]methyl]thioacetamide		dithio-
			acetate
194	(S)-N-[[3-[4-[4-(Cyanoacetyl)-1-piperazinyl]phenyl]-2-	P-98	Z (a)
	oxo-5-oxazolidinyl]methyl]propanethioamide
195	(S)-N-[[3-[4-[4-(Cyanoacetyl)-1-piperazinyl]phenyl]-2-	P-98	Z (b)
	oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide
196	(S)-N-[[3-[4-[4-(Cyanoacetyl)-1-piperazinyl]phenyl]-2-	P-98	Z (c)
	oxo-5-oxazolidinyl]methyl]cyclopropanecarbothio-
	amide
197	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	thioacetamide
198	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
199	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
200	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
201	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	Z (d)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	butanethioamide
202	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	Z (e)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3-
	methylbutanethioamide
203	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	Z (f)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylbutanethioamide
204	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	Z (g)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-
	dimethylbutanethioamide
205	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	Z (h)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclobutanecarbothioamide
206	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	Z (i)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopentanecarbothioamide
207	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	Z (j)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclohexanecarbothioamide
208	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	Z (k)
	piperazinyl]phenyl]-2-oxo-5-oxazlidinyl]methyl]-2-
	cyclopropylethanethioamide
209	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	Z (l)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	cyclobutylethanethioamide
210	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	Z (m)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	cyclopentylethanethioamide
211	(S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxyacetyl)-1-	P-100	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	thioacetamide
212	(S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxyacetyl)-1-	P-100	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
213	(S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxyacetyl)-1-	P-100	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
214	(S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxyacetyl)-1-	P-100	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
215	(S)-N-[[3-[4-[4-(Acetoxyacetyl)-1-piperazinyl]phenyl]-	P-101	Ethyl
	2-oxo-5-oxazolidinyl]methyl]thioacetamide		dithio-
			acetate
216	(S)-N-[[3-[4-[4-(Acetoxyacetyl)-1-piperazinyl]phenyl]-	P-101	Z (a)
	2-oxo-5-oxazolidinyl]methyl]propanethioamide
217	(S)-N-[[3-[4-[4-(Acetoxyacetyl)-1-piperazinyl]phenyl]-	P-101	Z (b)
	2-oxo-5-oxazolidinyl]methyl]-2-methylpropane-
	thioamide
218	(S)-N-[[3-[4-[4-(Acetoxyacetyl)-1-piperazinyl]phenyl]-	P-101	Z (c)
	2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbo-
	thioamide
219	(S)-N-[[3-[3-Fluoro-4-[4-(benzyloxyacetyl)-1-	P-102	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
220	(S)-N-[[3-[3-Fluoro-4-[4-(benzyloxyacetyl)-1-	P-102	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
221	(S)-N-[[3-[3-Fluoro-4-[4-(benzyloxyacetyl)-1-	P-102	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanecarbothioamide
222	(S)-N-[[3-[3-Fluoro-4-[4-(benzyloxyacetyl)-1-	P-102	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
223	(S)-N-[[3-[3,5-Difluoro-4-[4-(benzyloxyacetyl)-1-	P-103	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
224	(S)-N-[[3-[3,5-Difluoro-4-[4-(benzyloxyacetyl)-1-	P-103	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
225	(S)-N-[[3-[3,5-Difluoro-4-[4-benzyloxyacetyl)-1-	P-103	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
226	(S)-N-[[3-[3,5-Difluoro-4-[4-(benzyloxyacetyl)-1-	P-103	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
227	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-	P-105	Ethyl
	piperazinyl]phenyl]-2-oxo-5-		dithio-
	oxazolidinyl]methyl]thioacetamide		acetate
228	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-	P-105	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
229	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-	P-105	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
230	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-	P-105	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
231	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-	P-105	Z (d)
	piperazinyl]phenyl]-2-oxo-5-oxazlidinyl]methyl]-
	butanethioamide
232	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-	P-105	Z (e)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3-
	methylbutanethioamide
233	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-	P-105	Z (f)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylbutanethioamide
234	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-	P-105	Z (g)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-
	dimethylbutanethioamide
235	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-	P-105	Z (h)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclobutanecarbothioamide
236	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-	P-105	Z (i)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopentanecarbothioamide
237	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-	P-105	Z (j)
	piperazinyl]phenyl]-2-oxo-5-oxaolidinyl]methyl]-
	cyclohexanecarbothioamide
238	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-	P-105	Z (k)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	cyclopropylethanethioamide
239	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-	P-105	Z (l)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	cyclobutylethanethioamide
240	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-	P-105	Z (m)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	cyclopentylethanethioamide
241	(S)-N-[[3-[3,5-Difluoro-4-[4-(methoxycarbonyl)-1-	P-106	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
242	(S)-N-[[3-[3,5-Difluoro-4-[4-(methoxycarbonyl)-1-	P-106	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
243	(S)-N-[[3-[3,5-Difluoro-4-[4-(methoxycarbonyl)-1-	P-106	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxaolidinyl]methyl]-2-
	methylpropanethioamide
244	(S)-N-[[3-[3,5-Difluoro-4-[4-(methoxycarbonyl)-1-	P-106	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
245	(S)-N-[[3-[4-[4-(methoxycarbonyl)-1-	P-107	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
246	(S)-N-[[3-[4-[4-(methoxycarbonyl)-1-	P-107	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
247	(S)-N-[[3-[4-[4-(methoxycarbonyl)-1-	P-107	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
248	(S)-N-[[3-[4-[4-(methoxycarbonyl)-1-	P-107	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
249	(S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1-	P-108	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide; mp 197-198° C.; Anal. calcd for		acetate
	C₁₇H₂₃FN₄O₄S₂: C, 47.43; H, 5.39; N, 13.01; C, 14.89.
	Found: C, 47.25; H, 5.40; N, 12.82; S, 14.56.
250	(S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1-	P-108	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide; mp 207-208° C.; Anal. calcd for
	C₁₈H₂₅FN₄O₄S₂: C, 48.63; H, 5.67; N, 12.60; S, 14.42.
	Found: C, 48.51; H, 5.59; N, 12.52; S, 14.09.
251	(S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1-	P-108	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide; mp 204-206° C.; Anal. calcd
	for C₁₉H₂₇FN₄O₄S₂: C, 49.76; H, 5.93; N, 12.22; S,
	13.98. Found: C, 49.63; H, 5.92; N, 14.14; S, 13.91.
252	(S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1-	P-108	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide; Anal. calcd for
	C₁₉H₂₅FN₄O₄S₂: C, 49.98; H, 5.52; N, 12.27; S, 14.04.
	Found: C, 49.42; H, 5.50; N, 12.08; S, 13.80.
253	(S)-N-[[3-[3,5-Difluoro-4-[4-(methanesulfonyl)-1-	P-109	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
254	(S)-N-[[3-[3,5-Difluoro-4-[4-(methanesulfonyl)-1-	P-109	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
255	(S)-N-[[3-[3,5-Difluoro-4-[4-(methanesulfonyl)-1-	P-109	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
256	(S)-N-[[3-[3,5-Difluoro-4-[4-(methanesulfonyl)-1-	P-109	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
257	(S)-N-[[3-[4-[4-(methanesulfonyl)-1-	P-110	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide
258	(S)-N-[[3-[4-[4-(methanesulfonyl)-1-	P-110	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
259	(S)-N-[[3-[4-[4-(methanesulfonyl)-1-	P-110	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
260	(S)-N-[[3-[4-[4-(methanesulfonyl)-1-	P-110	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
261	(S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)-1-	P-111	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
262	(S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)-1-	P-111	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
263	(S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)-1-	P-111	Z (b)
	piperazinyl]phenyl]-2-oxo-5-exazolidinyl]methyl]-2-
	methylpropanethioamide
264	(S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)-1-	P-111	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopeopanecarbothioamide
265	(S)-N-[[3-[3,5-Difluoro-4-[4-(ethanesulfonyl)-1-	P-112	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
266	(S)-N-[[3-[3,5-Difluoro-4-[4-(ethanesulfonyl)-1-	P-112	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
267	(S)-N-[[3-[3,5-Difluoro-4-[4-(ethanesulfonyl)-1-	P-112	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
268	(S)-N-[[3-[3,5-Difluoro-4-[4-(ethanesulfonyl)-1-	P-112	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
269	(S)-N-[[3-[4-[4-(ethanesulfonyl)-1-piperazinyl]phenyl]-	P-113	Ethyl
	2-oxo-5-oxazolifinyl]methyl]thioacetamide		dithio-
			acetate
270	(S)-N-[[3-[4-[4-(ethanesulfonyl)-1-piperazinyl]phenyl]-	P-113	Z (a)
	2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide
271	(S)-N-[[3-[4-[4-(ethanesulfonyl)-1-piperazinyl]phenyl]-	P-113	Z (b)
	2-oxo-5-oxazolidinyl]methyl]-2-methylpropane-
	thioamide
272	(S)-N-[[3-[4-[4-(ethanesulfonyl)-1-piperazinyl]phenyl]-	P-113	Z (c)
	2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothio-
	amide
273	(S)-N-[[3-[3-Fluoro-4-[4-(chloromethanesulfonyl)-1-	P-114	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
274	(S)-N-[[3-[3-Fluoro-4-[4-(chloromethanesulfonyl)-1-	P-114	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
275	(S)-N-[[3-[3-Fluoro-4-[4-(chloromethanesulfonyl)-1-	P-114	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
276	(S)-N-[[3-[3-Fluoro-4-[4-(chloromethanesulfonyl)-1-	P-114	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
277	(S)-N-[[3-[3,5-Difluoro-4-[4-(chloromethanesulfonyl)-	P-115	Ethyl
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
278	(S)-N-[[3-[3,5-Difluoro-4-[4-(chloromethanesulfonyl)-	P-115	Z (a)
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
279	(S)-N-[[3-[3,5-Difluoro-4-[4-(chloromethanesulfonyl)-	P-115	Z (b)
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
280	(S)-N-[[3-[3,5-Difluoro-4-[4-(chloromethanesulfonyl)-	P-115	Z (c)
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
281	(S)-N-[[3-[4-[4-(chloromethanesulfonyl)-1-	P-116	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide
282	(S)-N-[[3-[4-[4-(chloromethanesulfonyl)-1-	P-116	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
283	(S)-N-[[3-[4-[4-(chloromethanesulfonyl)-1-	P-116	Z (b)
	piperazinyl]phenyl]-2-oxo-5-pxazolidinyl]methyl]-2-
	methylpropanethioamide
284	(S)-N-[[3-[4-[4-(chloromethanesulfonyl)-1-	P-116	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
285	(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane-sulfonyl)-1-	P-117	Ethyl
	piperazinyl]phenyl]-2-oxo-5-		dithio-
	oxazolidinyl]methyl]thioacetamide		acetate
286	(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane-sulfonyl)-1-	P-117	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
287	(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane-sulfonyl)-1-	P-117	Z (b)
	piperazinyl]phenyl]020oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
288	(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane-sulfonyl)-1-	P-117	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
289	(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethane-sulfonyl)-	P-118	Ethyl
	1-piperazinyl]phenyl]-2-oxo-5-		dithio-
	oxazolidinyl]methyl]thioacetamide		acetate
290	(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethane-sulfonyl)-	P-118	Z (a)
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]propanethioamide
291	(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethane-sulfonyl)-	P-118	Z (b)
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
292	(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethane-sulfonyl)-	P-118	Z (c)
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
293	(S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)-1-	P-119	Ethyl
	piperazinyl]phenyl]-2-oxo-5-		dithio-
	oxazolidinyl]methyl]thioacetamide		acetate
294	(S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)-1-	P-119	Z (a)
	piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]propanethioamide
295	(S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)-1-	P-119	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
296	(S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)-1-	P-119	Z (c)
	piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]cyclopropanecarbothioamide
297	(S)-N-[[3-[3-Fluoro-4-[4-(N-methylsulfomaoyl)-1-	P-120	Ethyl
	piperazinyl]phenyl]-2-oxo-5-		dithio-
	oxazolidinyl]methyl]thioacetamide		acetate
298	(S)-N-[[3-[3-Fluoro-4-[4-(N-methylsulfamoyl)-1-	P-120	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
299	(S)-N-[[3-[3-Fluoro-4-[4-(N-methylsulfamoyl)-1-	P-120	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
300	(S)-N-[[3-[3-Fluoro-4-[4-(N-methylsulfamoyl)-1-	P-120	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
301	(S)-N-[[3-[3,5-Difluoro-4-[4-(N-methylsulfamoyl)-1-	P-121	Ethyl
	piperazinyl]phenyl]-2-oxo-5-		dithio-
	oxazolidinyl]methyl]thioacetamide		acetate
302	(S)-N-[[3-[3,5-Difluoro-4-[4-(N-methylsulfamoyl)-1-	P-121	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
303	(S)-N-[[3-[3,5-Difluoro-4-[4-(N-methylsulfamoyl)-1-	P-121	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
304	(S)-N-[[3-[3,5-Difluoro-4-[4-(N-methylsulfamoyl)-1-	P-121	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
305	(S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1-	P-122	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
306	(S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1-	P-122	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
307	(S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1-	P-122	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
308	(S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1-	P-122	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
309	(S)-N-[[3-[30Fluoro-4-[4-(N,N-dimethylsulfamoyl)-1-	P-123	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
310	(S)-N-[[3-[3-Fluoro-4-[4-(N,N-dimethylsulfamoyl)-1-	P-123	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
311	(S)-N-[[3-[3-Fluoro-4-[4-(N,N-dimethylsulfamoyl)-1-	P-123	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
312	(S)-N-[[3-[3-Fluoro-4-[4-(N,N-dimethylsulfamoyl)-1-	P-123	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
313	(S)-N-[[3-[3,5-Difluoro-4-[4-(N,N-dimethylsulfamoyl)-	P-124	Ethyl
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide
314	(S)-N-[[3-[3,5-Difluoro-4-[4-(N,Ndimethylsulfamoyl)-	P-124	Z (a)
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
315	(S)-N-[[3-[3,5-Difluoro-4-[4-(N,N-dimethylsulfamoyl)-	P-124	Z (b)
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
316	(S)-N-[[3-[3,5-Difluoro-4-[4-(N,N-dimethylsulfamoyl)-	P-124	Z (c)
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
317	(S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)-1-	P-125	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
318	(S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)-1-	P-125	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
319	(S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)-1-	P-125	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
320	(S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)-1-	P-125	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
321	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	thioacetamide
322	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
323	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
324	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
325	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	Z (d)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	butanethioamide
326	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	Z (e)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3-
	methylbutanethioamide
327	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	Z (f)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylbutanethioamide
328	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	Z (g)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-
	dimethylbutanethioamide
329	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	Z (h)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclobutanecarbothioamide
330	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	Z (i)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopentanecarbothioamide
331	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	Z (j)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclohexanecarboamide
332	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	Z (k)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropylethanethioamide
333	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	Z (l)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	cyclobutylethanthioamide
334	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	Z (m)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	cyclopentylethanethioamide
335	(S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxycarbonyl)-1-	P-127	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide
336	(S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxycarbonyl)-1-	P-127	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
337	(S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxycarbonyl)-1-	P-127	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
338	(S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxycarbonyl)-1-	P-127	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
339	(S)-N-[[3-[4-[4-(ethoxycarbonyl)-1-piperazinyl]-	P-128	Ethyl
	phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide		dithio-
			acetate
340	(S)-N-[[3-[4-[4-(ethoxycarbonyl)-1-piperazinyl]-	P-128	Z (a)
	phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
341	(S)-N-[[3-[4-[4-(ethoxycarbonyl)-1-piperazinyl]-	P-128	Z (b)
	phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
342	(S)-N-[[3-[4-[4-(ethoxycarbonyl)-1-piperazinyl]-	P-128	Z (c)
	phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane-
	carbothioamide
343	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-piperazinyl)-	P-129	Ethyl
	phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide		dithio-
			acetate
344	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-piperazinyl)-	P-129	Z (a)
	phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
345	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-piperazinyl)-	P-129	Z (b)
	phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
346	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-piperazinyl)-	P-129	Z (c)
	phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
347	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	Z (d)
	piperazinyl)phenyl]-2-oxo-5-
	oxazolidinyl]methyl]butanethioamide
348	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	Z (e)
	piper4azinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-3-
	methylbutanethioamide
349	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	Z (f)
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylbutanethioamide
350	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	Z (g)
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-
	dimethylbutanethioamide
351	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	Z (h)
	piperazinyl)phenyl]-2-oxo-5-
	oxazolidinyl]methyl]cyclobutanecarbothioamide
352	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	Z (h)
	piperazinyl)phenyl]-2-oxo-5-
	oxazolidinyl]methyl]cyclopentanecarbothioamide
353	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	Z (j)
	piperazinyl)phenyl]-2-oxo-5-
	oxazolidinyl]methyl]cyclohexanecarbothioamide
354	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	Z (k)
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	cyclopropylethanethioamide
355	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	Z (l)
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
356	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	Z (m)
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	cyclopentylethanethioamide
357	(S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1-	P-130	Ethyl
	piperazinyl)phenyl]-2-oxo-5-		dithio-
	oxazolidinyl]methyl]thioacetamide		acetate
358	(S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1-	P-130	Z (a)
	piperazinyl)phenyl]-2-oxo-5-
	oxazolidinyl]methyl]propanethioamide
359	(S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1-	P-130	Z (b)
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
360	(S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1-	P-130	Z (c)
	piperazinyl)phenyl]-2-oxo-5-
	oxazolidinyl]methyl]cyclopropanecarbothioamide
361	(S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)phenyl]-2-oxo-	P-131	Ethyl
	5-oxazolidinyl]methyl]thioacetamide		dithio-
			acetate
362	(S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)phenyl]-2-oxo-	P-131	Z (a)
	5-oxazolidinyl]methyl]propanethioamide
363	(S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)phenyl]-2-oxo-	P-131	Z (b)
	5-oxazolidinyl]methyl]-2-methylpropanethioamide
364	(S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)phenyl]-2-oxo-	P-131	Z (c)
	5-oxazolidinyl]methyl]cyclopropanecarbothioamide
365	(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1-	P-132	Ethyl
	piperazinyl]phenyl]-2-oxo-5-		dithio-
	oxazolidinyl]methyl]thioacetamide
366	(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1-	P-132	Z (a)
	piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]propanethioamide
367	(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1-	P-132	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
368	(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1-	P-132	Z (c)
	piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]cyclopropanecarbothioamide
369	(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethyl)-1-	P-133	Ethyl
	piperazinyl]phenyl]-2-oxo-5-		dithio-
	oxazolidinyl]methyl]thioacetamide		acetate
370	(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethyl)-1-	P-133	Z (a)
	piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]propanethioamide
371	(S)-N-[[3-[3,5-Difluoro-4-[4 cyanomethyl)-1-	P-133	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
372	(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethyl)-1-	P-133	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
373	(S)-N-[[3-[4-[4-(cyanomethyl)-1-piperazinyl]phenyl]-2-	P-134	Ethyl
	oxo-5-oxazolidinyl]methyl]thioacetamide		dithio-
			acetate
374	(S)-N-[[3-[4-[4-(cyanomethyl)-1-piperazinyl]phenyl]-2-	P-134	Z (a)
	oxo-5-oxazolidinyl]methyl]propanethioamide
375	(S)-N-[[3-[4-[4-(cyanomethyl)-1-piperazinyl]phenyl]-2-	P-134	Z (b)
	oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide
376	(S)-N-[[3-[4-[4-(cyanomethyl)-1-piperazinyl]phenyl]-	P-134	Z (c)
	2-oxo-5-oxazolidinyl]methyl]cyclopropane-
	carbothioamide
377	(S)-N-[[3-[3-Fluoro-4-[3-(2-fluoroethyl)-1-	P-135	Ethyl
	piperazinyl]phenyl]-2-oxo-5-		dithio-
	oxazolidinyl]methyl]thioacetamide		acetate
378	(S)-N-[[3-[3-Fluoro-4-[4-(2-fluoroethyl)-1-	P-135	Z (a)
	piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]propanethioamide
379	(S)-N-[[3-[3-Fluoro-4-[4-(2-fluoroethyl)-1-	P-135	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
380	(S)-N-[[3-[3-Fluoro-4-[43-(2-fluoroethyl)-1-	P-135	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
381	(S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoroethyl)-1-	P-136	Ethyl
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-		dithio-
	thioacetamide		acetate
382	(S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoroethyl)-1-	P-136	Z (a)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
383	(S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoroethyl)-1-	P-136	Z (b)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
384	(S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoroethyl)-1-	P-136	Z (c)
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	cyclopropanecarbothioamide
385	(S)-N-[[3-[4-[4-(2-fluoroethyl)-1-piperazinyl]phenyl]-	P-137	Ethyl
	2-oxo-5-oxazolidinyl]methyl]thioacetamide		dithio-
			acetate
386	(S)-N-[[3-[4-[4-(2-fluoroethyl)-1-piperazinyl]phenyl]-	P-137	Z (a)
	2-oxo-5-oxazolidinyl]methyl]propanethioamide
387	(S)-N-[[3-[4-[4-(2-fluoroethyl)-1-piperazinyl]phenyl]-	P-137	Z (b)
	2-oxo-5-oxazolidinyl]methyl]-2-
	methylpropanethioamide
388	(S)-N-[[3-[4-[4-(2-fluoroethyl)-1-piperazinyl]phenyl]-	P-137	Z (c)
	2-oxo-5-oxazolidinyl]methyl]cyclopropane-
	carbothioamide
389	(S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]-	P-138	Ethyl
	2-oxo-5-oxazolidinyl]methyl]thioacetamide; Ana calcd		dithio-
	for C₁₇H₂₁FN₄O₃S: C, 53.67; H, 5.56; N, 14.73; S,		acetate
	8.43. Found: C, 53.14; H, 5.42; N, 14.25; S, 8.18.
390	(S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]-	P-138	Z (a)
	2-oxo-5-oxazolidinyl]methyl]propanethioamide; mp
	166-167° C.; Anal. calcd for C₁₈H₂₃FN₄O₃S: C, 54.81;
	H, 5.88; N, 14.20; S, 8.13. Found: C, 54.83; H, 6.00;
	N, 14.12; S, 7.96.
391	(S)-N-[[3-[3-Fluoro-4-(4-formyla-1-piperazinyl)phenyl]-	P-138	Z (b)
	2-oxo-5-oxazolidinyl]methyl]-2-methylpropane-
	thioamide; mp 157-158° C.: Anal. calcd for
	C₁₉H₂₅FN₄O₃S: C, 55.87, H, 6.17; N, 13.72; S, 7.85.
	Found: C, 55.67; H, 6.19; N, 13.50; S, 7.70.
392	(S)-N-[[3-Fluoro-4-(4-formyla-1-piperazinyl)phenyl]-	P-138	Z (c)
	2-oxo-5-oxazolidinyl]methyl]cyclopropane-
	carbothioamide; mp 178-179° C.; Anal. calcd for
	C₁₉H₂₃FN₄O₃S: C, 56.14; H, 5.70; N, 13.78; S, 7.89.
	Found: C, 56.13; H, 5.64; N, 13.64; S, 7.75.
393	(S)-N-[[3-[3,5-Difluoro-4-(4-formyl-1-piperazinyl)-	P-139	Ethyl
	phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide		dithio-
			acetate
394	(S)-N-[[3-[3,5-Difluoro-4-(4-formyl-1-piperazinyl)-	P-139	Z (a)
	phenyl]-2-oxo-5-oxazolidinyl]methyl]-
	propanethioamide
395	(S)-N-[[3-[3,5-Difluoro-4-(4-formyla-1-piperazinyl)-	P-139	Z (b)
	phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methyl-
	propanethioamide
396	(S)-N-[[3-[3,5-Difluoro-4-(4-formyla-1-piperazinyl)-	P-139	Z (c)
	phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclo-
	propanecarbothioamide
397	(S)-N-[[3-[4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5-	P-140	Ethyl
	oxazolidinyl]methyl]thioacetamide		dithio-
			acetate
398	(S)-N-[[3-[4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5-	P-140	Z (a)
	oxazolidinyl]methyl]propanethioamide
399	(S)-N-[[3-[4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5-	P-140	Z (b)
	oxazolidinyl]methyl]-2-methylpropanethioamide
400	(S)-N-[[3-[4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5-	P-140	Z (c)
	oxazolinyl]methyl]cyclopropane-carbothiamide

When in the general procedure of Example 31, step 1, an appropriate amount of the amine listed below is substituted for compound [0874] 33, the isothiocyanate corresponding to the amines P-90, P-93, P-99, P-105, P-126 and P-129 are obtained.

When in the general procedure of Example 114 an appropriate amount of the isothiocyanate and the amine listed below are substituted for compound 82 and methylamine, the respective products listed below are obtained.

TABLE I


		Isothiocyanate
Example		Corresponding
No.	Product	to Amine No.	Amine

401	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-	P-90	methylamine
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-N′-methylthiourea
402	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-	P-90	dimethylamine
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-N′,N′-dimethylthiourea
403	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-	P-90	azetidine
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-1-azetidinecarbothioamide
404	(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)-	P-90	anhydrous
	phenyl]-2-oxo-5-oxazolidinyl]methyl]-		ammonia
	thiourea
405	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	methylamine
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-N′-methylthiourea
406	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	dimethylamine
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-N′,N′-dimethylthiourea
407	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-	P-93	azetidine
	piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-1-
	azetidinecarbothioamide
408	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	methylamine
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-N′-methylthiourea
409	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	dimethylamine
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-N′,N′-dimethylthiourea
410	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-	P-99	azetidine
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-1-azetidinecarbothioamide
411	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-	P-105	methylamine
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-N′-methylthiourea
412	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-	P-105	dimethylamine
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-N′,N′-dimethylthiourea
413	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-	P-105	azetidine
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-1-azetidinecarbothioamide
414	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	methylamine
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-N′-methylthiourea
415	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	dimethylamine
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-N′,N′-dimethylthiourea
416	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-	P-126	azetidine
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-1-azetidinecarbothioamide
417	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	methylamine
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-N′-methylthiourea
418	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	dimethylamine
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-N′,N′-dimethylthiourea
419	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	azetidine
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-1-azetidinecarbothioamide

When in the general procedure of Example 100 an appropriate amount of the isothiocyanate and alcohol listed below are utilized in the same manner as Compound 82 and methanol are utilized, the respective products listed below are obtained.

TABLE J


		Isothio-
		cyanate
Ex-		Corres-
am-		ponding to
ple		Amine
No.	Product	No.	Amine

420	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-	P-90	methanol
	piperazinyl)phenyl]2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
421	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-	P-90	ethanol
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-ethylthiocarbamate
422	(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-	P-90	isopropyl
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-		alcohol
	methyl]-O-iso-propylthiocarbamate
423	(S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1-	P-91	methanol
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
424	(S)-N-[[3-[4-(4-Acetyl-1-	P-92	methanol
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
425	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-	P-93	methanol
	1-piperazinyl]phenyl]-2-oxo-5-oxazoli-
	dinyl]-methyl]-O-methylthiocarbamate
426	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-	P-93	ethanol
	1-piperazinyl]phenyl]-2-oxo-5-oxazoli-
	dinyl]methyl]-O-ethylthiocarbamate
427	(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-	P-93	isopropyl
	1-piperazinyl]phenyl]-2-oxo-5-		alcohol
	oxazolidinyl]-methyl]-O-iso-
	propylthiocarbamate
428	(S)-N-[[3-[3,5-Difluoro-[4-[4-(methoxy-	P-94	methyl-
	acetyl)-1-piperazinyl]phenyl]-2-oxo-5-		aminel
	oxazolidinyl]methyl]-O-methylthio-
	carbamate
429	(S)-N-[[3-[4-[4-(methoxyacetyl)-1-	P-95	methyl-
	piperazinyl]phenyl]-2-oxo-5-		amine
	oxazolidinyl]methyl]-O-methylthio-
	carbamate
430	(S)-N-[3-[3-Fluoro-4-[4-(cyanoacetyl)-1-	P-96	methanol
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
431	(S)-N-[[3-[3,5-Difluoro-4-[4-(cyano-	P-97	methanol
	acetyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]-methyl]-O-methylthio-
	carbamate
432	(S)-N-[[3-[4-[4-(Cyanoacetyl)-1-	P-98	methanol
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
433	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-	P-99	methanol
	1-piperazinyl]phenyl]-2-oxo-5-oxazoli-
	dinyl]-methyl]-O-methylthiocarbamate
434	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-	P-99	ethanol
	1-piperazinyl]phenyl]-2-oxo-5-oxazoli-
	dinyl]-methyl]-O-ethylthiocarbamate
435	(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-	P-99	isopropyl
	1-piperazinyl]phenyl]-2-oxo-5-oxazoli-		alcohol
	dinyl]-methyl]-O-iso-propylthiocarbamate
436	(S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxy-	P-100	methanol
	acetyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]-methyl]-O-methylthio-
	carbamate
437	(S)-N-[[3-[4-[4-(Acetoxyacetyl)-1-	P-101	methanol
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
438	(S)-N-[[3-[3-Fluoro-4-[4-(benzyloxy-	P-102	methanol
	acetyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]-methyl]-O-methylthio-
	carbamate
439	(S)-N-[[3-[3,5-Difluoro-4-[4-(benzyloxy-	P-103	methanol
	acetyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-O-methylthio-
	carbamate
440	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycar-	P-105	methanol
	bonyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]-methyl]-O-methylthio-
	carbamate
441	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycar-	P-105	ethanol
	bonyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]-methyl]-O-ethylthio-
	carbamate
442	(S)-N-[[3-[3-Fluoro-4-[4-(methoxycar-	P-105	isopropyl
	bonyl)-1-piperazinyl]phenyl]-2-oxo-5-		alcohol
	oxazolidinyl]-methyl]-O-iso-propylthio-
	carbamate
443	(S)-N-[[3-[3,5-Difluoro-4-[4-(methoxy-	P-106	methanol
	carbonyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-O-methylthio-
	carbamate
444	(S)-N-[[3-[4-[4-(methoxycarbonyl)-1-	P-107	methanol
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
445	(S)-N-[[3-[3-Fluoro-4-[4-(methanesul-	P-108	methanol
	fonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxa-
	zolidinyl]-methyl]-O-methylthiocarbamate
446	(S)-N-[[3-[3,5-Difluoro-4-[4-(methane-	P-109	methanol
	sulfonyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-O-methylthio-
	carbamate
447	(S)-N-[[3-[4-[4-(methanesulfonyl)-1-	P-110	methanol
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
448	(S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)-	P-111	methanol
	1-piperazinyl]phenyl]-2-oxo-5-oxazoli-
	dinyl]-methyl]-O-methylthiocarbamate
449	(S)-N-[[3-[3,5-Difluoro-4-[4-(ethane-	P-112	methanol
	sulfonyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]cyclopropane-
	carbothioamide
450	(S)-N-[[3-[4-[4-(ethanesulfonyl)-1-	P-113	methanol
	piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-O-methylthio-
	carbamate
451	(S)-N-[[3-[3-Fluoro-4-[4-(chloromethane-	P-114	methanol
	sulfonyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-O-methylthio-
	carbamate
452	(S)-N-[[3-[3,5-Difluoro-4-[4-(chloro-	P-115	methanol
	methanesulfonyl)-1-piperazinyl]phenyl]-2-
	oxo-5-oxazolidinyl]methyl]-O-methyl-
	thiocarbamate
453	(S)-N-[[3-[4-[4-(chloromethanesulfonyl)-	P-116	methanol
	1-piperazinyl]phenyl]-2-oxo-5-oxazolidi-
	nyl]methyl]-O-methylthiocarbamate
454	(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane-	P-117	methanol
	sulfonyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-O-methylthio-
	carbamate
455	(S)-N-[[3-[3,5-Difluoro-4-[4-(cyano-	P-118	methanol
	methane-sulfonyl)-1-piperazinyl]phenyl]-
	2-oxo-5-oxazolidinyl]methyl]-O-
	methylthiocarbamate
456	(S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)-	P-119	methanol
	1-piperazinyl]phenyl]-2-oxo-5-oxazoli-
	dinyl]-methyl]-O-methylthiocarbamate
457	(S)-N-[[3-[3-Fluoro-4-[4-(N-methyl-	P-120	methanol
	sulfamoyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-O-methylthio-
	carbamate
458	(S)-N-[[3-[3,5-Difluoro-4-[4-(N-methyl-	P-121	methanol
	sulfamoyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-O-methylthio-
	carbamate
459	(S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1-	P-122	methanol
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
460	(S)-N-[[3-[3-Fluoro-4-[4-(N,N-dimethyl-	P-123	methanol
	sulfamoyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-O-methylthio-
	carbamate
461	(S)-N-[[3-[3,5-Difluoro-4-[4-(N,N-di-	P-124	methanol
	methyl-sulfamoyl)-1-piperazinyl]phenyl]-
	2-oxo-5-oxazolidinyl]methyl]-O-methyl-
	thiocarbamate
462	(S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)-	P-125	methanol
	1-piperazinyl]phenyl]-2-oxo-5-oxa-
	zolidinyl]methyl]-O-methylthiocarbamate
463	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycar-	P-126	methanol
	bonyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]-methyl]-O-methylthio-
	carbamate
464	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycar-	P-126	ethanol
	bonyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]-methyl]-O-ethylthio-
	carbamate
465	(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycar-	P-126	isopropyl
	bonyl)-1-piperazinyl]phenyl]-2-oxo-5-		alcohol
	oxazolidinyl]-methyl]-O-iso-propylthio-
	carbamate
466	(S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxy-	P-127	methanol
	carbonyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-O-methylthio-
	carbamate
467	(S)-N-[[3-[4-[4-(ethoxycarbonyl)-1-	P-128	methanol
	piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-O-methylthio-
	carbamate
468	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	methanol
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate,
469	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	ethanol
	piperazinyl)phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-O-ethylthio-
	carbamate
470	(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-	P-129	isopropyl
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-		alcohol
	methyl]-O-iso-propylthiocarbamate
471	(S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1-	P-130	methanol
	piperazinyl)phenyl]-2-oxo-5-
	oxazolidinyl]methyl]-O-methylthio-
	carbamate
472	(S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)-	P-131	methanol
	phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-
	methylthiocarbamate
473	(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1-	P-132	methanol
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
474	(S)-N-[[3-[3,5-Difluoro-4-[4-(cyano-	P-133	methanol
	methyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]-methyl]-O-methylthio-
	carbamate
475	(S)-N-[[3-[4-[4-(cyanomethyl)-1-	P-134	methanoll
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
476	(S)-N-[[3-[3-Fluoro-4-[4-(2-fluoroethyl)-1-	P-135	methanol
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
477	(S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoro-	P-136	methanol
	ethyl)-1-piperazinyl]phenyl]-2-oxo-5-
	oxazolidinyl]-methyl]-O-methylthio-
	carbamate
478	(S)-N-[[3-[4-[4-(2-fluoroethyl)-1-	P-137	methanol
	piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
479	(S)-N-[[3-[3-Fluoro-4-(4-formyl-1-	P-138	methanol
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
480	(S)-N-[[3-[3,5-Difluro-4-(4-formyl-1-	P-139	methanol
	piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-
	methyl]-O-methylthiocarbamate
481	(S)-N-[[3-[4-(4-formyl-1-piperazinyl)-	P-140	methanol
	phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-
	methylthiocarbamate

EXAMPLE 482

(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiazepine S-oxide

[0877]
Step 1. Hexahydro-5-oxo-1,4-thiazepine is prepared according to the procedure described by Gallego ([0878] J. Org. Chem. 1993, 58, 3905-3911).
Step 2. Lithium aluminum hydride (5.5 mL of a 1M solution in THF) is added dropwise to a stirred solution of hexahydro-5-oxo-1,4-thiazepine (721.5 mg) in dry THF (21 mL) cooled to 0° C. The reaction mixture is stirred at 0° C. for 10 min, then at room temperature for 4 h. The reaction mixture is quenched by careful successive addition of water (0.2 mL), 5 N aqueous NaOH (0.2 mL) and water (0.74 mL). The reaction mixture becomes very thick and gel-like. The reaction mixture is diluted with ether (50 mL) and filtered through a pad of celite. The filter cake is washed with ether (100 mL). The filtrate is concentrated to afford 616.6 mg of 1,4-hexahydrothiazepine which is used immediately in the next step. [0879]
Step 3. To a stirred solution of 1,4-hexahydrothiazepine (596.0 mg) and 3,4-difluoronitrobenzene (0.51 mL) in acetonitrile (14 mL) is added diisopropylethylamine (1.0 mL). The yellow solution is heated at reflux for 18 h, then cooled and concentrated. The residue is diluted with CH[0880] ₂Cl₂(100 mL) and washed with saturated aqueous NH₄Cl (35 mL). The phases are separated and the organics are dried (MgSO₄), filtered and concentrated. The residue is purified by flash chromatography using 20% EtOAc in hexane as the eluent to afford 830.2 mg of the nitrobenzene. Mp 115-116° C.; Anal. Calcd for C₁₁H₁₃FN₂O₂S: C, 51.55; H, 5.11; N, 10.93; S, 12.51. Found: C, 51.47; H, 5.12; N, 10.79; S, 12.42.
Step 4. To a stirred suspension of the nitrobenzene prepared in Step 3 (5.5 g) in EtOH (260 mL) is added a solution of 2 M aqueous CuSO[0881] ₄(11.9 mL). The mixture is cooled to 0° C. and NaBH₄(4.1 g) is added in portions. The reaction mixture turns very dark and is stirred at 0° C. for 10 min, at room temperature for 30 min, and then heated at reflux for 3 h. The cooled reaction mixture is diluted with EtOAc (500 ml) and washed with water (200 mL). The aqueous mixture is extracted with EtOAc (3×200 mL). The combined organics are dried (MgSO₄), filtered and concentrated to afford the aniline intermediate.
Step 5. The dark residue from Step 4 is dissolved in 2:1 acetone/water (255 mL) and cooled to 0° C. To this stirred mixture is added solid NaHCO[0882] ₃(5.4 g) followed by benzylchloroformate (7.7 mL). The reaction mixture is stirred at 0° C. for 10 min, then at room temperature for 24 h. The reaction mixture is quenched with 10% aqueous NaHSO₄(200 mL) and then poured into EtOAc (300 mL). The phases are separated and the aqueous phase is extracted with EtOAc (2×250 mL). The combined organics are dried (MgSO₄), filtered and concentrated. The residue is purified by MPLC using 20% EtOAc in hexane to afford 6.03 g of the benzylcarbamate as a yellow solid. mp 72-74° C.; Anal. Calcd for C₁₉H₂₁FN₂O₂S: C, 63.31; H, 5.87; N, 7.77; S, 8.89. Found: C, 63.31; H, 5.97; N, 7.69; S, 8.79.
Step 6. To a stirred solution of the carbamate from Step 5 (3.0 g) in dry THF (33 mL) under N[0883] ₂cooled to 78° C., is added dropwise via syringe a 1.6 M solution of nBuLi in hexane (5.4 mL). The reaction mixture was stirred at 78° C. for 35 min, then R-glycidyl butyrate (1.2 mL) is added. The reaction mixture is stirred at 78° C. for 30 min, then at room temperature overnight during which time a precipitate forms. The reaction mixture is quenched with saturated aqueous NH₄Cl (33 mL) and poured into EtOAc (100 mL). The phases are separated. The organic phase is washed with saturated aqueous NaHCO₃(50 mL), brine (50 mL), dried (MgSO₄), filtered and concentrated. The residue is purified by flash chromatography using EtOAc as the eluent to afford 2.5 g of a hydroxymethyl oxazolidinone. Mp 100-102° C. Anal. Calcd for C₁₅H₁₉FN₂O₃S: C, 55.20; H, 5.87; N, 8.58; S, 9.82. Found: C, 55.09; H, 5.91; N, 8.36; S, 9.57.
Step 7. To a stirred solution of the alcohol prepared in Step 6 (1.7 g) in CH[0884] ₂Cl₂(35 mL) cooled to 0° C., is added triethylamine (1.1 mL) followed by methanesulfonyl chloride (0.5 mL). The reaction mixture is stirred at 0° C. for 10 min, then at room temperature for 1 h. The reaction mixture is treated with water (35 mL). The phases are separated and the aqueous phase is extracted with CH₂Cl₂(35 mL). The combined organic phases are dried (MgSO₄), filtered and concentrated. The residue is purified by flash chromatography using 80% EtOAc in hexane as the eluent to afford 2.1 g of the mesylate. Mp 132-142° C. Anal. Calcd for C₁₆H₂₁FN₂O₅S₂: C, 47.51; H, 5.23; N, 6.93; S, 15.85. Found: C, 47.18; H, 5.28; N, 6.84; S, 15.60.
Step 8. Ammonia gas is bubbled into a stirred suspension of the mesylate prepared in Step 7 (941.7 mg) in 1:1 THF/CH[0885] ₃OH (40 mL) until saturated (approx. 5 min). The reaction mixture is heated in a sealed tube at 100° C. for 72 h. The cooled reaction mixture is concentrated to give the crude amine, which is immediately suspended in CH₂Cl₂(35 mL) and cooled to 0° C. To this stirred suspension is added triethylamine (0.97 mL, 6.9 mmol) followed by di-tert-butyl dicarbonate (759.5 mg, 3.5 mmol). The reaction mixture becomes homogeneous and is stirred at RT for 18 h. The reaction mixture is poured into CH₂Cl₂(75 mL) and washed with H₂O (1×50 mL). The organic phase is dried (MgSO₄), filtered and concentrated. The resulting residue is purified on a Biotage 40 S column using 30-35% ethyl acetate in CH₃OH as the eluent to afford 867.4 mg of the protected amine. mp 74-75° C. Anal Cald: C, 56.45; H, 6.63; N, 9.88. Found: C, 56.95; H, 6.85; N, 9.55.
Step 9. To a stirred suspension of the protected amine prepared in Step 8 (205.2 mg) in 1:1 CH[0886] ₃OH/H₂O (6 mL) cooled to 0° C. is added sodium meta periodate (113.5 mg). The resulting suspension is stirred at RT for 18 h. The reaction mixture is filtered and the solid is washed with CH₂Cl₂(2×20 mL). The filtrate is extracted with H₂O (1×10 mL). The phases are separated. The aqueous phase is extracted with CH₂Cl₂(1×25 mL). The combined organic phases are dried (MgSO₄), filtered and concentrated. The white solid residue is purified on a Biotage 12 M column using 5% CH₃OH in CH₂Cl₂as the eluent to afford 187.3 mg of the sulfoxide. mp 78-81° C.
Step 10. Dry HCl gas is passed over the surface of a stirred solution of the sulfoxide prepared in Step 9 (179.3 mg) in CH[0887] ₃OH (2 mL) cooled to 0° C. for 1 minute. The reaction mixture is stirred at 0° C. for 10 min, then at room temperature for 15 min, then concentrated. The resulting yellow residue is suspended in THF (5 mL) and CH₂Cl₂(5 mL) and cooled to 0° C. To this stirred suspension is added triethylamine (0.46 mL) followed by ethyldithioacetate (0.18 mL). The dark reaction mixture is stirred at RT overnight then concentrated. The dark residue is diluted with CH₂Cl₂(30 mL) and washed with H₂O (2×15 mL). The organic phases are dried (MgSO₄), filtered and concentrated. The dark residue is purified on a Biotage 12 M column using 5% CH₃OH in CH₂Cl₂as the eluent to afford 71.5 mg of the title compound as a tan solid. mp 85-89° C.

Following the general procedure outlined in Step 10 of Example 482, but substituting the dithioesters listed below, the compounds of Examples 483 to 495 of Table K can be obtained.

TABLE K


Example			Dithioester
No.	Compound	Amine	(from Preparation Z)


483	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiazepine S-oxide		Z(a)

484	S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiazepine S- oxide.		Z(b)

485	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiazepine S- oxide.		Z(c)

486	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- butanethioamide, thiazepine S-oxide		Z(d)

487	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide, thiazepine S-oxide		Z(e)

488	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylbutanethioamide, thiazepine S-oxide		Z(f)

489	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide, thiazepine S- oxide		Z(g)

490	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothio- amide, thiazepine S- oxide		Z(h)

491	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- cyclopentanecarbothio- amide, thiazepine S- oxide		Z(i)

492	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclohexanecarbothio- amide, thiazepine S- oxide		Z(j)

493	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethio- amide, thiazepine S- oxide		Z(k)

494	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethio- amide, thiazepine S- oxide		Z(l)

495	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylethanethio- amide, thiazepine S- oxide		Z(m)

EXAMPLE 496

(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiazepine S-oxide

[0889]
The title compound can be prepared by the procedure of Example 482, by substituting an appropriate quantity of 2,6-difluoro-4-nitrobenzene (trifluoromethane) sulfonate for 3,4-difluoronitrobenzene in Step 1. [0890]

Utilizing the amine prepared in Example 496, but substituting the dithioester listed below for ethyl dithioacetate in the final step, the compounds of Examples 497 to 499 of Table L are obtained.

TABLE L


Example			Dithioester
No.	Compound	Amine	(from Preparation Z)


497	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiazepine S-oxide		Z(a)

498	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiazepine S- oxide		Z(b)

499	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiazepine S- oxide		Z(c)

EXAMPLE 500

(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiazepine S-oxide

[0892]
The title compound can be prepared by the procedure of Example 482, by substituting an appropriate quantity of 4-fluoronitrobenzene for 3,4-difluoronitrobenzene in Step 1. [0893]

Utilizing the amine prepared in Example 500, but substituting the dithioester listed below for ethyl dithioacetate in the final step, the compounds of Examples 501 to 503 of Table M are obtained

TABLE M


Example			Dithioester
No.	Compound	Amine	(from Preparation Z)


501	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiazepine S-oxide		Z(a)

502	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiazepine S- oxide		Z(b)

503	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiazepine S- oxide		Z(c)

EXAMPLE 504

(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiazepine S,S-dioxide

[0895]
Step 1. To a stirred solution of the thiazepine prepared in Step 8 of Example 482 (243.7 mg) in 25% H[0896] ₂O/acetone (8 mL) is added 4methylmorpholine N-oxide (201.5 mg) followed by a solution of osmium tetroxide in 2methyl-2-propanol (2.5 wt %, 30 μL). The reaction mixture is stirred at room temperature for 18 h. The reaction mixture is treated with saturated sodium bisulfate (8 mL), then poured into CH₂Cl₂(50 mL). The phases are separated. The aqueous phase is extracted with CH₂Cl₂(2×25 mL). The combined organic phases are washed with brine (1×25 mL), dried (MgSO₄), filtered and concentrated. The residue is purified on a Biotage 40 S column using 1% CH₃OH in CH₂Cl₂as the eluent to afford 216.1 mg (0.47 mmol, 83%) of the thiazepine S,S-dioxide as a white solid. mp 144-146° C.
Step 2. Dry HCl gas is passed over the surface of a stirred solution of the thiazepine S,S-dioxide prepared in Step 1 (108.2 mg) in CH[0897] ₃OH(3 mL) at 0° C. for 1 minute. The reaction mixture is stirred at 0° C. for 10 min and then at room temperature for 15 min. The reaction is concentrated and the yellow residue is suspended in CH₂Cl₂(2 mL) and THF (2 mL). This stirred suspension is cooled to 0° C. and triethylamine (0.27 mL) is added followed by a solution of ethyldithioacetate (0.11 mL) in THF (0.5 mL) with 0.25 mL rinse. The yellowish-green solution is stirred at 0° C. for 10 min then at room temperature for 18 h. The reaction mixture is poured into CH₂Cl₂(20 mL) and washed with H₂O (2×10 mL). The organic phase was dried (MgSO₄), filtered and concentrated. The residue is purified on a Biotage 12 M column using 2% CH₃OH in CH₂Cl₂as the eluent to afford 77.3 mg of the title compound as a white solid. mp 88-90° C.

Following the general procedure outlined in Step 2 of Example 504, but substituting the dithioester listed below for ethyl dithioacetate, the compounds of Examples 505 to 507 of Table N are obtained.

TABLE N


Example			Dithioester
No.	Compound	Amine	(from Preparation Z)


505	(5S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiazepine S,S-dioxide		Z(a)

506	(5S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiazepine S,S- dioxide		Z(b)

507	(5S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiazepine S,S- dioxide		Z(c)

EXAMPLE 508

(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4-(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiazepine S,S-dioxide

[0899]
The title compound can be prepared by the procedures of Examples 504 and 482, by substituting an appropriate quantity of 2,6-difluoro-4-nitrobenzene (trifluoromethane) sulfonate for 3,4-difluoronitrobenzene in Step 1 of Example 482. [0900]

Utilizing the amine prepared in Example 508, but substituting the dithioester listed below for ethyl dithioacetate in the final step, the compounds of Examples 509 to 511 of Table O are obtained.

TABLE O


Example			Dithioester
No.	Compound	Amine	(from Preparation Z)


509	(5S)-N-[[3-[3,5- Difluoro-4-(4- thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiazepine S,S-dioxide		Z(a)

510	(5S)-N-[[3-[3,5- Difluoro-4-(4- thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiazepine S,S- dioxide		Z(b)

511	(5S)-N-[[3-[3,5- Difluoro-4-(4- thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiazepine S,S- dioxide		Z(c)

EXAMPLE 512

(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiazepine S,S-dioxide

[0902]
The title compound can be prepared by the procedure of Examples 504 and 482, by substituting an appropriate quantity of 4-fluoronitrobenzene for 3,4-difluoronitrobenzene in Step 1 of Example 482. [0903]

Utilizing the amine prepared in Example 512, but substituting the dithioester listed below for ethyl dithioacetate in the final step, the compounds of Examples 513 to 515 of Table P are obtained.

TABLE P


Example			Dithioester
No.	Compound	Amine	(From Preparation Z)


513	(5S)-N-[[3-[4- (tetrahydro-1,4- thiazepin-4(5H)- yl))phenyl]-2-oxo-5- oxazolidinyl]- methyl]propanethio- amide, thiazepine S,S- dioxide		Z(a)

514	(5S)-N-[[3-[4- (tetrahydro-1,4- thiazepin-4(5H)- yl))phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiazepine S,S- dioxide		Z(b)

515	(5S)-N-[[3-[4- (tetrahydro-1,4- thiazepin-4(5H)- yl))phenyl]-2-oxo-5- oxazolidinyl]- methyl]cyclopropane- carbothioamide, thiazepine S,S-dioxide		Z(c)

EXAMPLE 516

(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4-(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide

[0905]
This compound is prepared according to the procedure of Step 8 in Example 482, but stubstituting an appropriate quantity of ethyl dithioacetate for di-tert-butyl dicarbonate; mp 129-131° C. [0906]

Utilizing the amine prepared in Step 8 of Example 482, but substituting an appropriate quantity of the dithioester listed below for di-tert-butyl dicarbonate, the compounds of Examples 517 to 529 of Table Q are obtained.

TABLE Q


Example			Dithioester
No.	Compound	Amine	(From Preparation Z)


517	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide		Z(a)

518	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide		Z(b)

519	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide		Z(c)

520	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- butanethioamide		Z(d)

521	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide		Z(e)

522	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylbutanethioamide		Z(f)

523	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide		Z(g)

524	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothioamide		Z(h)

525	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopentanecarbothio- amide		Z(i)

526	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cylcohexanecarbothio- amide		Z(j)

527	(5S)-N-[[3-[3-5 Fluoro- 4-(tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethio- amide		Z(k)

528	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethio- amide		Z(l)

529	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylethanethioamide		Z(m)

EXAMPLE 530

(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide

[0908]
This compound can be prepared according to the procedures of Example 482 and Example 516, but substituting an appropriate quantity of 2,6-difluoro-4-nitrophenyl trifluoromethane sulfonate for 3,4-difluoronitrobenzene in Step 1 of Example 482. [0909]

Utilizing the amine prepared in Example 530, but substituting an appropriate quantity of the dithioester listed below for di-tert-butyl dicarbonate, the compounds of Examples 531 to 533 of Table R can be prepared.

TABLE R


Example			Dithio Compound
No.	Compound	Amine	(from Preparation Z)


531	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide		Z(a)

532	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide		Z(b)

533	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- yclopropanecarbothio- amide		(c)

EXAMPLE 534

(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide; mp 129-131° C.

[0911]
This compound can be prepared according to the procedures of Example 482 and Example 516, but substituting an appropriate quantity of 4-fluoronitrobenzene for 3,4-difluoronitrobenzene in Step 1 of Example 482. [0912]

Utilizing the amine prepared in Example 534, but substituting an appropriate quantity of the dithioester listed below for di-tert-butyl dicarbonate, the compounds of Examples 535 to 537 of Table S can be prepared.

TABLE S


Example			Dithio Compound
No.	Compound	Amine	(from Preparation Z)


535	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]- methyl]propanethio- amide		Z(a)

536	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide		Z(b)

537	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]- methyl]cyclopropane- carbothioamide		Z(c)

EXAMPLE 538

(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea, thiazepine S-oxide

[0914]
This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 482 for the amine [0915] 33.

By reaction of the isothiocyanate prepared in Example 538 with the amines and alcohols listed in Table T, the compounds of Examples 539 to 544 can be prepared.

TABLE T


Example			Amine or
No.	Compound	Isothiocyanate	Alcohol


539	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepine S-oxide		CH₃NH₂

540	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S-oxide		(CH₃)₂NH

541	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S-oxide		Azetidine

542	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate, thiazepine S-oxide		CH₃OH

543	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S-oxide		CH₃CH₂OH

544	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate, thiazepine S-oxide		(CH₃)₂CHOH

EXAMPLE 545

(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea, thiazepine S-oxide

[0917]
This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 496 for the amine [0918] 33.

By reaction of the isothiocyanate prepared in Example 545 with the amines and alcohols listed in Table U, the compounds of Examples 546 to 551 can be prepared.

TABLE U


Example			Amine or
No.	Compound	Isothiocyanate	Alcohol


546	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepine S-oxide		CH₃NH₂

547	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S-oxide		(CH₃)₂NH

548	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S-oxide		Azetidine

549	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate, thiazepine S-oxide		CH₃OH

550	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S-oxide		CH₃CH₂OH

551	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate, thiazepine S-oxide		(CH₃)₂CHOH

EXAMPLE 552

(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea, thiazepine S-oxide

[0920]
This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 500 for the amine [0921] 33.

By reaction of the isothiocyanate prepared in Example 552 with the amines and alcohols listed in Table V, the compounds of Examples 553 to 558 can be prepared.

TABLE V


Example			Amine or
No.	Compound	Isothiocyanate	Alcohol


553	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepine S-oxide		CH₃NH₂

554	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S-oxide		(CH₃)₂NH

555	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S-oxide		Azetidine

556	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate, thiazepine S-oxide		CH₃OH

557	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S-oxide		CH₃CH₂OH

558	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate, thiazepine S-oxide		(CH₃)₂CHOH

EXAMPLE 559

(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea, thiazepine S,S-dioxide

[0923]
This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 504 for the amine [0924] 33.

By reaction of the isothiocyanate prepared in Example 559 with the amines and alcohols listed in Table W, the compounds of Examples 560 to 565 can be prepared.

TABLE W


Example			Amine or
No.	Compound	Isothiocyanate	Alcohol


560	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepine S,S-dioxide		CH₃NH₂

561	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S,S-dioxide		(CH₃)₂NH

562	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S,S-dioxide		Azetidine

563	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate, thiazepine S,S-dioxide		CH₃OH

564	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S,S-dioxide		CH₃CH₂OH

565	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate, thiazepine S,S-dioxide		(CH₃)₂CHOH

EXAMPLE 566

(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea, thiazepine S,S-dioxide

[0926]
This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 508 for the amine [0927] 33.

By reaction of the isothiocyanate prepared in Example 566 with the amines and alcohols listed in Table X, the compounds of Examples 561 to 572 can be prepared.

TABLE X


Example			Amine or
No.	Compound	Isothiocyanate	Alcohol


567	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepine S,S-dioxide		CH₃NH₂

568	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S,S-dioxide		(CH₃)₂NH

569	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S,S-dioxide		Azetidine

570	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate, thiazepine S,S-dioxide		CH₃OH

571	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S,S-dioxide		CH₃CH₂OH

572	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate, thiazepine S,S-dioxide		(CH₃)₂CHOH

EXAMPLE 573

(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea, thiazepine S,S-dioxide

[0929]
This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 512 for the amine [0930] 33.

By reaction of the isothiocyanate prepared in Example 573 with the amines and alcohols listed in Table Y, the compounds of Examples 574 to 579 can be prepared.

TABLE Y


Example			Amine or
No.	Compound	Isothiocyanate	Alcohol


574	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepine S,S-dioxide		CH₃NH₂

575	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S,S-dioxide		(CH₃)₂NH

576	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S,S-dioxide		Azetidine

577	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate, thiazepine S,S-dioxide		CH₃OH

578	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S,S-dioxide		CH₃CH₂OH

579	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate, thiazepine S,S-dioxide		(CH₃)₂CHOH

EXAMPLE 580

(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

[0932]
This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Step 8 of Example 482 for the amine [0933] 33.

By reaction of the isothiocyanate prepared in Example 580 with the amines and alcohols listed in Table Z, the compounds of Examples 581 to 586 can be prepared.

TABLE Z


Example			Amine or
No.	Compound	Isothiocyanate	Alcohol


581	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea		CH₃NH₂

582	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea		(CH₃)₂NH

583	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide		Azetidine

584	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate		CH₃OH

585	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate		CH₃CH₂OH

586	(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate		(CH₃)₂CHOH

EXAMPLE 587

(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

[0935]
This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 530 for the amine [0936] 33.

By reaction of the isothiocyanate prepared in Example 587 with the amines and alcohols listed in Table AA, the compounds of Examples 588 to 593 can be prepared.

TABLE AA


Example			Amine or
No.	Compound	Isothiocyanate	Alcohol


588	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea		CH₃NH₂

589	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea		(CH₃)₂NH

590	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide		Azetidine

591	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate		CH₃OH

592	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate		CH₃CH₂OH

593	(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate		(CH₃)₂CHOH

EXAMPLE 594

(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

[0938]
This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 534 for the amine [0939] 33.

By reaction of the isothiocyanate prepared in Example 594 with the amines and alcohols listed in Table BB, the compounds of Examples 595 to 600 can be prepared.

TABLE BB


Example			Amine or
No.	Compound	Isothiocyanate	Alcohol


595	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea		CH₃NH₂

596	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea		(CH₃)₂NH

597	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide		Azetidine

598	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate		CH₃OH

599	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate		CH₃CH₂OH

600	(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate		(CH₃)₂CHOH

Claims

What is claimed:

1. A compound of the formula I

or pharmaceutical acceptable salts thereof wherein:

G is

R₁is

a) H,

b) NH₂,

c) NH—C_1-4alkyl,

d) C_1-4alkyl,

e) —OC_1-4alkyl,

f) —S C_1-4alkyl,

g) C_1-4alkyl substituted with 1-3 F, 1-2 Cl, CN or —COOC_1-4alkyl,

h) C_3-6cycloalkyl,

i) N(C_1-4) alkyl)₂or

j) N(CH₂)_2-5;

A is

wherein the 5-membered heteroaromatic moiety is bonded via a carbon atom,

wherein the heteroaromatic moiety is optionally substituted with one to three R₄₈,

e) a 6-membered heteroaromatic moiety having at least one nitrogen atom,

wherein the heteroaromatic moiety is bonded via a carbon atom,

wherein the heteroaromatic moiety is optionally substituted with one to three R₅₅,

f) a β-carbolin-3-yl, or indolizinyl bonded via the 6-membered ring, optionally substituted with one to three R₆₅,

wherein R₂is

a) H,

b) F,

c) Cl,

d) Br,

e) C_1-3alkyl,

f) NO₂, or

g) R₂and R₃taken together are —O—(CH₂)_h—O—;

R is

a) —S(═O)_iR₄,

b) —S(═O)₂—N═S(O)_jR₅R₆,

c) —SC(═O)R₇,

d) —C(═O)R₈,

e) —C(═O)R₉,

f) —C(═O)NR₁₀R₁₁,

g) —C(═NR₁₂)R₈,

h) —C(R₈)(R₁₁)—OR₁₃,

i) —C(R₉)(R₁₁)—OR₁₃,

j) —C(R₈)(R₁₁)—OC(═O)R₁₃,

k) —C(R₉)(R₁₁)—OC(═O)R₁₃,

l) —NR₁₀R₁₁,

m) —N(R₁₀)—C(═O)R₇,

n) —N(R₁₀)—S(═O)_iR₇,

o) —C(OR₁₄)(OR₁₅)R₈,

p) —C(R₈)(R₁₆)—NR₁₀R₁₁, or

q) C_1-8alkyl substituted with one or more ═O other than at alpha position, —S(═O)_iR₁₇, —NR₁₀R₁₁, C_2-5alkenyl, or C_2-5alkynyl;

R₄is

a) C_1-4alkyl optionally substituted with one or more halos, OH, CN, NR₁₀R₁₁, or —CO₂R₁₃,

b) C_2-4alkenyl,

c) —NR₁₆R₁₈,

d) —N₃,

e) —NHC(═O)R₇,

f) —NR₂₀C(═O)R₇,

g) —N(R₁₉)₂,

h) —NR₁₆R₁₉, or

i) —NR₁₉R₂₀,

R₅and R₆at each occurrence are the same or different and are

a) C_1-2alkyl, or

b) R₅and R₆taken together are —(CH₂)_k—;

R₇is C_1-4alkyl optionally substituted with one or more halos;

R₈is

a) H, or

b) C_1-8alkyl optionally substituted with one or more halos, or C_3-8cycloalkyl;

R₉is C_1-4alkyl substituted with one or more

a) —S(═O)R₁₇,

b) —OR₁₃,

c) —OC(═O)R₁₃,

e) C_1-5alkenyl optionally substituted with CHO;

R₁₀and R₁₁at each occurrence are the same or different and are

a) H,

b) C_1-4alkyl, or

c) C_3-8cycloalkyl;

R₁₂is

a) —NR₁₀R₁₁,

b) —OR₁₀; or

c) —NHC(═O)R₁₀;

R₁₃is

a) H, or

b) C_1-4alkyl;

R₁₄and R₁₅at each occurrence are the same or different and are

a) C_1-4alkyl, or

b) R₁₄and R₁₅taken together are —(CH)_l—;

R₁₆is

a) H,

b) C_1-4alkyl, or

c) C_3-8cycloalkyl;

R₁₇is

a) C_1-4alkyl, or

b) C_3-8cycloalkyl;

R₁₈is

a) H,

b) C_1-4alkyl,

c) C_2-4alkenyl,

d) C_3-4cycloalkyl,

e) —OR₁₃or

f) —NR₂₁R₂₂;

R₁₉is

a) Cl,

b) Br, or

c) I;

R₂₀is a physiologically acceptable cation;

R₂₁and R₂₂at each occurrence are the same or different and are

a) H,

b) C_1-4alkyl, or

c) —NR₂₁R₂₂taken together are —(CH₂₎ _m—;

wherein R₂₃and R₂₄at each occurrence are the same or different and are

a) H,

b) F,

c) Cl,

d) C_1-2alkyl,

e) CN

f) OH,

g) C_1-4alkoxy,

h) nitro, or

i) amino;

Q is

m) a diazinyl group optionally substituted with X and Y,

n) a triazinyl group optionally substituted with X and Y,

o) a quinolinyl group optionally substituted with X and Y,

p) a quinoxalinyl group optionally substituted with X and Y,

q) a naphthyridinyl group optionally substituted with X and Y,

Q and R₂₄taken together are

wherein Z¹is

a) —CH₂—,

b) —CH(R¹⁰⁴)—CH₂—,

c) —C(O)—, or

d) —CH₂CH₂CH₂—;

wherein Z²is

a) —O₂S—,

b) —O—,

c) —N(R¹⁰⁷)—,

d) —OS—, or

e) —S—;

wherein Z³is

a) —O₂S—,

b) —O—,

c) —OS—, or

d) —S—;

wherein A¹is

a) H—, or

b) CH₃;

wherein A²is

a) H—,

b) HO—,

c) CH₃—,

d) CH₃O—,

e) R¹⁰²O—CH₂—C(O)—NH—

f) R¹⁰³O—C(O)—NH—,

g) (C₁-C₂)alkyl—O—C(O)—,

h) HO—CH₂—,

i) CH₃O—NH—,

j) (C₁-C₃)alkyl—O₂C—

k) CH₃—C(O)—,

l) CH₃—C(O)—CH₂,

A¹and A²taken together are:

wherein R¹⁰²is

a) H—,

b) CH₃—,

c) phenyl-CH₂— or

d) CH₃C(O)—;

wherein R¹⁰³is

a) (C₁-C₃)alkyl-, or

b) phenyl-;

wherein R¹⁰⁴is

a) H—, or

b) HO—;

wherein R¹⁰⁵is

a) H—,

b) (C₁-C₃)alkyl-,

c) CH₂═CH—CH₂—, or

d) CH₃—O—(CH₂)₂—;

wherein R¹⁰⁶is

a) CH₃—C(O)—,

b) H—C(O)—,

c) Cl₂CH—C(O)—,

d) HOCH₂—C(O)—,

e) CH₃SO₂—,

g) F₂CHC(O)—,

i) H₃C—C(O)—O—CH₂—C(O)—,

j) H—C(O)—O—CH₂—C(O)—,

l) HC≡C—CH₂O—CH₂—C(O)—, or

m) phenyl-CH₂—CH₂—O—CH₂—C(O)—;

wherein R¹⁰⁷is

a) R¹⁰²O—C(R¹¹⁰)(R¹¹¹)—C(O)—,

b) R¹⁰³O—C(O)—,

c) R¹⁰⁸—C(O)—,

f) H₃C—C(O)—(CH₂)₂—C(O)—,

g) R¹⁰⁹—SO₂—,

i) HO—CH₂—C(O)—,

j) R¹¹⁶—(CH₂)₂—,

k) R¹¹³—C(O)—O—CH₂—C(O)—,

l) (CH₃)₂N—CH₂—C(O)—NH—,

m) NC—CH₂—,

n) F₂—CH—CH₂—, or

o) R¹⁵⁰R¹⁵¹NSO₂—;

wherein R¹⁰⁸is

a) H—,

b) (C₁-C₄)alkyl,

c) aryl —(CH₂)_p,

d) ClH₂C—,

e) Cl₂HC—,

f) FH₂C—,

g) F₂HC—,

h) (C₃-C₆)cycloalkyl, or

i) CNCH₂—;

wherein R¹⁰⁹is

a) (C₁-C₄)alkyl,

b) —CH₂Cl

c) —CH₂CH═CH₂,

d) aryl, or

e) —CH₂CN;

wherein R¹¹⁰and R¹¹¹are independently

a) H—,

b) CH₃—; or

wherein R¹¹²is

a) H—,

b) CH₃O—CH₂O—CH₂—, or

c) HOCH₂—;

wherein R¹¹³is

a) CH₃—,

b) HOCH₂—,

c) (CH₃)₂N-phenyl, or

d) (CH₃)₂N—CH₂—;

wherein R¹¹⁴is

a) HO—,

b) CH₃O—,

c) H₂N—,

d) CH₃O—C(O)—O—,

e) CH₃—C(O)—O—CH₂—C(O)—O—,

f) phenyl-CH₂—O—CH₂—C(O)—O—,

g) HO—(CH₂)₂—O—,

h) CH₃O—CH₂—O—(CH₂)₂—O—, or

i) CH₃O—CH₂—O—;

wherein R¹¹³is

a) CH₃—,

b) HOCH₂—,

c) (CH₃)₂N-phenyl, or

d) (CH₃)₂N—CH₂—;

wherein R¹¹⁵is

a) H—, or

b) Cl—;

wherein R¹¹⁶is

a) HO—

b) CH₃O—, or

c) F;

wherein R¹⁵⁰and R¹⁵¹are each H or alkylC₁-C₄or R¹⁵⁰and R¹⁵¹taken together with the nitrogen atom to which each is attached form a monocyclic heterocyclic ring having from 3 to 6 carbon atoms;

B is an unsaturated 4-atom linker having one nitrogen and three carbons;

M is

a) H,

b) C_1-8alkyl,

c) C_3-8cycloalkyl,

d) —(CH₂)_mOR₁₃, or

e) —(CH₂)_h—NR₂₁R₂₂;

Z is

a) O,

b) S, or

c) NM;

W is

a) CH,

b) N, or

c) S or O when Z is NM;

Y is

a) H,

b) F,

c) Cl,

d) Br,

e) C_1-3alkyl, or

f) NO₂;

X is

a) H,

b) —CN,

c) OR₂₇,

d) halo,

e) NO₂,

f) tetrazoyl,

g) —SH,

h) —S(═O)_i—R₄,

i) —S(═O)₂—N═S(O)_jR₅R₆,

j) —SC(═O)R₇,

k) —C(═O)R₂₅,

l) —C(═O)NR₂₇R₂₈,

m) —C(═NR₂₉)R₂₅,

n) —C(R₂₅)(R₂₈)—OR₁₃,

o) —C(R₂₅)(R₂₈)—OC(═O)R₁₃,

p) —C(R₂₈)(OR₁₃)—(CH₂)_h—NR₂₇R₂₈,

q) —NR₂₇R₂₈,

r) —N(R₂₇)C(═O)R₇,

s) —N(R₂₇)—S(═O)_iR₇,

t) —C(OR₁₄)(OR₁₅)R₂₈,

u) —C(R₂₅)(R₁₆)—NR₂₇R₂₆, or

v) C_1-8alkyl substituted with one or more halos, OH, ═O other than at alpha position, —S(═O)_i—R₁₇, —NR₂₇R₂₈, C_2-5alkenyl, C_2-5alkynyl, or C_3-8cycloalkyl;

R₄, R₅, R₆, R₇, R₁₃, R₁₄, R₁₅, R₁₆, and R₁₇are the same as defined above;

R₂₅is

a) H,

b) C_1-4alkyl optionally substituted with one or more halos, C_3-8cycloalkyl, C_1-4alkyl substituted with one or more of —S(═O)_iR₁₇, —OR₁₃, or OC(═O)R₁₃, NR₂₇R₂₈, or

c) C_2-5alkenyl optionally substituted with CHO, or CO₂R₁₃;

R₂₆is

a) R₂₈, or

b) NR₂₇N₂₈;

R₂₇and R₂₈at each occurrence are the same or different and are

a) H,

b) C_1-8alkyl,

c) C_3-8cycloalkyl,

d) —(CH₂)_mOR₁₃,

e) —(CH₂)_h—NR₂₁R₂₂, or

f) R₂₇and R₂₈taken together are —(CH₂)₂O(CH₂)₂—, —(CH₂)_hCH(COR₇)—, or —(CH₂)₂N(CH₂)₂(R₇);

R₂₉is

a) —NR₂₇R₂₈,

b) —OR₂₇, or

c) —NHC(═O)R₂₈;

wherein R₃₀is

a) H,

b) C_1-8alkyl optionally substituted with one or more halos, or

c) C_1-8alkyl optionally substituted with one or more OH, or C_1-6alkoxy,

wherein E is

a) NR₃₉,

b) —S(═O)_i, or

c) O;

R₃₈is

a) H,

b) C_1-6alkyl,

c) —(CH₂)_q-aryl, or

d) halo;

R₃₉is

a) H,

b) C_1-6alkyl optionally substituted with one or more OH, halo, or —CN,

c) —(CH₂)_q-aryl,

d) —CO₂R₄₀,

e) —COR₄₁,

f) —C(═O)—(CH₂)_q—C(═O)R₄₀,

g) —S(═O)₂—C_1-6alkyl,

h) —S(═O)₂—(CH₂)_q-aryl, or

i) —(C═O)_j-Het;

R₄₀is

a) H,

b) C_1-6alkyl optionally substituted with one or more OH, halo, or —CN,

c) —(CH₂)_q-aryl, or

d) —(CH₂)_q—OR₄₂;

R₄₁is

a) C_1-6alkyl optionally substituted with one or more OH, halo, or —CN,

b) −(CH₂)_q-aryl, or

c) —(CH₂)_q—OR₄₂;

R₄₂is

a) H,

b) C_1-6alkyl,

c) —(CH₂)_q-aryl, or

d) —C(═O)—C_1-6alkyl;

aryl is

a) phenyl,

b) pyridyl, or

c) napthyl; a to c optionally substituted with one or more halo, —CN, OH, SH, C_1-6alkyl, C_1-6alkoxy, or C_1-6alkylthio;

wherein R₄₃is

a) H,

b) C_1-2alkyl,

c) F, or

d) OH;

R₄₄is

a) H,

b) CF₃,

c) C_1-3alkyl optionally substituted with one or more halo,

d) phenyl optionally substituted with one or more halo,

e) R₄₄and R₄₅taken together are a 5-, 6-, or 7-membered ring of the formula,

or

f) R₄₄and R₄₅taken together are —(CH₂)_k—, when R₄₆is an electron-withdrawing group;

R₄₅and R₄₆at each occurrence are the same or different and are

a) an electron-withdrawing group,

b) H,

c) CF₃,

d) C_1-3alkyl optionally substituted with one halo,

e) phenyl provided at least one of R₄₅or R₄₆is an electron-withdrawing group, or

f) R₄₅and R₄₆taken together are a 5-, 6-, 7-membered ring of the formula

U is

a) CH₂,

b) O,

c) S, or

d) NR₄₇;

R₄₇is

a) H, or

b) C_1-5alkyl;

wherein R₄₈is

a) carboxyl,

b) halo,

c) —CN,

d) mercapto,

e) formyl,

f) CF₃,

g) —NO₂,

h) C_1-6alkoxy,

i) C_1-6alkoxycarbonyl,

j) C_1-6alkythio,

k) C_1-6acyl,

l) —NR₄₉R₅₀,

m) C_1-6alkyl optionally substituted with OH, C_1-5alkoxy, C_1-5acyl, or —NR₄₉R₅₀,

n) C_2-8alkenylphenyl optionally substituted with one or two R₅₁,

o) phenyl optionally substituted with one or two R₅₁,

p) a 5-, or 6-membered (un)saturated heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, optionally substituted with one or two R₅₁, or

R₄₉and R₅₀at each occurrence are the same or different and are

a) H,

b) C_1-4alkyl,

c) C_5-6cycloalkyl, or

d) R₄₉and R₅₀taken together with the nitrogen atom is a 5-, 6-membered saturated heterocyclic moiety which optionally has a farther hetero atom selected from the group consisting of S, N, and O, and can in turn be optionally substituted with, including on the further nitrogen atom, C_1-3alkyl, or C_1-3acyl;

R₅₁is

a) carboxyl,

b) halo,

c) —CN,

d) mercapto,

e) formyl,

f) CF₃,

g) —NO₂,

h) C_1-6alkoxy,

i) C_1-6alkoxycarbonyl,

j) C_1-6alkythio,

k) C_1-6acyl,

l) C_1-6alkyl optionally substituted with OH, C_1-5alkoxy, C_1-5acyl, or —NR₄₉R₅₀,

m) phenyl,

n) —C(═O)NR₅₂R₅₃,

o) —NR₄₉R₅₀,

p) —N(R₅₂)(—SO₂R₅₄),

q) —SO₂—NR₅₂R₅₃, or

r) —S(═O)_iR₅₄;

R₅₂and R₅₃at each occurrence are the same or different and are

a) H,

b) C_1-6alkyl, or

c) phenyl;

R₅₄is

a) C_1-4alkyl, or

b) phenyl optionally substituted with C_1-4alkyl;

wherein R₅₅is

a) carboxyl,

b) halo,

c) —CN,

d) mercapto,

e) formyl,

f) CF₃,

g) —NO₂,

h) C_1-6alkoxy,

i) C_1-6alkoxycarbonyl,

j) C_1-6alkythio

k) C_1-6acyl,

l) —NR₅₆R₅₇,

m) C_1-4alkyl optionally substituted with OH, C_1-5alkoxy, C_1-5acyl, or —NR₅₆R₅₇,

n) C_2-8alkenylphenyl optionally substituted with one or two R₅₈,

o) phenyl optionally substituted with one or two R₅₈,

p) a 5- or 6-membered (un)saturated heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, optionally substituted with one or two R₅₈, or

R₅₆and R₅₇at each occurrence are the same or different and are

a) H,

b) formyl,

c) C_1-4alkyl

d) C_1-4acyl,

e) phenyl,

f) C_3-6cycloalkyl, or

g) R₅₆and R₅₇taken together with the nitrogen atom is a 5-, 6-membered saturated heterocyclic moiety which optionally has a further hetero atom selected from the group consisting of S, N, and O, and can in turn be optionally substituted with, including on the further nitrogen atom, phenyl, pyrimidyl, C_1-3alkyl or C_1-3acyl;

R₅₈is

a) carboxyl,

b) halo,

c) —CN,

d) mercapto,

e) formyl,

f) CF₃,

g) —NO₂,

h) C_1-6alkoxy,

i) C_1-6alkoxycarbonyl,

j) C_1-6alkythio,

k) C_1-6acyl,

l) phenyl,

m) C_1-6alkyl optionally substituted with OH, azido, C_1-5alkoxy, C_1-5acyl, —NR₆₅R₅₆, —SR₅₇, —O—SO₂R₆₈, or

n) —C(═O)NR₅₉R₆₀,

o) —NR₅₆R₅₇,

p) —N(R₅₉)(SO₂R₅₄),

q) —SO₂—NR₅₉R₆₀,

r) —S(═O)_i—R₅₄,

s) —CH═N—R₆₁, or

t) —CH(OH)—SO₃R₆₄;

R₅₄is the same as defined above;

R₅₉and R₆₀at each occurrence are the same or different and are

a) H,

b) C_1-6alkyl,

c) phenyl, or

d) tolyl;

R₆₁is

a) OH,

b) benzyloxy,

c) —NH—C(═O)—NH₂,

d) —NH—C(═S)—NH₂, or

e) —NH—C(═NH)—NR₆₂R₆₃;

R₆₂and R₆₃at each occurrence are the same or different and are

a) H, or

b) C_1-4alkyl optionally substituted with phenyl or pyridyl;

R₆₄is

a) H, or

b) a sodium ion;

R₆₅and R₆₆at each occurrence are the same or different and are

a) H,

b) formyl,

c) C_1-4alkyl,

d) C_1-4acyl,

e) phenyl,

f) C_3-6cycloalkyl,

g) R₆₅and R₆₆taken together are a 5-, 6-membered saturated heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, optionally substituted with, including on the nitrogen atom, phenyl, pyrimidyl, C_1-3alkyl, or C_1-3acyl,

h) —P(O)(OR₇₀)(OR₇₁), or

i) —SO₂—R₇₂;

R₆₇is

R₆₈is C_1-3alkyl;

R₆₉is

a) C_1-6alkoxycarbonyl, or

b) carboxyl;

R₇₀and R₇₁at each occurrence are the same or different and are

a) H, or

b) C_1-3alkyl;

R₇₂is

a) methyl,

b) phenyl, or

c) tolyl;

wherein K is

a) O, or

b) S;

R₇₃, R₇₄, R₇₅, R₇₆, and R₇₇at each occurrence are the same or different and are

a) H,

b) carboxyl,

c) halo,

d) —CN,

e) mercapto,

f) formyl,

g) CF₃,

h) —NO₂,

i) C_1-6alkoxy,

j) C_1-6alkoxycarbonyl,

k) C_1-6alkythio,

l) C_1-6acyl,

m) —NR₇₈R₇₉,

n) C_1-6alkyl optionally substituted with OH, C_1-5alkoxy, C_1-5acyl, —NR₇₈R₇₉, —N(phenyl)(CH₂—CH₂—OH), —O—CH(CH₃)(OCH₂CH₃), or —O-phenyl-[para-NHC(═O)CH₃],

o) C_2-8alkenylphenyl optionally substituted with R₅₁,

p) phenyl optionally substituted with R₅₁, or

q) a 5-, or 6-membered (un)saturated heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, optionally substituted with R₅₁;

R₅₁is the same as defined above;

R₇₈and R₇₉at each occurrence are the same or different and are

a) H,

b) C_1-4alkyl,

c) phenyl, or

d) R₇₈and R₇₉taken together with the nitrogen atom is a 5-, 6-membered saturated heterocyclic moiety which optionally has a further hetero atom selected from the group consisting of S, N, and O, and can in turn be optionally substituted with, including on the nitrogen atom, C_1-3alkyl, or C_1-3acyl;

further wherein T is

a) O,

b) S, or

c) SO₂;

R₇₅, R₇₆, and R₇₇are the same as defined above;

R₈₀is

a) H,

b) formyl,

c) carboxyl,

d) C_1-6alkoxycarbonyl,

e) C_1-8alkyl,

f) C_2-8alkenyl,

wherein the substituents (e) and (f) can be optionally substituted with OH, halo, C_1-6alkoxy, C_1-6acyl, C_1-6alkylthio or C_1-6alkoxycarbonyl, or phenyl optionally substituted with halo,

g) an aromatic moiety having 6 to 10 carbon atoms optionally substituted with carboxyl, halo, —CN, formyl, CF₃, —NO₂, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl, C_1-6alkylthio, or C_1-6alkoxycarbonyl;

h) —NR₈₁R₈₂,

i) —OR₉₀,

j) —S(═O)_i—R₉₁,

k) —SO₂—N(R₉₂)(R₉₃), or

l) a radical of the following formulas:

R₈₁and R₈₂at each occurrence are the same or different and are

a) H,

b) C_3-6cycloalkyl,

c) phenyl,

d) C_1-6acyl,

e) C_1-8alkyl optionally substituted with OH, C_1-6alkoxy which can be substituted with OH, a 5-, or 6-membered aromatic heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, phenyl optionally substituted with OH, CF₃, halo, —NO₂, C_1-4alkoxy, —NR₈₃R₈₄, or

V is

a) O,

b) CH₂, or

c) NR₈₇;

R₈₃and R₈₄at each occurrence are the same or different and are

a) H, or

b) C_1-4alkyl;

R₈₅is

a) OH,

b) C_1-4alkoxy, or

c) —NR₈₈R₈₉;

R₈₆is

a) H, or

b) C_1-7alkyl optionally substituted with indolyl, OH, mercaptyl, imidazoly, methylthio, amino, phenyl optionally substituted with OH, —C(═O)—NH₂, —CO₂H, or —C(═NH)—NH₂;

R₈₇is

a) H,

b) phenyl, or

c) C_1-6alkyl optionally substituted by OH;

R₈₈and R₈₉at each occurrence are the same or different and are

a) H,

b) C_1-6alkyl

c) C_1-6cycloalky, or

d) phenyl;

R₉₀is

a) C_1-8alkyl optionally substituted with C_1-6alkoxy or C_1-6hydroxy, C_3-6cycloalkyl, a 6-membered aromatic optionally benzo-fused heterocyclic moiety having one to three nitrogen atoms, which can in turn be substituted with one or two —NO₂, CF₃, halo, —CN, OH, C_1-5alkyl, C_1-5alkoxy, or C_1-5acyl;

c) phenyl, or

d) pyridyl;

R₉₁is

a) C_1-16alkyl,

b) C_2-16alkenyl,

wherein the substituents (a) and (b) can be optionally substituted with C_1-6alkoxycarbonyl, or a 5-, 6-, 7-membered aromatic heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O,

c) an aromatic moiety having 6 to 10 carbon atoms, or

d) a 5-, 6-, 7-membered aromatic heterocyclic moiety having one to three atoms selected from the group consisting of S. N, and O,

wherein the substituents (c) and (d) can be optionally substituted with carboxyl, halo, —CN, formyl, CF₃, —NO₂, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl, C_1-6alkylthio, or C_1-6alkoxycarbonyl;

R₉₂and R₉₃at each occurrence are the same or different and are

a) H,

b) phenyl,

c) C_1-6alkyl, or

d) benzyl;

R₉₄and R₉₅at each occurrence are the same or different and are

a) H,

b) OH,

c) C_1-6alkyl optionally substituted with —NR₈₃R₈₄, or

d) R₉₄and R₉₅taken together are ═O;

R₉₆is

a) an aromatic moiety having 6 to 10 carbon atoms,

wherein the substituents (a) and (b) which can in turn be substituted with one or three —NO₂, CF₃, halo, —CN, OH, phenyl, C_1-5alkyl, C_1-5alkoxy, or C_1-5acyl,

c) morpholinyl,

d) OH,

e) C_1-6alkoxy,

f) —NR₈₃R₈₄,

g) —C(═O)—R₉₇, or

R₉₇is

a) morpholinyl,

b) OH, or

c) C_1-6alkoxy;

h is 1, 2, or 3;

i is 0, 1, or 2;

j is 0 or 1;

k is 3, 4, or 5;

l is 2 or 3;

m is 4 or 5;

n is 0, 1, 2, 3, 4, or 5;

q is 1, 2, 3, or 4;

r is 2, 3, or 4;

t is 0, 1, 2, 3, 4, 5, or 6;

u is 1 or 2;

w is 0, 1, 2, or 3.

2. A compound of claim 1 which is:

a) (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;

b) (S)-N-[[3-[3-Fluoro-4-[4-(5-methyl1,3,4-thiadiazol2-yl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;

c) (S)-N-[[3-[3-Fluoro-4-[2′,6′-dioxospiro[piperidine-4,4′-imidazolidine]1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;

d) (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;

e) (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea;

f) (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea;

g) (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-thioformamide;

h) (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiopropion-amide;

i) (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-chlorothioacetamide;

j) (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α,α-trifluorothioacetamide;

k) (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-fluorothioacetamide;

l) (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α-difluorothioacetamide;

m) (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-cyanothioacetamide;

n) (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α-dichlorothioacetamide;

o) (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-(methoxycarbonyl)thioacetamide;

p) (S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;

q) (S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;

r)) (S)-N-[[3-[1-(Hydroxyacetyl)-5-indolinyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;

s) (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;

t) (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio-acetamide;

u) (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiomorpholine S-oxide;

v) (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio-acetamide, thiomorpholine S, S-dioxide;

w) (S)-N-[[3-[3,5-Difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;

x) (S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea;

y) (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea;

z) (S)-N-[[3-[1-(Hydroxyacetyl)-5-indolinyl]-2-oxo-5-oxazolidinyl]methyl]thiourea;

aa) (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methylthiourea, thiomorpholine S-oxide;

bb) (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-S-methyldithiocarbamate;

3. A compound of claim 1 which is (S)-trans-N-[[3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide.

4. A compound of claim 1 which is (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiomorpholine S-oxide.

5. A method for treating microbial infections in patients comprising administering to a patient in need thereof an effective amount of a compound of Formula I.

6. A compound of claim 1 wherein G is

7. A compound of claim 1 wherein A is

8. A compound of claim 7 wherein Q is

9. A compound of claim 1 wherein G is

10. A compound of claim 9 wherein Z²is —O₂S—.

11. A compound of claim 10 which is (5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiazepine S,S-dioxide.

12. A compound of claim 9 wherein Z²is —OS—.

13. A compound of claim 12 which is

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide, thiomorpholine S-oxide;

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide, thiomorpholine S-oxide;

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothio-amide, thiomorpholine S-oxide;

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate, thiomorpholine S-oxide;

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate, thiomorpholine S-oxide;

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate, thiomorpholine S-oxide;

(5S)-N-[[3-[3-Fluoro-4-tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiazepine S-oxide,

(5S)-N-[[3-[3-Fluoro-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea, thiomorpholine S-oxide, or

(5S)-N-[[3-[3-Fluoro-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide, thiomorpholine S-oxide.

14. A compound of claim 9 wherein Z²is O.

15. A compound of claim 14 which is

(S)-N-[[3-[3-Fluoro-4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate;

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide;

(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane-carbothioamide

16. A compound of claim 9 wherein Z²is —S—.

17. A compound of claim 9 which is (5S)-N-[[3-[4-(tetrahydro-1,4-thiazepine-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide.

18. A compound of claim 9 wherein Z²is —N(R¹⁰⁷)—.

19. A compound of claim 16 which is

(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl-2-oxo-5-oxazolidinyl]methyl]propanethiomide;

(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide;

(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide;

(S)-N-[[3-[3-Fluoro-4-acetyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;

(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide;

(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide;

(S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide;

(S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide;

(S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;

(S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide;

(S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide;

(S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide; or

(S)-N-[[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide.