MXPA99006526A

MXPA99006526A - New carbapenem derivatives

Info

Publication number: MXPA99006526A
Application number: MXPA/A/1999/006526A
Authority: MX
Inventors: Kano Yuko; Ida Takashi; Sasaki Toshiro; Fushihara Kenichi; Aihara Kazuhiro; Toyooka Yumiko; Takizawa Hiromasa; Kobayashi Kazuko; Atsumi Kunio; Iwamatsu Katsuyoshi
Original assignee: Meiji Seika Kaisha Ltd
Priority date: 1997-01-28
Filing date: 1999-07-13
Publication date: 2000-11-01

Abstract

New carbapenem derivatives of general formula (I) wherein R1 represents hydrogen or methyl;one of R2, R3, R4 and R5 represents a bond at the 2-position of the carbapenem ring and other three of them represent each hydrogen, halogen, nitro, cyano, alkyl, cycloalkyl, alkylthio, alkenyl, formyl, alkylcarbonyl, alkoxycarbonyl, aminosulfonyl, arylcarbonyl, aryl, carbamoyl, N-(lower alkyl)carbamoyl, N,N-di(lower alkyl)aminocarbonyl, lower alkoxyiminomethyl or hydroxyiminomethyl;R6 is not present or represents alkyl, cycloalkyl or alkenyl;R is absent or represents hydrogen or a group hydrolyzable in vivo, provided when R6 is absent, R represents hydrogen or a group hydrolyzable in vivo and when R6 is present, R is absent and an inner salt is formed. The compounds have patent antimicrobial activities against meticillin-resistant Staphylococcus aureus, penicillin-resistant pneumococcus, enterococcus, influenza virus and&bgr;-lactamase-producing microbes, and are highly resistant to DHP-1.

Description

"DERIVADOS DE CARBAPENEM NOVEDOSOS" BACKGROUND OF THE INVENTION FIELD OF THE INVENTION The present invention relates to a carbapenem compound having excellent antimicrobial activity, and a broad scale of anti-microbial spectrum, and which can be administered not only as an injection but also orally. More particularly, the present invention relates to a novel carbapenem derivative having a substituted or unsubstituted imidazo [5, 1-b] thiazole group or a substituted or unsubstituted imidazo [5, 1-b] thiazolium group in the position 2 in the ring of carbapenem, or a salt thereof.

ANTECEDENTS OF THE TECHNIQUE Carbapenem derivatives, due to the potent antibacterial activity against a broad spectrum of bacteria, have been energetically studied as a highly useful β-lactam agent and Imipenem, Panipenem and Meropenem have been used clinically. Both Imipenem and Panipenem, however, are used as a mixture due to their instability against the - - dehydropeptidase-1-renal ("DHP-1") in the case of Impene and in order to reduce nephrotoxicity in the case of Panipenem. Meropenem, which has recently been sold, has a methyl group in the Iß position, so that it has increased stability with respect to DHP-1 and can therefore be used alone. However, there is still a need for a drug that has greater stability to DHP-1. In addition, effective drugs for methicillin-resistant Staphylococcus aureus ("MRSA"), penicillin-resistant Streptococcus pneumoneae ("PRSP"), Pseudomonas aeruginosa and resistant enterococci have recently become serious problems as well as influenza, have been requested Likewise. Some of the present inventors have previously reported about the carbapenem derivatives having an imidazo [5, 1-b] thiazolium-6-ylmethyl group in the novel heteroaromatic ring at the 2-position in the carbapenem ring in Patent Number WO 96/028455 and the carbapenem derivatives having an imidazo [5, 1-b] thiazole group through a pyrrolidinylthio group at the 2-position of the carbapenem ring in Patent Number PCT / JP 97/04270. In addition, Patent Number WO 96/034868 and Japanese Patent Publication Number 273876/1992 give a - know the carbapenem derivatives wherein a carbon atom in the heteroaromatic ring is linked to the 2-position of the carbapenem ring. However, specific data on antimicrobial activities or efficacy for these derivatives have not been described. Neither bicyclic heteroaromatic rings nor carbapenem rings having the imidazole [5, 1-b] thiazole group have been described.

COMPENDIUM OF THE INVENTION The present inventors have now found that novel carbapenem derivatives having a substituted or unsubstituted imidazo [5, 1-b] thiazole group or an imidazo [5, 1-b] thiazolium group substituted or unsubstituted at position 2 in The ring of carbapenem have large anti-microbial activities against MRSA, PRSP, enterococci, influenza and ß-lactamase-producing bacteria, and large stabilities to DHP-1. The present invention is based on these findings. Therefore, the object of the present invention is to provide novel compounds having a broad scale of anti-microbial activities, especially large anti-microbial activities against microorganisms including MRSA, PRSP, enterococci, influenza and ß-lactamase-producing bacteria, and great stabilities to the DHP-1. Therefore, the present invention provides a compound represented by the formula (I), or a pharmacologically acceptable salt thereof: (I) wherein: R1 represents hydrogen or methyl, R2, R3, R4 and R5 / any of which represent the bond to position 2 in the carbapenem ring, and the remaining three groups which may be the same or different, represent respectively. hydrogen, halogen, nitro, cyano, lower alkyl, wherein one or more hydrogen atoms in the alkyl may be substituted by a group selected from the group consisting of halogen, nitro, - - cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl , aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and aryl, lower cycloalkyl , wherein one or more of the hydrogen atoms in the cycloalkyl can be substituted by a group selected from the group consisting of lower alkyl, halogen, nitro, cyano, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino , formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di-alkylaminocarbon lower ilo, aminosulfonyl, (n-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (lower N-alkylamino) sulfonylamino, aminosulfonylamino, (lower N, N-di-alkylamino (sulfonylamino, and aryl, lower alkylthio, alkenyl of 2 to 4 carbon atoms, wherein one or more of the hydrogen atoms in the alkenyl can be substituted - - by a group selected from the group consisting of lower alkyl, halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino , aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and aryl, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, lower alkylsulfonyl, arylsulfonyl, aminosulfonyl, arylcarbonyl, aryl, wherein one or more hydrogen atoms in the aryl can be substituted by a group selected from the group consisting of lower alkyl, halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy r, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, - - lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-alkylamino lower) sulfonylamino, aminosulfonylamino, and (N, N-di-lower alkylamino) sulfonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxy-inomethyl, R is not present, or represents alkyl lower, wherein one or more of the hydrogen atoms in the alkyl may be substituted by a group selected from the group consisting of halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N- lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di-alkylaminocarboni the lower, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and aryl, lower cycloalkyl, wherein one or more of the hydrogen atoms in the cycloalkyl can be substituted by a group selected from the group consisting of lower alkyl, halogen, nitro, cyano, lower alkylthio, lower alkoxy, hydroxy, amino, N -alkylamino lower, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl , (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and aryl, or alkenyl of 2 to 4 carbon atoms, wherein one or more of the hydrogen atoms in the alkenyl is it can be substituted by a group selected from the group consisting of lower alkyl, halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, alkoxycarbonyl lower, formylamino, lower alkylcarbonylamino, carbamoyl, lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino (sulfonyl, (N, N-di-alkylamino - - lower) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino and aryl, and R is not present, or represents hydrogen or a group that can be hydrolyzed metabolically in the body, provided that when R ^ is not present, R represents hydrogen or a group that can hydrolyze metabolically in the body, and when R6 is present, R is not present, and the compound forms an internal salt.

DETAILED DESCRIPTION OF THE INVENTION As used herein, the term "lower alkyl" or "lower alkoxy" as a group or a part of the group means a straight chain or branched chain alkyl or alkyloxy having from 1 to 6 carbon atoms, preference of 1 to 4 carbon atoms. Examples of the lower alkyl include methyl, ethyl, N-propyl, isopropyl, N-butyl, i-butyl, s-butyl, t-butyl, N-pentyl, N-hexyl and the like. In addition, lower alkoxy includes, by way of example, methoxy, ethoxy, N-propoxy, i-propoxy, N-butoxy, i-butoxy, s-butoxy, t-butoxy and the like.

- The term "lower cycloalkyl" means monocyclic alkyl having from 3 to 6 carbon atoms. The term "halogen" herein means fluorine, chlorine, bromine or iodine. In addition, the term "aryl" preferably means phenyl or naphthyl. Compound In formula (I), any of R2, R3, R4 and R5 represents the bond to position 2 in the carbapenem ring. The remaining three groups, which may be the same or different, respectively represent hydrogen, halogen, nitro, cyano, lower alkyl which may be substituted, lower cycloalkyl which may be substituted, lower alkylthio, alkenyl of 2 to 4 carbon atoms which may be substituted , formyl, lower alkylcarbonyl, lower alkoxycarbonyl, lower alkylsulfonyl, arylsulfonyl, aminosulfonyl, arylcarbonyl, aryl that can be substituted, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl. According to the preferred embodiment of the present invention, the three remaining groups preferably are hydrogen, halogen, cyano, lower alkyl, which can be substituted, formyl, lower alkylcarbonyl, - - lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-alkylcarba lower alkyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl or hydroxyiminomethyl, more preferably hydrogen, chloro, cyano, lower alkyl, substitutable, formyl, lower alkylcarbonyl, alkoxycarbonyl lower, carbamoyl, lower N-alkylcarbamoyl or N, N-di-lower alkylaminocarbonyl. Where R ^, R3, R4 and R5 represent lower alkyl, one or more of the hydrogen atoms in the lower alkyl can be substituted by halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-alkylcarba lower alkyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) sulfonyl, ( N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, -di-lower alkylamino) sulfonylamino, and aryl. In accordance with the preferred embodiment of the present invention, the substituent preferably includes lower alkoxy, hydroxy, formylamino, and carbamoyl, particularly lower alkoxy, hydroxy, and formylamino. He - - substituted alkyl includes for example aminomethyl, hydroxymethyl, 2-hydroxyethyl, carbamoylmethyl, 2-carbamoylethyl, 2-fluoroethyl, cyclopropylmethyl, 2- (N-methylcarbamoyl) ethyl, N, N-dimethylcarbamoylmethyl, 2- (N, N-dimethylcarbamoyl) ethyl , 2-aminosulfonylethyl, aminosulfonylamino ethyl, 2- (aminosulfonylamino) ethyl, methoxymethyl, ethoxycarbonylmethyl, for ilaminomethyl, methoxyiminomethyl, hydroxyiminoethyl, benzyl. In R2, R3, R and R5 which represents cycloalkyl, one or more of the hydrogen atoms in the cycloalkyl can be substituted by a group selected from the group consisting of lower alkyl, halogen, nitro, cyano, lower alkylthio, lower alkoxy , hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino ) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and aryl. According to the preferred embodiment of the present invention, the substituent includes, for example, lower alkoxy, hydroxy, formylamino and carbamoyl, particularly lower alkoxy, hydroxy and formylamino.

- - In addition, in R2, R3, R4 and R5 representing alkenyl, one or more of the hydrogen atoms in the alkenyl can be substituted and the substituent includes for example a group selected from the group consisting of lower alkyl, halogen, nitro , cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di - lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and aryl . In accordance with the preferred embodiment of the present invention, the preferred substituent includes, for example, lower alkoxy, hydroxy, formylamino, and carbamoyl, particularly lower alkoxy, hydroxy, and formylamino. The arylcarbonyl represented by R 2, R 3, R 4 and R 4 preferably includes phenylcarbonyl or naphthylcarbonyl. The aryl represented by R2, R3, R4 and R5 preferably includes phenyl or naphthyl. In addition, one or more hydrogen atoms in the aryl can be substituted - - by lower alkyl, halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-alkylcarbamoyl lower, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, and (N, N-di) -alkylamino lower) sulfonylamino. In accordance with the preferred embodiment of the present invention, the preferred substituent preferably includes lower alkoxy, hydroxy, formylamino and carbamoyl, particularly lower alkoxy, hydroxy and formylamino. In formula (I), R ^ is not present, or represents lower alkyl, lower cycloalkyl, or alkenyl of 2 to 4 carbon atoms, preferably lower alkyl. In addition, R is not present or represents hydrogen or a group that can hydrolyze metabolically in the body. In formula (I) when R ^ is not present, R represents hydrogen or a group that can hydrolyze metabolically in the body, and when R ^ is present, R is not present, and the compound forms an internal salt. The internal salt formed by the presence of R6 and the absence of R means the compound represented by the following formula (II): One or more of the hydrogen atoms in the lower alkyl represented. for R ^ it can be substituted by a group selected from the group consisting of halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, alkoxycarbonyl lower, formylamino, lower alkylcarbonylamino, carbamoyl, lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino (sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and aryl In addition, one or more of the hydrogen atoms in the lower cycloalkyl represented by R ^ can be substituted by a group selected from the group consists of lower alkyl, halogen, nitro, cyano, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, alkoxy lower arbonyl, formylamino, lower alkylaminocarbonylamino, carbamoyl, lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino and aryl. One or more of the hydrogen atoms in the alkenyl of 2 to 4 carbon atoms represented by R ^ can be substituted and includes a group selected from the group consisting of lower alkyl, halogen, nitro, cyano, lower cycloalkyl, alkylthio lower, lower alkoxy, hydroxy, amino, lower N-alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, ( N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfopylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino and aryl.

- - The group represented R, which can be hydrolyzed metabolically in the body of preference is ester and includes for example, lower alkylcarbonyloxy-lower alkyl, lower cycloalkylcarbonyloxy-lower alkyl, lower cycloalkylmethylcarbonyloxy-lower alkyl, lower alkenylcarbonyloxy-lower alkyl, arylcarbonyloxy-alkyl lower, tetrahydrofuranylcarbonyloxymethyl, lower alkoxy, lower alkyl, lower alkoxy-lower alkoxy-lower alkyl, arylmethyloxy-lower alkyl, arylmethyloxy-lower alkoxy-lower alkyl, lower alkyloxycarbonyloxy-lower alkyl, cycloalkyloxycarbonyloxy-lower alkyl, cycloalkylmethoxycarbonyloxy-lower alkyl, aryloxycarbonyloxy-lower alkyl, 3-phthalidyl wherein the aromatic ring can be substituted, 2- (3-phthalidylidene) ethyl wherein the aromatic ring can be substituted, 2-oxotetrahydrofuran-5-yl, 2-oxo-5-lower alkyl- 1,3-dioxolen-4-ylmethyl. The preferred example includes lower alkylcarbonyloxy-lower alkyl, lower cycloalkylcarbonyloxy-lower alkyl, lower alkyloxycarbonyloxy-lower alkyl, lower cycloalkyloxycarbonyloxy-lower alkyl, lower cycloalkylmethoxycarbonyloxy-lower alkyl, aryloxycarbonyloxy-lower alkyl, 3-phthalidyl wherein the aromatic ring may be substituted , 2. 3- - - phthalidylidene) ethyl wherein the aromatic ring can be substituted, 2-oxotetrahydrofuran-5-yl, and 2-oxo-5-lower alkyl-1,3-dioxolen-4-ylmethyl, more preferably, the pivaloyloxymethyl ester, ester of acetoxymethyl, 1- (acetoxy) ethyl ester, (1-methylcyclohexan-1-yl) carbonyloxymethyl ester, 1- (ethoxycarbonyloxy) ethyl ester, 1- (isopropoxycarbonyloxy) ethyl ester, 1- (cyclohexyloxycarbonyloxy) ester ethyl, cyclohexylcarbonyloxymethyl ester, 3-phthalidyl ester, 5-methyl-2-oxo-l, 3-dioxolen-4-ylmethyl ester, 1- [(cyclohexylmethoxy) carbonyloxy] ethyl ester, l- [ (2-methylcyclohexan-1-yl) oxycarbonyloxy] ethyl, cyclopentyloxycarbonyloxymethyl ester, (Z) -2- (3-phthalidylidene) ethyl ester, (1R, 2S, 5R) - (1) -mentyloxycarbonyloxymethyl ester, (1S, 2R, 5S) - (d) -mentyloxycarbonyloxymethyl, 1- (phenyloxycarbonyloxy) ethyl ester, phenyloxycarbonyloxymethyl ester, and 1- (cyclohexyloxycarbonyloxy) -N-propyl ester. In addition, one or more of the hydrogen atoms in the lower alkyl, lower cycloalkyl, alkenyl of 2 to 4 carbon atoms and aryl as a part of the aforementioned ester residues can be substituted by, for example, lower alkyl, halogen , nitro, cyano, lower cycloalkyl, alkylthio - - lower, lower alkoxy, hydroxy, amino, lower N-alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, ( N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, -di-lower alkylamino) sulfonylamino and aryl, preferably lower alkyl, lower alkoxy, hydroxy, formylamino, or carbamoyl. Further, when the aforementioned ester residue is 3-phthalidyl, wherein the aromatic ring can be substituted or 2- (3-phthalidylidene) ethyl wherein the aromatic ring can be substituted, the substituent includes lower alkyl, halogen, nitro, cyano , lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di-alkylaminocarbonyl lower, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-alkylamino - - lower) sulfonylamino, aryl, preferably lower alkoxy, hydroxy, formylamino, and carbamoyl. Preferred compounds of the formula (I) according to the present invention include those wherein R ^ is not present, R represents hydrogen or a group that can be hydrolyzed metabolically in the body. Compounds wherein R 6 is not present preferably include those wherein R 1 represents hydrogen or methyl. R2, R3, R4 and R ^, except that which represents the bond to position 2 of the carbapenem ring, which may be the same or different, represents, respectively, hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl can be substituted by a group selected from the group consisting of halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) - - sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and aryl, more preferably the alkyl is unsubstituted or substituted with lower alkoxy, hydroxy or formylamino. formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl. Among the above-mentioned compounds especially preferred compounds include those wherein R represents lower alkylcarbonyloxy-lower alkyl, cycloalkylcarbonyloxy-lower-lower alkyl, lower alkyloxycarbonyloxy-lower alkyl, lower cycloalkyloxycarbonyloxy-lower alkyl, cycloalkylmethoxycarbonyloxy-lower alkyl, aryloxycarbonyloxy-lower alkyl , 2-oxo-5-lower alkyl-1,3-dioxolen-3-ylmethyl, 3-phthalidyl wherein the aromatic ring can be substituted or 2- (3-phthalidylidene) ethyl wherein the aromatic ring which can be substituted is preferred .

Other preferred compounds wherein R6 is not present include those in which R1 represents methyl, R2 represents the bond at the 2-position in the carbapenem ring, R3, R4 and R5 which may be the same or different, represent, respectively, hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl can be substituted by lower alkoxy, hydroxy or formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl carbamoyl, N-lower alkylcarbamoyl, N, N-di lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl; those in which R - * - represents hydrogen, R2 represents the bond in the 2-position in the ring of carbapenem, RJ, R £ R ^, which may be the same or different represent respectively hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl can be substituted by lower alkoxy, hydroxy, or formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, alkoxyiminomethyl lower, or hydroxy inomethyl; those in which, R1 represents methyl, R3 represents the bond at position 2 in the carbapenem ring, R2, R4 and R5, which may be the same or different, respectively represent hydrogen, halogen, cyano, lower alkyl, wherein one or more than the hydrogen atoms in the alkyl may be substituted by lower alkoxy, hydroxy or formylamino, formyl, lower alkylcarbonyl, alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl; those in which R1 represents hydrogen, R3 represents the bond at position 2 in the carbapenem ring, R2, R4 and R5, which may be the same or different, respectively represent hydrogen, halogen, cyano, - - lower alkyl, wherein one or more of the hydrogen atoms in the alkyl can be substituted by lower alkoxy, hydroxy or formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di- lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl; those in which R represents hydrogen or methyl, R4 represents the bond to the 2-position in the carbapenem ring, R2, R3 and R ^, which may be the same or different, respectively represent hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl can be substituted by lower alkoxy, hydroxy or formylamino, formyl, - - lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl; and those where R! represents hydrogen or methyl, R represents the bond at position 2 on the carbapenem ring, R2, R3 and R4, which may be the same or different, represent respectively hydrogen, halogen, cyano, lower alkyl, wherein one or more of the Hydrogen atoms in the alkyl can be substituted by lower alkoxy, hydroxy or formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, - - N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl. Other preferred compounds of the formula (I) according to the present invention include those wherein R6 is present, R is not present, and the compound forms an internal salt. The compounds wherein R6 is present, and the compound forms an internal salt include more preferably those wherein R! represents hydrogen or methyl, R2, R3, R4, R5 and R ^, except that which represents the bond at position 2, in the carbapenem ring, which may be the same or different, represent respectively hydrogen, halogen, cyano, lower alkyl , wherein one or more of the alkyl hydrogen atoms can be substituted by halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N- - - lower alkylcarbamoyl, N, -di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di- lower alkylamino) sulfonylamino, and aryl, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl. Among these compounds, especially preferred compounds include those wherein R 2, R 3, R 4 and R 5, except that representing the bond at position 2 on the carbapenem ring, represent hydrogen, halogen, cyano, lower alkyl, wherein one or more than the hydrogen atoms in the alkyl can be substituted by lower alkoxy, hydroxy and formylamino, formyl, - - lower alkylcarbonyl, lower alkoxycarbonyl, aminosulphonyl, carbamoyl, lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl, and R ^ represents lower alkyl which may be substituted by a group selected from the group consisting of of lower alkoxy, hydroxy, formylamino and carbamoyl. Other preferred compounds wherein R6 is present, and the compound that forms an internal salt includes those in which R! represents methyl, R2 represents the bond to position 2 in the carbapenem ring, R3, R4 and R5 which may be the same or different, represent respectively hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl it can be substituted by lower alkoxy, hydroxy and formylamino, - formyl lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, lower N-alkylcarbamoyl N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl, and R6- represents lower alkyl which may be substituted by a group selected from the group consisting of of lower alkoxy, hydroxy, formylamino and carbamoyl; those in which R1 represents hydrogen, R2 represents the bond at position 2 in the carbapenem ring, R3, R4 and R ^, which may be the same or different, respectively represent hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl can be substituted -by means of lower alkoxy, hydroxy and formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl , or hydroxyiminomethyl, and R6 represents lower alkyl which may be substituted by a group selected from the group consisting of lower alkoxy, hydroxy, formylamino and carbamoyl; those in which R represents methyl, R3_ represents the bond to position 2 in the carbapenem ring, R2, R4 and R ^, which may be the same or different, respectively represent hydrogen, halogen, cyano, lower alkyl, wherein one or more than the hydrogen atoms in the alkyl can be substituted by lower alkoxy, hydroxy and formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl , and R6 represents lower alkyl which can be substituted by a group selected from the group consisting of lower alkoxy, hydroxy, formylamino and carbamoyl; those in which R1 represents hydrogen, R3 represents the bond to position 2 in the carbapenem ring, R2, R4 and R5, which may be the same or different, represent respectively hydrogen, halogen, cyano, lower alkyl, wherein one or more than the hydrogen atoms in the alkyl can be substituted by a group selected from the group consisting of lower alkoxy, hydroxy and formylamino, formyl, - lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl, and R ^ represents lower alkyl which may be substituted by a group selected from the group consisting of of lower alkoxy, hydroxy, formylamino and carbamoyl; those in which R1 represents hydrogen or methyl, R4 represents the bond to position 2 in the carbapenem ring, R2, R3 and R5, which may be the same or different, represent respectively hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl can be substituted by a group selected from the group consisting of lower alkoxy, hydroxy and formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl, and R ^ represents lower alkyl which can be substituted by a group selected from the group consisting of lower alkoxy, hydroxy, formylamino, and carbamoyl; and those in which R 1 represents hydrogen or methyl, R 2 represents the bond at the 2-position in the carbapenem ring, R 2, R 3 and R 4, which may be the same or different, represent, respectively, hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl can be substituted by a group selected from the group consisting of lower alkoxy, hydroxy and formylamino, formyl, - lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, lower N-alkylcarbamoyl, N, -di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl, and R6 represents lower alkyl which may be substituted by a group selected from the group consisting of lower alkoxy, hydroxy, formylamino and carbamoyl . Additional preferred compounds of the present invention include those wherein R2 or R3 represents the bond to the 2-position on the carbapenem ring. In addition, the other preferred compounds of the present invention include those wherein R ^ represents alkyl having 1-2 carbon atoms which can be substituted by carbamoyl, fluoro or hydroxy. The other preferred compounds of the present invention include those wherein R 2 represents the bond to position 2 in the carbapenem ring, all R 3, R 4 and R 2 represent hydrogen, or both R 3 and R 4 represent hydrogen and R represents a group which is selected from the group consisting of lower alkyl which can be substituted by formylamino or lower alkoxy, chloro, formyl, lower alkylcarbonyl, cyano, carbamoyl, N-lower alkylcarbamoyl and N, N-di-lower alkylaminocarbonyl. The other preferred compounds of the present invention include those in which R 2 represents the bond to the 2-position, in the carbapenem ring, and R 3 represents methyl. In addition, the other preferred compounds of the present invention include those wherein R3 represents the bond at the 2-position where the carbapenem ring, and both R2 and R4 represent a hydrogen atom and R ^ represents hydrogen or cyano. The compound represented by formula I) according to the present invention can exist as a salt, and the preferred salt is a pharmacologically acceptable salt. This salt includes, for example, inorganic salts such as lithium, sodium, potassium, calcium or magnesium salts, an ammonium salt, salts with organic bases such as triethylamine or diisopropylethylamine, salts with mineral acids such as hydrochloric acid, sulfuric acid, phosphoric acid or nitric acid, or salts with organic acids such as acetic acid, carbonic acid, citric acid, malic acid, or metal-sulphonic acid, preferably an internal salt, or sodium or potassium salt. Specific examples of the compounds of the formula (1) according to the present invention include: 1. The acid (SS, 5R, 6S) -6- (IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3-carboxylic acid; 2. Pivaloyloxymethyl (SS, 5R, 6S) -6- (IR) -l-hydroxyethyl-2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em -3-carboxylate; 3. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (6-methylimidazo [5, 1-b] thiazolium-2-yl) -l-carbapen- 2-em-3-carboxylate (internal salt); 4. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-methyl-l-carbapen-2 acid -em-3-carboxylic acid; 5. Pivaloyloxymethyl (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-methyl-1-carbapen-2 -em-3-carboxylate; 6. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (6-methylimidazo [5, 1-b] thiazolium-3-yl) -l-carbapen- 2-em-3-carboxylate (internal salt); - - 7. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylic acid; 8. Acid (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (3-methylimidazo [5, 1-b] thiazol-2-yl) -1- carbapen -2-em-3-carboxylic; 9. Pivaloyloxymethyl (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -1-methyl-2- (3-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen -2-em-3-carboxylate; 10. (SS, 5R, 6S) 2- (3,6-Dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- (IR) -1-hydroxyethyl) -l-methyl-1-carbapen- 2-em-3-carboxylate (internal salt); 11. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylic acid; 12. Pivaloyloxymethyl (5R, 6S) -6- ((IR) -l-hydroxyethyl-2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate; 13. (5R, 6S) -6- ((1R) -l-hydroxyethyl) -2- (6-methylimidazo [5, 1-b] thiazolium-3-yl) -l-carbapen-2-em-3-carboxylate ( internal salt); 14. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (6-methylimidazo [5, 1-b] thiazolium-2-yl) -l-carbapen-2-em-3- carboxylate (internal salt); 15. (SS, 5R, 6S) -2- (6-carbamoylmethylimidazo [5, lb] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2- em-3-carboxylate (internal salt); 16. Acid (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (5-methyloxy [5, 1-b] thiazol-2-yl) -l-carbapen- 2-em-3-carboxylic; 17. (SS, 5R, 6S) -2- (5, 6-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l- carbapen-2-em-3-carboxylate (internal salt); 18. Pivaloyloxymethyl (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -1-methyl-2- (5-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen -2-em-3-carboxyláte19. Acid (SS, 5R, 6S) -2- (7-chloroimidazo [5, 1-b] thiazol-2-yl) -6- ((1R-1-hydroxyethyl) -l-methyl-1-carbapen-2 em-3-carboxylic acid: 20. AcyO (SS, 5R, 6S) -6- ((IR) -l-hydroxyethyl-l-methyl-2- (2-methylimidazo [5, 1-b] thiazol-3-yl) ) -l-carbapen-2-em-3-carboxylic acid; 21. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (2-methylimidazo [5, 1-b] thiazole-) acid; 3-yl) -l-carbapen-2-em-3-carboxylic acid; 22. (1S, 5R, 6S) -2- (7-chloro-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate (internal salt); 23. Pivaloyloxymethyl (5R, 6S) -6- ((IR) -1 -hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate; 24. Acid (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylic acid; 25. Pivaloyloxymethyl (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3 -carboxylate; 26. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazol-1-yl-1-carbapen-2 sodium-3-carboxylate; 27. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazole- Pivaloyloxymethyl 2-yl) -l-carbapen-2-em-3-carboxylate; 28. (1S, 5R, 6S) -2- (6,7-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate (internal salt); 29 (5R, 6S) -2- (5,6-dimethylimidazo [5 , 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate (internal salt); 30. Acid (IS, 5R, 6S) -2- (5-formylaminomethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -1-methyl-l-carbapen-2-em-3-carboxylic acid; (SS, 5R, 6S) -2- (5-formylaminomethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2 pivaloyloxymethyl-3-carboxylate; 32. (SS, 5R, 6S) -2- (5-formylaminomethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -1-methyl-l- carbapen-2-em-3-carboxylate (internal salt); 33. Acid (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-1-carbapen 2-em-3-carboxylic acid; 34. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em- Pivaloyloxymethyl 3-carboxylate; 35. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (3-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen acid -2-em-3-carboxylic; 36. Acid (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen -2-em-3-carboxylic; 37. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3 sodium carboxylate; 38. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate from pivaloyloxymethyl; 39. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen- Pivaloyloxymethyl 2-em-3-carboxylate; - 40. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-hydroxymethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -l-methyl-l- carbapen-2-em-3-carboxylate (internal salt); 41. (5R, 6S) -2- (6,7-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em- 3-carboxylate (internal salt); 42. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3 acid -carboxylic acid; 43. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3 pivaloyloxymethyl carboxylate; 44. (5R, 6S) -2- (6,7-dimethylimidazo [5, 1-b] thiazolium-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em- 3-carboxylate (internal salt); 45. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (3-ethylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3 acid -carboxylic; 46. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (3-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3 pivaloyloxymethyl carboxylate; 47. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -l-methyl-l-carbapen-2- potassium em-3-carboxylate; - - 48. (SS, 5R, 6S) -2- (7-formylaminomethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -1-methyl-l- carbapen-2-em-3-carboxylate (internal salt); 49. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -l-methyl-l-carbapen-2- pivaloyloxymethyl em-3-carboxylate; 50. (5R, 6S) -2- (3,6-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em acid -3-carboxylic acid (internal salt); 51. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2- acetoxymethyl em-3-carboxylate; 52. 1- (Acetoxy) ethyl (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1- carboxylate methyl-l-carbapen-2-em-3-carboxylate (diastereomeric mixture); 53. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2- 3-carboxylic acid (1-methylcyclohexan-1-yl) carbonyloxymethyl ester; 54. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2- 1- (ethoxycarbonyloxy) ethyl em-3-carboxylate (diastereomeric mixture); 55. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-1-carbapen-2 1- (isopropoxycarbonyloxy) ethyl em-3-carboxylate (diastereomeric mixture); 56. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em- 3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl ester (diastereomeric mixture); 57. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2- cyclohexyloxycarbonyloxymethyl em-3-carboxylate; 58. (SS, 5R, 6S-6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em 3-phthalidyl carboxylate (diastereomeric mixture): 59. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) L-methyl-l-carbapen-2-em-3-carboxylic acid (5-methyl-2-oxo-l, 3-dioxolen-4-yl) methyl; 60. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3-carboxylic acid 1- [(cyclohexymethoxy)] carbonyloxy] ethyl (diastereomeric mixture: 61. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl 1 - [(2-methylcyclohexan-1-yl) oxycarbonyloxy] ethyl-l-carbapen-2-em-3-carboxylate (diastereomeric mixture: 62. (1S, 5R, 6S) -6- ((IR) -1 -hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3-carboxylic acid cyclopetyloxycarbonyloxymethyl ester; 63. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em- 3-carboxylate of (Z) -2- (3-phthalidilidene) ethyl; 64. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-yl. em-3-carboxylate of (IR, 2S, 5R) - (1) -mentyloxycarbonyloxymethyl; 65. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2- em-3-carboxylate (1S, 2R, 5S) - (d) -mentyloxycarbonyloxymethyl; 66. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em -3-carboxylic acid 1- (phenyloxycarbonyloxy) ethyl ester (diastereomeric mixture); 67. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em- 3-phenyloxycarbonyloxymethyl carboxylate; 68. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2- 1- (cyclohexyloxycarbonyloxy) -N-propyl em-3-carboxylate (diastereomeric mixture); 69. Acid (IS, 5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen -2-em-3-carboxylic; 70. (SS, 5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((1R-1-hydroxyethyl) -l-methyl-1-carbapen-2 pivaloyloxymethyl-3-carboxylate; 71. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -l-carbapen-2-em-3-carboxylic acid potassium ester; 72. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -l-carbapen-2-em-3-carboxylate from pivaloyloxymethyl; 73. Acid (1S, 5R, 6S) -2- (5-formylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen -2-em-3-carboxylic acid. 74. (1S, 5R, 6S) -2- (5-formylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- Pivaloyloxymethyl 2-em-3-carboxylate; 75. Acid (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-1-carbapen -2-em-3-carboxylic; 76. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -l-methyl- l-carbapen-2-em-3-carboxylate (internal salt); 77. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-7-yl) -l-methyl-l-carbapen-2- potassium em-3-carboxylate; 78. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (6-methylimidazo [5, 1-b] thiazol-7-yl) -l-methyl-1-carbapen- 2-em-3-carboxylate (internal salt); 79. (5R, 6S) -2- (7-chloroimidazo [5, 1-b] thiazol-2-yl-6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid sodium; 80. (5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em- 3-carboxylic acid: 81. (5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2- pivaloyloxymethyl em-3-carboxylate; 82. (1S, 5R, 6S) -2- (5-formyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1 -hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate (internal salt); 83. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo Pivaloyloxymethyl [5, 1-b] thiazol-7-yl) -l-methyl-carbapen-2-em-3-carboxylate; 84. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl ) -2- (7-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate of pivaloyloxymethyl; 85. (5R, 6S) -2- (7-chloro-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate (inner salt); 86. (5R, 6S) -2- (7-chloroimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of pivaloyloxymethyl; 87. (5R, 6S) -2- (6-carbamoylmethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3- carboxylate (internal salt); - 88. (SS, 5R, 6S) -2- (5,7-dimethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- Sodium 2-em-3-carboxylate; 89. (SS, 5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- Sodium 2-em-3-carboxylate; 90. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of acetoxymethyl; 91. (5R, 6S) -2- (imidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 1- (acetoxy) ethyl (diastereomeric mixture); 92. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of (1- (methylcyclohexan-1-yl) carbonyloxymethyl; 93. (5R, 6) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) - 1- (ethoxycarbonyloxy) ethyl l-carbapen-2-em-3-carboxylate (diastereomeric mixture); 94. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylic acid 1- (isopropoxycarbonyloxy) ethyl ester (diastereomeric mixture); 95. (5R, 6S) -6- ((IR) -1 -hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylic acid (cyclohexyloxycarbonyloxy) ethyl ester (diastereomeric mixture); 96. (5R, 6S) -6- ((1R-1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylic acid cyclohexyloxycarbonyloxymethyl ester; (5R, 6S) -6- ((lR) -l-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of 3 phthalidyl (diastereomeric mixture): 98. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2 3-carboxylic acid (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl ester; 99. (SS, 5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] ] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of pivaloyloxymethyl; 100. (5R, 6S) -2- (7 -formylaminomethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -l-hydroxyethyl-l-carbapen-2-em-3-carboxylate sodium; 101. (5R, 6S) -2 - (7-formylaminomethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of pivaloyloxymethyl; 102. Acid (5R , 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid; 103. (5R, 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate from pivaloyloxymethyl; - 104. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (5,6,7-methylimidazo [5, 1-b] thiazolium-2-yl) -l- carbapen-2-em-3-carboxylate (internal salt); 105. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3 sodium carboxylate; 106. (SS, 5R, 6S) -2- (7-formylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- Sodium 2-em-3-carboxylate; 107. (1S, 5R, 6S) -2- (7-formylimidazo [5, lb] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2- pivaloyloxymethyl em-3-carboxylate; 108. Acid (1S, 5R, 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR)) -1-hydroxyethyl) -l-methyl-l- carbapen-2-em-3-carboxylic; 109. (1S, 5R, 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- Pivaloyloxymethyl 2-em-3-carboxylate; 110. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazol-2-yl) -l-methyl-carbapen-2- sodium em-3-carboxylate; 111. (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazol-2-yl) -l-methyl-carbapen-2- pivaloyloxymethyl em-3-carboxylate; - 112. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate from sodium; 113. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate from pivaloyloxymethyl; 114. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3 pivaloyloxymethyl carboxylate; 115. Acid (IS, 5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen -2-em-3-carboxylic; 116. (SS, 5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- Pivaloyloxymethyl 2-em-3-carboxylate; 117. Acid (1S, 5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen -2-em-3-carboxylic; 118. (1S, 5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- Pivaloyloxymethyl 2-em-3-carboxylate; 119. (5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 acid -carboxylic; 120. Acid (5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid; - 121. (5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate from pivaloyloxymethyl; 122. (5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 acid -carboxylic; 123. (5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3- pivaloyloxymethyl carboxylate; 124. (5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 acid -carboxylic; 125. (5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 Ivaloyloxymethyl carboxylate; 126. (1S, 5R, 6S) -2- (7-ethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl- l-carbapen-2-em-3-carboxylate (internal salt); 127. Acid (5R, 6S-2- (5,7-dimethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em- 3-carboxylic acid: 128. (5R, 6S) -2- (5,7-dimethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen- Pivaloyloxymethyl 2-em-3-carboxylate 129. (5R, 6S) -2- (7-formylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) acid) -l-carbapen-2-em-3-carboxylic acid; - - 130. (5R, 6S) -2- (7-formylimidazo [5, 1-b] thiazol-3-yl) -6- ((1R) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of pivaloyloxymethyl; 131. (5R, 6S) -2- (7-ethyl-6-methylimidazo [5, 1-b] thiazolium-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2- em-3-carboxylate (internal salt); 132. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5, 6, 7-trimethylimidazo [5, 1-b] thiazolium-2-yl) -l-carbapen-2- em-3-carboxylate (internal salt); 133. (SS, 5R, 6S) -2- (7-acetylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- Sodium 2-em-3-carboxylate; 134. (1S, 5R, 6S) -2- (7-acetylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- Pivaloyloxymethyl 2-em-3-carboxylate; 135. (5R, 6S) -2- (7-Acetylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -2-hydroxyethyl) -l-carbapen-2-em-3 acid -carboxylic; 136. Acid (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxyiminomethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-1-carbapen -2-em-3-carboxylic (geometric isomer derived from a high polar oxime isomer as a raw material); 137. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl acid ] -l-carbapen-2-em-3-carboxylic acid; 138. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -l pivaloyloxymethylcarbapene-2-em-3-carboxylate; 139. (SS, 5R, 6S) -2- [7- (N, N-dimethylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l sodium methyl carbapen-2-em-3-carboxylate; 140. (1S, 5R, 6S) -2- [7- (N, N-dimethylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -6- ((IR) -1-hydroxyethyl) -l pivaloyloxymethyl-methyl-l-carbapen-2-em-3-carboxylate; 141. (1S, 5R, 6S) -2- [7- (N, N-dimethylcarbamoyl) imidazo [5, 1-b] thiazol-3-yl] -6- ((IR) -1-hydroxyethyl) -l sodium-methyl-l-carbapen-2-em-3-carboxylate; 142. (1S, 5R, 6S) -2-] 7- (N, N-dimethylcarbamoyl) imidazo [5, 1-b] thiazol-3-yl] -6- ((IR) -1-hydroxyethyl) -l pivaloyloxymethyl-methyl-l-carbapen-2-em-3-carboxylate; 143. (5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 acid -carboxylic; 144. (5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 pivaloyloxymethyl carboxylate; 145. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -l-carbapen- 2-em-3-carboxylic; - - 146. (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -l-carbapen-2-em Pivaloyloxymethyl carboxylate; 147. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxyiminomethyl-idazo [5, 1-b] thiazol-2-yl) -1-methyl-1-carbapen -2-em-3-carboxylate sodium (geometric isomer derived from high polar oxime unisomer as a raw material); 148. (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxyiminomethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-1-carbapen- Pivaloyloxymethyl 2-em-3-carboxylate (geometric isomer derived from a high isomer of polar oxime as a raw material).

Preparation of the Compounds The compounds according to the present invention can be prepared by a variety of methods. The preferred preparation methods are shown below.

Process (1) First, the compound of the formula (1) according to the present invention can be prepared according to the following reaction project. - - wherein R1, R2, R3, R4 and R5 have the same meaning as defined in formula (I), R7 represents hydrogen or a hydroxyl protecting group such as t-butyldimethylsilyl, trimethylsilyl, triethylsilyl, 4-nitrobenzyloxycarbonyl, 4- methoxybenzyloxycarbonyl, R8 represents a carboxyl protecting group such as 4-nitrobenzyl, 4-methoxybenzyl, diphenylmethyl, t-butyldimethylsilyl, - R ^ represents lower alkyl, preferably n-butyl and methyl. The compound of the formula (III) can be prepared by the regular method, and the tin compound of the formula (V) can be prepared by a method which will be described below. In the first step, the compound of the formula (II) can be converted to the compound of the formula (IV) by the following method. The compound (IV) can be prepared by reacting the compound of the formula (III) with one (1) equivalent or an excessive amount of the anhydrous trifluoromethanesulfonic acid, in the presence of an organic base, preferably diisopropylethylamine in an amount of one (1) equivalent or an excessive amount with respect to the anhydrous trifluoromethanesulfonic acid in a solvent inert such as acetonitrile, tetrahydrofuran, dichloromethane and toluene, and the mixed solvent thereof at a temperature of -50 ° C - + 50 ° C for 10 minutes - 24 hours, and then subjecting the reaction mixture to the usual purification procedure. In the second step, the compound of the formula (IV) can be converted to the compound of the formula (VI) by the following method. The compound of the formula (VI) can be prepared by reacting the compound of the formula (IV) with an equivalent (1) or an amount - exceedance of the compound of the formula (V) in the presence of 0.001 to 1 equivalent of a palladium catalyst such as tetrakis (triphenylphosphine) palladium (O), tris (dibenzylideneacetone) -dipaladium (O), or a tris (dibenzylidene ketone) adduct dipalladium (O) -chloroform, from 0.01 to 1 equivalent of a phosphine coordinating group, such as triphenylphosphine, tris-2-furylphosphine, or tri-2-thienylphosphine, tris (2, 4, 6-trimethoxyphenyl) phosphine, and 1 to 10 equivalents of an additive such as zinc chloride, lithium chloride, or cesium fluoride alone in combination therewith in an inert solvent such as tetrahydrofuran, dimethoxyethane, dioxane, acetonitrile, acetone, ethanol, dimethylsulfoxide, sulfolane, N , N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidinone, or hexamethylphosphoric triamide, or a mixed solvent thereof at 0 ° C-100 ° C for 10 minutes-7 days then subjecting the reaction mixture to a post-reaction mixture. regular treatment Then, the protecting groups R7 and R8 in the compound of the formula (VI) can be removed by the deprotection reaction in one step or multiple steps, depending on the classes of protecting groups to obtain the compound of the formula (I) in accordance with the present invention. The deprotection reactions, which depend on the classes of protecting groups R7 and R8 used, can be carried out according to the usual methods generally known in the art. When one or both of the protecting groups can be removed under the acidic condition, a mineral acid such as hydrochloric acid, an organic acid such as oxalic acid, acetic acid or citric acid, or a Lewis acid such as sodium chloride is used. aluminum. When the protecting groups are removed under a reducing condition, catalytic reduction is used with a variety of catalysts, or a metal reducing agent such as zinc or iron. When R7 is a silyl type protecting group such as a t-butyldimethylsilyl group, a trimethylsilyl group or a triethylsilyl group, it can be easily removed with the use of a fluoride ion reagent such as tetrabutylammonium fluoride. When R7 is an alioxycarbonyl group and R8 is an allyl group, the protecting groups can be easily removed with the use of a variety of palladium complex such as tetrakis (triphenylphosphine) palladium (O).

Process (2) The compound of the formula (I) according to the present invention, wherein R ^ is not present, can also be prepared according to the following reaction.

Additive and Heat - - wherein R-, R2, R3, R4 and R ^ have the same meanings as defined in formula (I), R ° has the same meaning as defined above, R represents a hydroxyl protecting group such as t-butyldimethylsilyl, trimethylsilyl, triethylsilyl or 4-nitrobenzyloxycarbonyl, R ^ represents lower alkylcarbonyloxy, such as t-butylcarbonyloxy, secondary butylcarbonyloxy, isopropylcarbonyloxy, arylcarbonyloxy such as benzenecarbonyloxy, 2-chlorobenzenecarbonyloxy, arylthio, preferably 2-pyridyldithio, M represents Li, MgCl, MgBr or Mgl. The compound of the formula (VIII) in the project can be prepared by the method described in PCT / JP97 / 04270. In the first step, the compound of the formula (IX) can be converted into the compound of the formula (X) by the following method. When the reagent used is an acid halide such as pivaloyl chloride or 2-chlorobenzoyl chloride, the compound of the formula (IX) can be reacted with an equivalent (1) or an excessive amount of the acid halide in the presence of an organic base such as triethylamine, diisopropylethylamine, - - pyridine, 2,6-lutidine, diazabicyclo [2, 2, 2] undecene in a ratio of one (1) equivalent or an excessive amount with respect to the acid halide in an inert solvent such as acetonitrile, THF, dichloromethane or toluene, or a third solvent thereof at a temperature of -50 ° C - + 50 ° C for 10 minutes - 24 hours, then subjecting to regular after-treatment to provide the compound of the formula (X). When the reagent used is a thiol esterification agent of 2,2'-dipyridyl disulfide, the compound of the formula (IX) can be reacted with one (1) equivalent or an excessive amount of the thiol esterification agent. in the presence of a phosphine compound such as triphenylphosphine or tributylphosphine in a ratio of one (1) equivalent to an excessive amount with respect to the thiol esterification agent in an inert solvent such as acetonitrile, THF, dichloromethane or toluene, or a solvent mixing thereof at a temperature of -50 ° C - + 50 ° C for 10 minutes - 24 hours, and then undergoing regular after-treatment to provide the compound of the formula (X). In the second step, the compound of the formula (X) can be converted to the compound of the formula (XI) by the following method. The compound of the formula - - (XI) can be prepared by adding an equivalent (1) or an excessive amount of a solution of the compound of the formula (X) in an inert solvent such as diethyl ether or THF to the compound of the formula (VIII) dissolved suspended in a inert solvent such as diethyl ether or THF, or by adding the compound of the formula (VIII) in an amount of less than one equivalent (1) dissolved or suspended in an inert solvent such as diethyl ether or THF to the compound of the formula (X) dissolved in an inert solvent such as diethyl ether or THF, by reacting the mixture at a temperature of -50 ° C - + 50 ° C for 10 minutes -24 hours, and undergoing regular post-treatment. Then, in the third step, the compound of the formula (XI) can be converted into the compound of the formula (XII) for example by the following method. The compound of the formula (XII) can be prepared by reacting the compound of the formula (XI) "dissolved in an inert solvent such as benzene, toluene, xylene, THF or dioxane with a catalytic amount of an additive preferably hydroquinone at a temperature from room temperature to the reflux temperature for 10 minutes - 24 hours, and undergoing regular after-treatment The protective groups R8 and R1-1- in the compound of the formula (VI) can be removed by the reaction - - of deprotection in one or more steps depending on the kinds of protecting groups to obtain the compound of the formula (I) according to the present invention. Deprotection reactions that depend on the classes of protecting groups R8 and Rn used can be carried out according to the usual methods generally known in the art. When either or both of the protecting groups can be removed under the acidic condition, a mineral acid such as hydrochloric acid, an organic acid such as oxalic acid, acetic acid or citric acid, or a Lewis acid such as chloride is used. of aluminum. When the protecting groups are removed under a reducing condition, a catalytic reduction with a variety of catalysts, or a metallic reducing agent, for example zinc or iron, is used. When R is a silyl type protecting group such as the t-butyldimethylsilyl group, a trimethylsilyl group or a triethylsilyl group, can be easily removed with the use of a fluorine ion reagent such as tetrabutylammonium fluoride. When RÜ is an alioxycarbonyl group and R 8 is an allyl group, the protecting groups can be easily removed with the use of a variety of palladium complex such as tetrakis (triphenylphosphine) palladium (O). The compound of formula (I) obtained in this way can be isolated and purified by crystallization or by chromatography with a high-porosity nonionic macro resin, gel filtration with Sephadex or the like, or silica gel column chromatography of reverse phase.

Process (3) The compounds of the formula (I) wherein R represents a hydrolysable ester in organisms can be prepared by converting the compounds represented by the formula (I) into the ester derivatives. wherein R1, R2, R3, R4, R and R have the same meanings as defined in formula (I). X represents an output group such as Cl, Br, I, -OS02CF3, -OSO2CH3, or -OS02PhCH3. Ester derivatives can be prepared by reacting the compound of the formula "(I) with an alkyl halide R10-X in the presence of one (1) equivalent or an excessive amount of base at a temperature of -70 ° C - - + 50 ° C, preferably from -30 ° C to + 20 ° C for 10 minutes -24 hours. The base usable in the reaction includes, for example, organic bases such as diisopropylethylamine, diazabicyclo [2, 2, 2] undecene and 2,6-lutidine, and inorganic bases such as sodium hydroxide, potassium hydroxide, hydrogen carbonate sodium, potassium hydrogen carbonate, sodium carbonate, potassium carbonate and cesium carbonate. The alkyl halide R10-X includes, for example, pivaloyloxymethyl iodide, 1- (pivaloyloxy) ethyl iodide, isobutyryloxymethyl iodide, 1- (isobutyryloxy) ethyl iodide, acetoxymethyl iodide, 1- (acetoxy) ethyl iodide, iodide. of (1-methylcyclohexan-1-yl) carbonyloxymethyl, 1- (cyclohexyloxycarbonyloxy) ethyl iodide, 1- [(cyclohexylmethoxy) carbonyloxy] ethyl iodide, 1- (ethoxycarbonyloxy) ethyl iodide, cyclohexyloxycarbonyloxymethyl iodide, 1-iodide [(2-methylcyclohexan-1-yl) oxycarbonyloxy] ethyl, cyclopentyloxycarbonyloxymethyl iodide, 1- (isopropyloxycarbonyloxy) ethyl iodide, (IR, 2S, 5R) - (1) -mentyloxycarbonyloxymethyl iodide, (1S, 2R, 5S) - (d) -mentyloxycarbonyloxymethyl, 1- (phenyloxycarbonyloxy) ethyl iodide, phenyloxycarbonyloxymethyl iodide, 1-6-iodide (cyclohexyloxycarbonyloxy) -N-propyl, (5-methyl-2-oxo-l, 3-dioxolen-4-yl) methyl bromide, 3-phthalidyl bromide, (Z) -2- (3-phthalidylidene) bromide ethyl, and the like. The inert solvent usable in the reaction includes N, N-dimethylphoramide, N, N-dimethylacetamide, N, N-diethylformamide, N, N-diethylacetamide, N-methylpyrrolidinone, N, N-dimethylimidazolidinone, dimethyl sulfoxide, sulfolane, acetonitrile, acetone, ethyl acetate, tetrahydrofuran, 1,4-dioxane, diethyl ether, anisole, dichloromethane, 1,2-dichloroethane, chloroform, toluene, benzene, triaxy-hexamethylphosphoric acid, methanol and ethanol. The ester derivatives obtained in this way can be isolated and purified by precipitation, crystallization, gel filtration with Sephadex, or silica gel chromatography. Process 4 The compound represented by the formula (I) wherein R6 is present can be prepared preferably by the following reaction.

(V!) - - Vulnerability wherein R1, R2, R3, R4, R5 and R6 have the same meanings as defined in formula (I). R7 and R8 have the same meanings as defined above, and represents an output group such as Cl, Br, I, -OS02CF3, -0S02CH3 or -OS02PhCH3. The compound of the formula (VI) can be prepared according to the method described above. In the first step, the compound of the formula (VI) can be converted to the compound of the formula (VII) by the following method. The compound of the formula (VII) can be prepared by reacting the compound of the formula (VI) with one equivalent (1) or an excessive amount of the compound R - -Y in the absence or presence of an inert solvent such as acetonitrile, acetone , tetrahydrofuran, dichloromethane, toluene, N, N-dimethylformamide, N, N-dimethylacetamide or dimethylsulfoxide - - minutes - 1 week, and undergoes the usual post-treatment. The compound of the formula R ^ -Y includes, for example, methyl iodide, carbamoylmethyl iodide, 2-fluoroethyl trifluoromethanesulfonate, 2-hydroxyethyltrifluoromethanesulfonate, cyclopropylmethyl bromide., and methoxymethyl iodide. Then, the protecting groups R7 and R8 in the compound of the formula (VII) can be removed by the deprotection reaction in one step or multiple steps, depending on the classes of the protecting groups to obtain the compound of the formula (I) in accordance with the present invention. The deprotection reactions, which depend on the classes of the protecting groups R7 and R8 used, can be carried out in accordance with usual methods generally known in the art. When one or both of the protecting groups can be removed under the acidic condition, a mineral acid such as hydrochloric acid, an organic acid such as oxalic acid, acetic acid or citric acid, or a Lewis acid such as aluminum chloride is the one it's used. When the protecting groups are removed under a reducing condition, the catalytic reduction can be used with a variety of catalysts or a metal reducing agent such as zinc or iron. When R7 is a silyl type protecting group such as t-butyldimethylsilyl, tri-ethylsilyl or triethylsilyl, they can be easily removed with the use of a fluoro-ion reagent such as tetrabutylammonium fluoride. When R7 is alioxycarbonyl and R8 is allyl, the protecting groups can be easily removed with the use of a variety of palladium complexes such as tetrakis (triphenylphosphine) palladium (O). The compound of the formula (I) obtained in this way can be isolated and purified by crystallization or by chromatography with a non-ionic acro-highly porous resin, gel filtration with Sephadex or the like, or phase silica gel column chromatography. reverse.

Process (5) A compound of the formula (V) used in the reaction described above can be prepared by the following method.

(Vlü) (V) where R2, R3, R4 and R-0 are either one of which is Mor R93SN, and the remaining three that can be equal or - different have the same meanings as defined in formula (I), that is, they represent hydrogen, halogen, nitro, cyano, lower alkyl, lower cycloalkyl, lower alkylthio, alkenyl of 2 to 4 carbon atoms, formyl, lower alkylcarbonyl , arylcarbonyl, aryl, R9 represents lower alkyl, preferably N-butyl or methyl, M represents Li, MgCl, MgBr or Mgl, and Z represents Cl, Br, I or -OS02CF3. ~~~~ The compound of the formula (VIII) used can be prepared according to the method described in Japanese Patent Application Number 313922/1996. The compound of the formula (VIII) can be converted to the compound of the formula (V) by the following method. The compound of the formula (V) can be prepared by reacting the compound of the formula (VIII) in an inert solvent, such as tetrahydrofuran, diethyl ether, 1,4-dioxane, anisole, dimethoxyethane, dichloromethane or toluene alone or in combination thereof with R93SNZ in a ratio of one (1) equivalent or an amount excessive with respect to the compound of the formula (VIII), at a temperature of -100 ° C to + 50 ° C for 15 minutes - 24 hours, and then undergo the usual post-treatment.

- - The compound of the formula (I) obtained in this way can be isolated and purified by crystallization or by chromatography with a highly porous non-ionic macro resin, gel filtration with Sephadex or the like, or phase silica gel column chromatography. reverse.

Applications of the compound / pharmaceutical composition The compound according to the present invention has broad and intense anti-microbial activities against Gram-positive and Gram-negative bacteria, and exhibits intense anti-microbial activities against MRSA, PRSP, enterococci, influenza and bacteria that they produce ß-lactamase likewise. In addition, it has low toxicity and is stable to DHP-1. Therefore, the compound according to the present invention can be used for the treatment of infections caused by different pathogenic bacteria in animals, including humans. The compound of the formula (I) wherein R represents a hydrolysable group in especially organisms, can be advantageously administered orally due to its excellent oral absorption property. - The pharmaceutical composition according to the present invention and a pharmacologically acceptable salt and - Ester thereof as an effective ingredient can be administered orally or parenterally by the routes of administration including intravenous injection, intramuscular or subcutaneous injection, rectal or percutaneous administration to humans and other animals. In this manner, the pharmaceutical composition comprising the compound according to the present invention as an effective ingredient can be formed into appropriate dosage forms, depending on their routes of administration, and prepared specifically especially in any of the preparation forms. including injections, such as intravenous injection and intramuscular injection, preparations for oral administration such as capsules, pills, granules, powder, pills, particulate materials, troches, preparations for rectal administration, and fatty suppositories. These preparations can be prepared by the usual methods with excipients generally used as fillers or fillers, bonding agents, wetting agents, disintegrants, surfactants, lubricants, dispersants, stabilizers, storage agents, dissolution aids, preservatives, flavor agents, analgesic agents, stabilizing agentsand similar These non-toxic additives which can be used include for example lactose, fructose, glucose, starch, gelatin, magnesium carbonate, synthetic magnesium silicate, talc, magnesium stearate, methylcellulose or a salt thereof, gum arabic, polyethylene glycol, syrup, petrolatum, glycerol, ethanol, propylene glycol, citric acid, sodium chloride, sodium sulfite, sodium phosphate, and the like. The dosage amount is appropriately determined in consideration of the dosage route, and the age, sex and condition of a patient, and the preparation can be administered for the treatment of infections usually in an amount of about 25 milligrams to 2000 milligrams. preferably from 50 milligrams to 1000 milligrams per day for an adult in one or several servings.

Example The present invention is now described with reference to the Examples and Synthetic Examples, but is not limited thereto.

Preparation 1 3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole 2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole - A solution of imidazo [5, 1-b] thiazole (248 milligrams) in anhydrous THF (4 milliliters was cooled to -78 ° C under an argon atmosphere.) A solution of 1.6 N lithium n-butyl was added dropwise. in n-hexane (1.31 milliliters) at an internal temperature of -60 ° C to -55 ° C. The reaction was stirred at the same temperature for 1 hour, and further stirred for 40 minutes, during which the mixture was left The reaction mixture was diluted with 50 milliliters of an aqueous, semi-saturated ammonium chloride solution and extracted with 50 milliliters of diethyl ether. The organic layer was dried over anhydrous magnesium sulfate, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure The residue obtained in this way was purified by column chromatography on silica gel (toluene: ethyl acetate = 1: 1). 3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole in an amount of 221 milligrams of the fraction having Rf = 0.7 Nuclear Magnetic Resonance (CDCI3) 5: 0.90 (9H, t, J = 7.1 Hz), 1.22 (6H, m), 1.34 (6H,), 1.59 (6H, m), 6.63 (HI, s), 7.10 (ÍH, s), 7.92 (1H, s). 2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole was obtained in an amount of 270 milligrams of the fraction having Rf = 0.5.

- Nuclear Magnetic Resonance (CDC13) d: 0.92 (3H, t, J = 7.3 Hz), 1.16 (2H, m), 1.35 (2H, m), 1.58 (2H, m), 7.02 (1H, s), 7.17 ( ÍH, s), 7.95 (ÍH, s).

Preparation 2 2- (tri-n-butylstannyl) -3-methylimidazo [5, 1-b] thiazole A solution of 3-methylimidazo [5, 1-b] thiazole (513.2 milligrams) in anhydrous THF (8 milliliters) was cooled at -78 ° C under an argon atmosphere, and a 1.6 N lithium solution of n-butyl in n-hexane was added dropwise. (2.47 milliliters). After the reaction was stirred at the same temperature for 1 hour, 1.06 milliliters of tri-n-butylstannyl chloride was added, and the mixture was further stirred at the same temperature for 1 hour and then for 30 minutes during which time the The mixture was allowed to warm to room temperature. The reaction mixture was diluted with 50-ilyls of a half-saturated aqueous ammonium chloride solution, and extracted with 50 milliliters diethyl ether. The organic layer was dried through anhydrous magnesium sulfate, and the solvent was then removed under reduced pressure. The residue obtained in this way was purified by column chromatography on silica gel (hexane: ethyl acetate = 1: 1) to give 2- (tri-n-butylstannyl) -3-methylimidazo [5, 1-b] thiazole in a yield of 1.44 grams.

- - Nuclear Magnetic Resonance d: 0.84 (9H, t, J = 7.3Hz), 1.10 (6H, m), 1.28 (6H, m), 1.50 (6H, m), 2.31 (3H, s), 6.96 (ÍH, s ), 7.75 (ÍH, s). MS (PB (CH4-CI)): 429 (M + + H) Preparation 3 5-Methyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole A solution of 5-methylimidazo [5, 1-b] thiazole (1.10 grams) in THF (16 milliliters) was cooled at -78 ° C under the argon atmosphere, and a 1.6 N lithium solution of n-butyl in n-hexane (5.24 milliliters) was added dropwise thereto at an internal temperature of = 70 ° C to -65 ° C. After the mixture was stirred at the same temperature for 1 hour, 2.40 milliliters of ri-n-butylstannyl chloride was added and the mixture was stirred at the same temperature for 1 hour, and then for an additional two hours during which time the The mixture was allowed to warm to -40 ° C. The reaction mixture was diluted with 100 milliliters of a semi-saturated aqueous ammonium chloride solution and extracted with 100 milliliters of diethyl ether. The organic layer was dried through anhydrous magnesium sulfate, and the solvent was then removed under reduced pressure. The residue obtained in this way was purified by column chromatography on silica gel (toluene: ethyl acetate = 1: 1) to give the title compound in a yield of 2.23 grams. Nuclear Magnetic Resonance (CDCI3) d: 0.92 (9H, t, J = 7.2 Hz), 1.15 (6H, m), 1.36 (6H, m), 1.57 (6H,), 2.57 (3H, s), 6.88 (1H , s), 6.93 (1H, s).

Preparation 4 7-chloro-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole and 7-chloro-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole a) , 7-dichloroimidazo [5, 1-b] thiazole, 5-chloroimidazo [5, 1-b] thiazole and 7-chloroimidazo [5, 1-b] thiazole _ To a solution of imidazo [5, 1-b] thiazole (18.624 grams) in dichloromethane (450 milliliters) was added 20.030 grams of N-chlorosuccinimide, the mixture was heated in a bath at a temperature of 60 ° to 65 ° C for 1 hour. After cooling in air, the insoluble materials were removed by filtration and the solvent was removed under reduced pressure. The residue obtained in this way was dissolved in 3.0 liters of ethyl acetate, and washed three times with 3.0 liters of distilled water. After the organic layer was dried through anhydrous magnesium sulfate and the magnesium sulfate was removed by filtration, the solvent was removed under reduced pressure. The solid product obtained in this way was purified by column chromatography on silica gel (acetate - - of ethyl) to provide 2.020 grams of 5,7-dichloroimidazo [5, 1-b] thiazole as a pale brown powder of the fraction of Rf = 0.85. Nuclear Magnetic Resonance (CDCI3) d: 6.91 (1H, d, J = 4.3 Hz), 7.28 (1H, d, J = 4.3 Hz) MS (Mass Spectrum) (TSP): 195 (M + + 3H), 193 ( M + + H). In addition, 5-chloroimidazo [5, 1-b] thiazole was obtained in a pale brown powder (2550 grams) of the fraction of Rf = 0. 7. Nuclear Magnetic Resonance (CDCI3) d: 6.87 (ÍH, d, J = 4. 3 Hz), 7.02 (HH, s), 7.29 (1H, d, J = 4.3 Hz). MS (TSP): 161 (M + + 3 H), 159 (M + + H). In addition, 7-chloroimidazo [5, 1-b] thiazole was obtained as a yellowish white plate (13.384 grams) of the fraction of Rf = 0.5. Nuclear Magnetic Resonance (CDCI3) d: 6.87 (ÍH, d, J = 4. 2 Hz), 7.38 (ÍH, d, J = 4.2 Hz), 7.87 (1H, s). MS (TSP): 161 (M + + 3 H), 159 (M + H). b) 7-chloro-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole and 7-chloro-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole at 40 milliliters of THF were added 6.25 milliliters of a solution of 1.6 N lithium n-butyl in n-hexane, and the mixture was cooled to -78 ° C. A solution of 7-chloroimidazo [5, 1-b] thiazole (1.59 grams) in THF (40 milliliters) was added dropwise at an internal temperature of - - -40 ° C. Then the reaction mixture was stirred for 1 hour through which time the temperature was raised to 0 ° C, and 3.43 milliliters of tri-n-butylstannyl chloride was added and the mixture was stirred for 2 hours during which the temperature rose to room temperature. The reaction mixture was diluted with 300 milliliters of a semi-saturated aqueous ammonium chloride solution and extracted with 300 milliliters of diethyl ether. The organic layer was dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained in this way was purified by column chromatography on silica gel (hexane: ethyl acetate = 20: 1-10: 1-5: 1-3: 1). As a low polar component, 7-chloro-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole was obtained in a yield of 362 milligrams. Nuclear Magnetic Resonance (CDCI3) d: 0.90 (9H, t, J = 7. 3 Hz), 1.22 (6H, m), 1.34 (6H, m), 1.54 (6H, m), 6.63 (HH, s), 7.77 (HH, s). In addition, as a high polar component, we obtained 7-chloro-2- (tri-n-butyl-stanyl) imidazo [5, 1-b] thiazole in a yield of 2.78 grams. Nuclear Magnetic Resonance (CDCI3) d: 0.92 (9H, t, J = 7. 4 Hz), 1.16 (6H, m), 1.35 (6H, m), 1.58 (6H, m), 7.11 (1H, s), 7.80 (H, s).

Preparation 5 2-methyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole The title compound was obtained in an amount of 2.67 grams from 2.20 grams of 2-methylimidazo [5, 1- b] thiazole in the same manner as in Preparation 3. Nuclear Magnetic Resonance (CDCI3) d: 0.90 (9H, t, J = 7.2 Hz), 1.24 (6H, m), 1.35 (6H, m), 1.54 (6H , m), 2.35 (3H, s), 7.00 (H, s), 7.83 (H, s).

Preparation 6 5-formylaminomethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole A solution of 906 milligrams of 5-formylaminommethylimidazo [5, 1-b] thiazole in a mixed solvent of 30 milliliters of THF and 6 milliliters of HMPA was cooled to -78 ° C under the argon atmosphere, and 10.9 milliliters of a solution of 1.6 N lithium n-butyl / n-hexane was added per drop at an internal temperature of -70 ° C to -65 ° C. After the reaction mixture was stirred at the same temperature for 1 hour, 1.63 milliliters of tri-n-butylstannyl chloride was added, and the mixture was further stirred at the same temperature for 1 hour and for 2 hours through which the temperature rose to 0 ° C. 100 milliliters of a semi-saturated aqueous ammonium chloride solution was added to the reaction mixture and extracted with 100 milliliters of diethyl ether. The organic layer was dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained in this way was purified by column chromatography on silica gel (hexane: ethyl acetate = 1: 2) to give the title compound in an amount of 1.59 grams. Nuclear Magnetic Resonance (CDCI3) d: 0.92 (9H, t, J = 7.4 Hz), 1.16 (6H, m), 1.35 (6H, m), 1.57 (6H, m), 4.74 (2H, d, J = 6.1 Hz), 6.90 (ÍH, s), 7.22 (ÍH, broad s), 7.37 (ÍH, s), 8.28 (ÍH, s).

Preparation 7 3- (t-Butyldimethylsilyloxy) methyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole a) 3- (butyldimethylsilyloxy) methylimidazo [5, 1-b] thiazole To a solution cooled in 3.39 grams of 3-hydroxymethylimidazo [5, 1-b] thiazole in 22 milliliters of DMF was added 1.95 grams of imidazole and 3.81 grams of t-butyldimethylsilyl chloride. After the reaction mixture was reacted at room temperature for 6 hours, it was diluted with 150 milliliters of ethyl acetate, and washed three times with a saline solution. The organic layer was dried through magnesium sulfate - Anhydrous, the solvent was removed under reduced pressure to provide 5.83 grams of 3- (t-butyldimethylsilyloxy) methylimidazo [5, 1-b] thiazole. Nuclear Magnetic Resonance (CDCI3) d: 0.09 (6H, s), 0.88 (9H, s), 4.76 (2H, s), 6.60 (H, s), 7.07 (H, s), 8.02 (ÍH, s). b) 3- (t-butyldimethylsilyloxy) methyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole The title compound was obtained in a quantity of 1.01 grams of 548 milligrams of 3- (t- butyldimethylsilyloxy) methylimidazo [5, 1-b] thiazole, in the same manner as in Preparation 3. Nuclear Magnetic Resonance (CDCI3) d: 0.15 (6H, s), 0.91 (9H, t, J = 7.4 Hz), 0.93 (9H, s), 1.16 (6H, m), 1.34 (6H, m), 1.56 (6H, m), 4.68 (2H, s), 7.01 (ÍH, s), 8.02 (ÍH, s).

Preparation 8 5- (t-Butyldimethylsilyloxy) methyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole a) 5- (t-butyldimethylsilyloxy) methylimidazo [5, 1-b] thiazole The 5- (t-butyldimethylsilyloxy) methylimidazo [5, 1-b] thiazole in an amount of 2.71 grams of 1. 54 grams of 5-hydroxymethylimidazo [5, 1-b] thiazole in the same manner as in Preparation 7-a).

Nuclear Magnetic Resonance (CDC13) d: 0.06 (6H, s), 0.89 (9H, s), 4.97 (2H, s), 6.79 (IH, d, J = 4.3 Hz), 6.97 (1H, s), 7.55 ( ÍH, d, J = 4.3 Hz). b) 5- (t-butyldimethylsilyloxy) methyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole The title compound was obtained in an amount of 2.60 grams from 1.34 grams of 5- ( t-butyldimethylsilyloxy) methylimidazo [5, 1-b] thiazole in the same manner as in Preparation 3. Nuclear Magnetic Resonance (CDC1) d: 0.05 (6H, s), 0.89 (9H, s), 0.91 (9H, t , J = 7.1 Hz), 1.14 (6H, m), 1.35 (6H, m), 1.57 (6H,), 4.96 (2H, s), 6.90 (HH, s), 7.32 (HH, s).

Preparation 9 5-carbamoyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole and 5-carbamoyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. -carbamoyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole as a low polar component in an amount of 114 milligrams of 167 milligrams of 5-carbamoylimidazo [5, 1-b] thiazole thereof How to prepare 6. Nuclear Magnetic Resonance (CDCI3) d: 0.87 (9H, t, J = 7.4 Hz), 1.12 (6H, m), 1.32 (6H, m), 1.53 (6H, m), 5.23 (HI) , broad) 6.88 (ÍH, s), 6.95 (1H, broad, 7.19 (ÍH, s).

- In addition, 5-carbamoyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole was obtained as a high polar component in an amount of 211 milligrams. Nuclear Magnetic Resonance (CDC13) d: 0.91 (9H, t, J = 7.4 Hz), 1.18 (6H, m), 1.35 (6H, m), 1.57 (6H, m), 5.40 (1H, s broad), 6.90 (ÍH, broad), 7.12 (ÍH, s), 8.12 (ÍH, s).

Preparation 10 7-carbamoyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole and 7-carbamoyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole a) 7 -carboxyimidazo [5, 1-b] thiazole To an ice-cooled solution of 5.00 grams of 7-iodoimidazo [5, 1-b] thiazole in 150 milliliters of THF under the argon atmosphere were added 20 milliliters of a solution per drop. of 1.0 N of N-ethylmagnesium bromide in THF. After the reaction mixture was stirred at room temperature for 30 minutes, it was further stirred under bubbling of carbon dioxide gas at room temperature for 20 hours. The reaction mixture was concentrated under reduced pressure, diluted with 100 nililiters of water, and adjusted to a pH of 6.5 with 1 N HCl. Purified with DIAION HP-20 (5 to 10 percent methanolic water) to provide 3.31 grams of 7-carbaxylimidazo [5, 1-b] thiazole.

- Nuclear Magnetic Resonance (DMSO-dg) d: 7.25 (1H, d, J = 4.1 Hz), 7.86 (ΔH, d, J = 4.1 Hz), 8.09 (ΔH, s). b) 7-carbamoylimidazo [5, 1-b] thiazole To a solution of 2.46 grams of 7-carboxyimidazo [5, 1-b] thiazole in 100 milliliters of DMF was added 5.62 grams of 1-hydroxybenzo-triazole and 5.62 grams of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, and the mixture was stirred at room temperature for 1.5 hours, diluted with 15 milliliters of a 3.5 N ammonia solution in ethanol, and further stirred at room temperature for 20 hours. The reaction mixture was concentrated under reduced pressure, diluted with 200 milliliter of an aqueous solution of potassium carbonate to adjust the pH to 10.4 and extracted ten times with dichloromethane. The organic layer was dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained in this way was purified by silica gel column chromatography (dichloromethane: methanol = 30: 1) to give 7-carbamoylimidazo [5, 1-b] thiazole, in a yield of 1.83 grams. Nuclear Magnetic Resonance (CDCI3) d: 5.36 (1H, broad s), 6.77 (1H, broad s, 7.04 (HH, d, J = 4.1), 7.50 (HH, d, J = 4.1 Hz). s). - - c) 7-carbamoyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole and 7-carbamoyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. -carbamoyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole as a low polar component at an amount of 360 milligrams from 1.23 grams of 7-carbamoyl-idazo [5, 1-b] thiazole in the same way as Preparation 6. Nuclear Magnetic Resonance (CDCI3) d: 0.90 (9H, t, J = 7.3 Hz), 1.24 (6H, m), 1.35 (6H, m), 1.55 (6H, m), 5.38 (1H, broad), 6.78 (wide), 6.82 (HH, s), 7.83 (1H, s). In addition, 7-carbamoyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole was obtained as a high polar component in an amount of 420 milligrams. Nuclear Magnetic Resonance (CDCI3) d: 0.91 (9H, t, J = 7.2 Hz), 1.17 (6H, m), 1.35 (6H, m), 1.58 (6.H,), 5.35 (ÍH, s broad), 6.75 (ÍH, broad) 7.23 (ÍH, s), 7.88 (ÍH, s).

Preparation 11 7-cyano-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole a) 7-cyanoimidazo [5, 1-b] thiazole To a suspension of 997 milligrams of 7-carbamoylimidazo [5, 1-b] thiazole in 80 milliliters of dichloromethane were added under cooling with ice, 7.28 milliliters of N, N-diisopropylethylamine and 2.23 milliliters of phosphorus oxychloride. After the reaction mixture was stirred at the same temperature, it was drained in ice water, the pH was adjusted to 7.5 with aqueous sodium hydrogen carbonate, and extracted three times with dichloromethane. The organic layer was dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained in this way was purified by column chromatography on silica gel (dichloromethane: methanol = 15: 1). to provide 871 milligrams of 7-cyanoimidazo [5, 1-b] thiazole. Nuclear Magnetic Resonance (CDCI3) d: 7.08 (HH, d, J = 4.2 Hz), 7.56 (HH, d, J = 4.2 Hz), 8.01 (HH, s). b) 7-cyano-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole A solution of 903 milligrams of 7-cyanoimidazo [5, 1-b] thiazole in 35 milliliters of THF was cooled to - 78 ° C. under an argon atmosphere, and 6.36 milliliters of a 1.0 N solution of lithium bistrimethylsilylamide in THF were added dropwise, at an internal temperature of -70 ° C - -65 ° C. After the reaction mixture was stirred at the same temperature for 1 hour, 1.81 milliliters of tri-n-butylstannyl chloride was added, and the mixture was stirred at the same temperature. for 1 hour. The reaction mixture was diluted with 100 milliliters of a semi-saturated aqueous ammonium chloride solution and extracted with 100 milliliters of ethyl acetate. The organic layer was dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained in this way was purified by column chromatography on silica gel (hexane: ethyl acetate and 3: 1) to give the heading compound in a yield of 795 milligrams. Nuclear magnetic resonance (CDCI3) d: 0.92 (9H, t, J = 7.3 Hz), 1.19 (6H, m), 1.36 (6H, m), 1.58 (6H, m), 7.26 (IH, s), 7.93 ( ÍH, s).

Preparation 12 7-Ethyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole and 7-ethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole a) 7 -vinylimidazo [5, 1-b] thiazole To a solution of 5.0 grams of 7-iodoimidazo [5, 1-b] thiazole in 40 milliliters of NMP was added under the argon atmosphere, 550 milligrams of tris (dibenzylideneacetone) dipalladium, 558 milligrams of tri-2-furyl phosphine and 6.42 milliliters of tri-n-butylvinyltin, and the mixture was reacted at 70 ° C for 1.5 hours and at 80 ° C for 2 hours. The reaction mixture was emptied into a mixture of 50 milliliters of a - aqueous saturated sodium hydrogen carbonate solution and 50 milliliters of a saturated saline solution and extracted twice with 200 milliliters of ethyl acetate. The combined organic layers washed three times with 200 milliliters of saline solution dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained in this way was purified by silica gel column chromatography (dichloromethane: ethyl acetate = 15: 1) to provide 7-vinylimidazo [5, 1-b] thiazole in an amount of 1.99 grams. Nuclear magnetic resonance (CDCI3) d: 5.27 (ΔH, d), 5.41 (ÍH, d), 6.80 (ÍH, dd), 6.91 (ÍH, d), 7.42 (1, d), 7.98 (ÍH, S). b) 7-ethylimidazo [5, 1-b] thiazole To a solution of 5.0 grams of 7-vinylimidazo [5, 1-b] thiazole in 40 milliliters of ethanol and 8 milliliters of water added 2.0 grams of 10 percent of Pd-C, and the mixture was stirred under the atmosphere of hydrogen at room temperature overnight. The catalyst was removed by filtration, and the filtrate was concentrated to a small volume. The concentrated material was diluted with 10 milliliters of a saturated aqueous sodium hydrogen carbonate solution and extracted with 100 milliliters of ethyl acetate. The organic layer was washed with an aqueous saline solution and dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained in this way was purified by column chromatography on silica gel (dichloromethane: ethyl acetate = 3: 2) to provide 1.27 grams of 7-ethylimidazo [5, 1-b] thiazole. Nuclear magnetic resonance (CDC13) d: 1.33 (3H, t), 2.76 (2H, c), 6.76 (H, d), 7.32 (H, d), 7.91 (H, s). c) 7-ethyl-3-tri-n-butylstannyl) imidazo [5, 1-b] thiazole and 7-ethyl-2-tri-n-butylstannyl) imidazo [5, 1-b] thiazole In the same way as in Preparation 3, 1.50 grams of 7-ethyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole eat a low polar component from 1.27 grams of 7-ethylimidazo [5, 1-b ] thiazole Nuclear magnetic resonance (CDCI3) d: 0.90 (9H, t), 1.1-1.5 (15H, m), 1.5-1.7 (6H, m), 2.76 (2H, c) 6.57 (H, s), 7.82 (H, s). In addition, 1.32 grams of 7-ethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole was obtained as a high polar component. Nuclear Magnetic Resonance (CDCI3) d: 0.92 (9H, t), 1.1-1.5 (15H, m), 1.5-1.7 (6H, m), 2.75 (2H, c), 7.09 (H, s), 7.86 (H) , s).

Preparation 13 7- (1-t-Butyldimethylsilyloxy) ethyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole and 7- (1-t-butyldimethylsilyloxy) ethyl-2- (tri-n- butylstanyl) imidazo [5, 1-b] thiazole a) 1 ~ (1-hydroxy) ethylimidazo [5, 1-b] thiazole A solution of 3.043 grams of 7-formyl [5, 1-b] thiazole in 60 milliliters of Dry THF was cooled to -58 ° C under the argon atmosphere. To this solution added 23 milliliters of a 0.92 M methylmagnesium bromide solution in THF under stirring at -60 ° C to -55 ° C over 10 minutes, the mixture was further stirred at room temperature during 10 minutes, and then directly heated directly to room temperature with stirring for 2 additional days. The reaction mixture was diluted with 50 milliliters of a saturated aqueous ammonium chloride solution, salted and extracted four times with 150 milliliters of ethyl acetate.The combined organic layer was dried through sodium sulfate. Anhydrous, filtered and the solvent was removed under reduced pressure The yellow oil obtained in this way was purified by silica gel column chromatography (dichloromethane: methanol = 95: 5) to provide 7- (l-hydroxy) ethylimidazo [5, 1-b] thiazole as light yellow crystals in a 2.164 gram run.

- - Nuclear magnetic resonance (CDCI3) d: 1.62 (3H, d, J = 6.5 Hz), 2.95 (HH, broad), 5.08 (1H, c, J = 6.5 Hz), 6.82 (HH, d; J = 4.3 Hz ), 7.37 (HH, d, J = 4.3 Hz), 7.94 (HH, s). MS (STSP): 169 (M + + H). b) 7. (1-t-Butyldimethyloxy) ethylimidazo [5, 1-b] thiazole To a solution of 2.086 grams of 7- (l-hydroxy) ethylimidazo [5, 1-b] thiazole in 12.4 milliliters of dry DMF was they added under ice-cooling 1098 grams of imidazole and 2150 grams of t-butyldimethylsilyl chloride, and the mixture was immediately stirred under the argon atmosphere for 1 hour. The reaction mixture was diluted with 100 milliliters of ethyl acetate and washed three times with 50 milliliters of a semi-saturated aqueous saline solution. The organic layer was dried through anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure. The yellow oil obtained in this way was purified by column chromatography on silica gel (dichloromethane only dichloromethane: methanol = 96: 4) to provide 3440 grams of 7- (1-t-butyldimethyloxy) ethylimidazo [5, 1-b ] thiazole as milk-white crystals in a yield of 3440 grams Nuclear Magnetic Resonance (CDCI3) d: 0.09 (3H, s), 0.12 (3H, s), 0.95 (9H, s), 1.52 (3H, d, J = 6.3 Hz), 5.10 (ÍH, - - c, J = 6.3 Hz), 6.77 (1H, d, J = 4.3 Hz), 7.33 (1H, d, J = 4.3 Hz), 7.90 (1H, s). MS (TSP): 283 (M + + H). c) 7- (1-t-butyldimethylsilyloxy) ethyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole y and 7- (l-butyldimethylsilyloxy) ethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole In the same manner as in Preparation 3, 7- (1-t-butyldimethylsilyloxy) ethyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole was obtained as a low polar component in a yield of 1.38 grams of 1.67 grams of 7- (1-t-butyldimethylsilyloxy) ethylimidazo [5, 1-b] thiazole. Nuclear Magnetic Resonance (CDCI3) d: 0.08 (3H, s), 0.12 (3H, s), 0.89 (9H, t, J = 7.3 Hz), 0.95 (9H, s), 1.20 (6H, m), 1.34 (6H, m), 1.54 (9H, m), 5.10 (ÍH, c, J = 6.3 Hz), 6.59 (1H, s), 7.82 (1, s). In addition, 7 (1-t-butyldimethylsilyloxy) ethyl-2- (tri-n-butyl-stanyl) imidazo was obtained [5, 1-b] thiazole as a high polar component in a yield of 812 milligrams. Nuclear Magnetic Resonance (CDCI3) d: 0.09 (3H, s), 0.12 (3H, s), 0.91 (9H, t, J = 7.4 Hz), 0.95 (9H, s), 1.13 (6H, m), 1.34 (6H, m), 1.55 (9H, m), 5.08 (ÍH, c, J = 6.3 Hz), 7.09 (1H, s), 7.85 (1H, s).

Preparation 14 7-cyano-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole, 7-methoxyiminomethyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole (geometric isomer derived from a raw material that is a high polar oxime isomer, 7-cyano-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole, and 7-methoxy-iminomethyl-2- (tri-n) -butylstannyl) imidazo [5, 1-b] thiazole (geometric isomer derived from a raw material which is a high polar oxime isomer a) 5-formylimidazo [5, 1-b] thiazole and 7-formylimidazo [5, 1 -b] thiazole To the mixture of 15.48 milliliters of DMF and 80 milliliters of dichloromethane was added dropwise a solution of 18.32 milliliters of phosphorus oxychloride with 80 milliliters of dichloromethane, under cooling with ice.The mixture was reacted at room temperature during 30 minutes and a solution of imidazo [5, 1-b] thiazole in 40 milliliters of chloromethane was added dropwise After heating at reflux for 2.5 hours, the reaction mixture was emptied in wire, it was adjusted to a pH of 9.8 with a 5 N aqueous sodium hydroxide solution, extracted five times with 200 milliliters of dichloromethane, dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained in this way was purified by chromatography - - of column on silica gel (dichloromethane: ethyl acetate = 5: 1 - ethyl acetate alone - dichloromethane: methanol = 10: 1). As a low polar component, 5 for unlimited [5, 1-b] thiazole was obtained in a yield of 495 milligrams. Nuclear magnetic resonance (CDCI3) d: 7.18 (1H, d, J = 4.1 Hz), 7.46 (HH, s), 8.46 (HH, d, J = 4.1 Hz), 9.76 (HH, s). In addition, as a high polar component, 7-formylimidazo [5, 1-b] thiazole was obtained, in a yield of 2.37 grams. Nuclear magnetic resonance (CDCI3) d: 7.17 (ΔI, d, J = 4.1 Hz), 7.60 (ΔI, d, J = 4.1 Hz), 8.07 (ΔI, s), 9.93 (1H, s). b) 7-methoxyiminomethylimidazo [5, 1-b] thiazole (high polar geometric isomer) and 7-methoxyiminomethylimidazo [5, 1-b] thiazole (low polar geometric isomer) A suspension of 249 milligrams of 7-formylimidazo [5, 1 -b] thiazole in 10 milliliters of ethanol was added 219 milligrams of 0-methylhydroxylamine hydrochloride and 2.67 milliliters of an IN sodium hydroxide solution. The reaction mixture was stirred at room temperature for 20 hours, concentrated, then diluted with 50 milliliters of water, and extracted with dichloromethane. The organic layer was dried through - - anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained in this way was purified by silica gel column chromatography (dichloromethane: ethyl acetate = 1: 1) to give 7-methoxyiminomethylimidazo [5, 1-b] thiazole (low polar geometric isomer), in a yield of 164 milligrams of the low polarity fraction. Nuclear Magnetic Resonance (CDCI3) d: 3.96 (3H, s), 7.01 (1H, d, J = 4.1 Hz), 7.48 (IH, d, J = 4.1 Hz), 8.02 (IH, s), 8.24 (IH, s). In addition, 7-methoxyiminomethylimidazo [5, Ib] thiazole (high polar geometric isomer) was obtained in a yield of 71 milligrams of the low polar fraction. Nuclear Magnetic Resonance (CDCI3) d: 4.40 (3H, s), 6.90 (ΔH, d, J = 4.4 Hz), 7.43 (ΔI, d, J = 4.4 Hz), 7.46 (lH, s), 7.94 (ΔI, s). c) 7-cyano-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole, 7-methoxyiminomethyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole (geometric isomer) derived from raw material which is a high polar oxime isomer), 7-cyano-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole, and 7-methoxyiminomethyl-2- (tri-n-butylstannyl ) imidazo [5, 1-b] thiazole (geometric isomer derived from a raw material that is a high polar oxime isomer) _ - - In the same manner as in Preparation 3, 7-cyano-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole was obtained in an amount of 67 milligrams of the fraction having Rf = 0.8 (n-hexane: ethyl acetate = 3: 1) from 1.17 grams of 7-methoxyiminomethylimidazo [5, 1-b] thiazole (high polar geometric isomer). Nuclear magnetic resonance (CDCI3) d: 0.90 (9H, t, J = 7.2 Hz), 1.26 (6H, m), 1.35 (6H, m), 1.57 (6H, m), 6.80 (H, s), 7.87 ( ÍH, s). - In addition, 7-methoxyiminomethyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole (geometric isomer derived from a raw material which is a high polar oxime isomer) obtained in a yield of 1.26 was obtained grams of the fraction having Rf = 0.6 (n-hexane: ethyl acetate = 3: 1). Nuclear magnetic resonance (CDCI3) d: 0.90 (9H, t, J = 7.4 Hz), 1.22 (6H, m), 1.34 (6H, m), 1.56 (6H, m), 3.98 (3H, s), 6.71 ( 1H, s), 7.46 (H, s), 7.84 (H, s). In addition, 7-cyano-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole was obtained in a yield of 150 milligrams of the fraction having Rf = 0.4 (n-hexane: ethyl acetate = 3 : 1) . The nuclear magnetic resonance data of this compound all were in agreement with those obtained in Preparation 11.

- In addition, 7-methoxyiminomethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole (geometric isomer derived from a raw material which is a high polar oxime isomer) obtained in a yield of 980 milligrams was obtained of the fraction having Rf = 0.2 (n-hexane: ethyl acetate = 3: 1). Nuclear Magnetic Resonance (CDCI3) d: 0.92 (9H, t, J = 7.3 Hz), 1.16 (6H, m), 1.36 (6H, m), 1.58 (6H, m), 4.00 (3H, s), 7.18 (1H, s), 7.45 (ÍH, s), 7.89 (ÍH, s).

Preparation 15 7-cyano-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole, 7-methoxyimino-methyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole ( stereoisomer derived from a raw material that is a low polar oxime isomer), 7-cyano-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole, and 7-methoxyiminomethyl-2- (tri-n -butylstanil) imidazo [5, 1-b] thiazole (stereoisomer derived from a raw material which is a low polar oxime isomer) In the same manner as in Preparation 3, 7-cyano-3- (tri-n) was obtained -butylstanil) imidazo [5, 1-b] thiazole in a yield of 288 milligrams of the fraction having Rf = 0.8 (n-hexane: ethyl acetate = 3: 1) from 1.47 grams of 7-methoxyiminomethylimidazo [5 , 1 B] - - thiazole (low polar geometric isomer) described in Preparation 14-b). The nuclear magnetic resonance data of this compound were all in agreement with those obtained in Preparation 14. In addition, 7-methoxyiminomethyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole (geometric isomer) was obtained derived from a raw material which is a low polar oxime isomer) in a yield of 1.68 grams of the fraction having Rf = 0.7 (n-hexane: ethyl acetate = 3: 1).

Nuclear Magnetic Resonance (CDCI3) d: 0.90 (9H, t, J = 7.4 Hz), 1.24 (6H, m), 1.35 (6H, m), 1.55 (6H, m), 3.96 (3H, s), 6.81 ( ÍH, s), 7.92 (ÍH, s), 8.25 (ÍH, s). In addition, 7-cyano-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole was obtained in a yield of 353 milligrams of the fraction having Rf = 0.4 (n-hexane: ethyl acetate = 3 : 1) . The nuclear magnetic resonance data of this compound were all in agreement with those obtained in Preparation 11. In addition, 7-methoxyiminomethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole (isomer) was obtained geometric derivative of a raw material that is a low polar oxime isomer) obtained in a yield of 704 milligrams of - - the fraction having Rf = 0.3 (n-hexane: ethyl acetate = 3: 1). Nuclear magnetic resonance (CDCI3) d: 0.92 (9H, t, J = 7.3 Hz), 1.18 (6H, m), 1.35 (6H, m), 1.57 (6H, m), 3.97 (3H, s), 7.22 ( ÍH, s), 7.96 (ÍH, s), 8.23 (ÍH, s).

Preparation 16 7-formylaminomethyl-3-tri-n-butylstannyl) imidazo [5, 1-b] thiazole and 7-formylaminomethyl-2- (tri-n-butylstannyl] imidazo [5, 1-b] thiazole Using 0.72 gram of 7-formylaminomethylimidazo [5, 1-b] thiazole, 7-formylaminomethy1-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole was obtained in a yield of 0.99 gram as a low polar component, and -formylaminomethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole, in a yield of 0.64 gram as the high polar component in the same manner as in Preparation 1. 7-formylaminomethyl-3-) tri-n-butylstannyl) imidazo [5, 1-b] thiazole Nuclear magnetic resonance (CDCI3) d: 0.90 (9H, t, J = 7.1 Hz), 1.22 (6H,), 1.34 (6H, m), 1.55 ( 6H, m), 4.58 (2H, d, J = 5.6 Hz), 6.32 (IH, broad), 6.63 (IH, s), 7.85 IH, s), 8.27 (IH, s). - - 7-formylaminomethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole Nuclear magnetic resonance (CDCI3) d: 0.92 (9H, t, J = 7.3 Hz), 1.16 (6H, m), 1.35 (6H, m), 1.58 (6H, m), 4.56 (2H, d, J = 6.4 Hz), 6.51 (HH, broad s), 7.13 (1H, s), 7.89 (HH, s), 8.38 (HH) , s).

Preparation 17 7- (t-butyldimethylsilyloxy) methyl-3- (tri-n-butylstannyl) imidazole [5, 1-b] thiazole and 7- (t-butyldimethylsilyloxy) methyl-2- (tri-n-butyl-stanyl) imidazo [5, 1-b] thiazole a) 7- (t-butyldimethylsilyloxy) methylimidazo [5, 1-b] thiazole To a solution of 2.42 milligrams of 7-hydroxymethylimidazo [5, 1-b] thiazole in 15 milliliters of DMF were added under ice-cooling, 1.4 grams of imidazole and 2.73 grams of t-butyldimethylsilyl chloride, and the mixture was stirred at the same temperature for 2 hours. The DMF was removed under reduced pressure, and the residue was extracted twice with ethyl acetate. The organic layer was washed twice with a saturated aqueous sodium chloride solution, dried through anhydrous magnesium sulfate and stirred under reduced pressure to provide 7- (t-butyldimethylsilyloxy) methylimidazo [5, 1-b] thiazole. , in a yield of 4.02 grams.

- Nuclear magnetic resonance (CDCI3) d: 0.13 (6H, s), 0.97 (9H, s), 4.88 (2H, s), 6.78 (IH, d, J = 4.1 Hz), 7.34 (IH, d, J = 4.1 Hz), 7.92 (1H, s). b) 7- (t-butyldimethylsilyloxy) methyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole and 7- (t-butyldimethylsilyloxy) ethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole A solution of 2.25 grams of 7- (t-butyldimethylsilyloxy) methylimidazo [5, 1-b] thiazole in 5 milliliters of THF was cooled to -78 ° C under the atmosphere of argon, and 5.3 milliliters of a 1.6 N solution of n-butyl lithium in n-hexane was added dropwise at the same temperature. After the reaction mixture was stirred for 2 hours, 2.24 milliliters of tri-n-butyl-stanyl chloride was added and the resulting mixture was stirred at the same temperature for 1 hour, and for 3 hours through which the temperature rose to 0 ° C. The reaction mixture was diluted with a saturated sodium chloride solution and extracted twice with ethyl acetate. The organic layer was dried through anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue obtained in this way was purified by chromatography on silica gel (hexane: ethyl acetate = 2: 1). - 7- (t-butyldimethylsilyloxy) methyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole was obtained in a yield of 1.54 grams of the fraction having Rf = 0.6 (hexane: ethyl acetate = eleven) . Nuclear Magnetic Resonance (CDCI3) d: 0.01 (6H, s), 0.76 (9H, t, J = 7.1 Hz), 0.83 (9H, s), 1.04 - 1.26 (12H, m), 1.38 - 1.49 (6H, m ), 4.74 (2H, s), 6.47 (1H, s), 7.71 (ÍH, s). MS (STP): 559 (M + + 3 H), 557 M + + H). In addition, 7- (t-butyldimethylsilyloxy (methyl-2- (tri-n-butyl-stanyl) imidazo [5, 1-b] thiazole was obtained in a yield of 1.67 grams of the fraction having Rf = 0.3. (CDCI3) d: 0.01 (6H, s), 0.78 (9H, t, J = 7.1 Hz), 0.83 (9H, s), 1.00 - 1.07 (6H, m), 1.18 - 1.30 (6H, m), 1.40 - 1.50 (6H, m), 4.73 (2H, s), 6.97 (1H, s), 7.73 (1H, s) MS (TSP): 559 (M + + 3H), 557 (M + + H).

Preparation 18 7- (N-methylcarbamoyl) -3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole and 7- (N-methylcarbamoyl) -2- (tri-n-butylstannyl] imidazo [5, 1-b] thiazole a) 7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazole - To a solution of 2.06 grams of 7-carboxylimidazo [5, 1-b] thiazole in 90 milliliters of DMF were added 4.98 grams of 1-hydroxybenzotriazole and 4.72 grams of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, and The mixture was stirred at room temperature for 10 minutes. Then, 18.5 milliliters of a 2N solution of methylamine in THF was added and the mixture was stirred at the same temperature at 18 hours. The reaction mixture was diluted with water and adjusted to a pH = 9.6 with pulverized potassium carbonate and extracted five times with dichloromethane and five times with ethyl acetate. The combined organic layer was dried through anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue obtained in this way was purified by silica gel column chromatography (dichloromethane: methanol = 10: 1) followed by Sephadex LH-20 (dichloromethane: methanol = 1: 1) to give 0.80 gram of 7- (N-) methylcarbamoyl) imidazo [5, 1-b] thiazole. Nuclear Magnetic Resonance (CDCI3) d: 3.01 (3H, d, J = 5.0 Hz), 6.90 (IH, broad), 7.00 (IH, d, J = 4.1 Hz), 7.48 (IH, d, J = 4.1 Hz ), 7.92 (1H, s). MS (El): 181 (M +). b) 7- (N-methylcarbamoyl) -3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole 7- (N-methylcarbamoyl) -2- (tri-n-butylstannyl) imidazo [5, 1 -b] thiazole A solution of 716 milligrams of 7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazole in 35 milliliters of THF was cooled to -78 ° C under the argon atmosphere, and 6.0 drops were added. milliliters of a 1.6 N solution of n-butyl lithium in n-hexane at the same temperature. After the reaction mixture was stirred for 1.5 hours, 1.40 milliliters of tri-n-butylstannyl chloride was added, and the mixture was stirred for 5 hours through which the temperature was raised to -40 ° C. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried through anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue obtained in this way was purified by column chromatography on silica gel (hexane: ethyl acetate = 3: 1). 7- (N-methylcarbamoyl) -3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole was obtained in a yield of 441 milligrams of the fraction having Rf = 0.5 (hexane: ethyl acetate = 1 : 1) . Nuclear magnetic resonance (CDCI3) d: 0.83 (9H, t, J = 7.3 Hz), 1.16 - 1.32 (12H, m), 1.44 - 1.61 (6H, m), 2.94 (3H, d, J = 5.0), 6.72 (ÍH, s), 6.70 -6.80 (ÍH, 'm), 7.73 (ÍH, s).

In addition, 702 milligrams of 7- (N-methylcarbamoyl) -2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole were obtained from the fraction having Rf = 0.4. Nuclear magnetic resonance (CDC13) d: 0.91 (9H, t, J = 7.3 Hz), 1.15 - 1.40 (12H, m), 1.55 - 1.60 (6H, m), 3.00 (3H, d, J = 5.2 Hz), 6.80 - 6.88 (1H, m), 7.21 (H, s), 7.85 (H, s). MS (APCI): 472 (M + + 3 H), 470 (M + + H).

Preparation 19 7-methyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole and 7-methyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole A solution of 1.66 N of n-butyl lithium / n-hexane (15.8 milliliters) dissolved in dry THF (75 milliliters) cooled to -69 ° C under the argon atmosphere, and a solution of 3,455 grams of 7-methylimidazo [5, 1 -b] thiazole in 50 milliliters of THF were added dropwise under stirring at -69 ° C to -66 ° C over 20 minutes. The reaction mixture was further stirred at the same temperature for 10 minutes, and 7.8 milliliters of tri-n-butylstannyl chloride were added dropwise at the same temperature over a period of 10 minutes. Then, the reaction mixture was gradually warmed to room temperature, and stirred for 15 hours. The reaction mixture was diluted with 100 milliliters of a semi-saturated aqueous saline solution, and - it was extracted with 250 milliliters of ethyl acetate. The organic layer was dried through anhydrous magnesium sulfate, filtered and the solvent was removed by distillation. The oil obtained in this way was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 2: 1-1: 1). 7-Methyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole was obtained as a yellow oil in a yield of 4,760 grams of the fraction having Rf = 0.5 (n-hexane: ethyl acetate = 2: 1). Nuclear Magnetic Resonance (CDCI3) d: 0.89 (9H, t, J = 7.2 Hz), 1.17 - 1.23 (6H, m), 1.27 -1.40 (6H, m), 1.50 -1.65 (6H, m), 2.36 (3H , s), 6.57 (1H, s), 7.83 (ÍH, s). MS (TS): 429 (M + + 3 H), 427 (M + + H). In addition, 7-methyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole was obtained as a yellow oil in a yield of 3.653 grams of the fraction having Rf = 0.2 (n-hexane: acetate ethyl = 2: 1). Nuclear Magnetic Resonance (CDCI3) d: 0.91 (9H, t, J = 7.2 Hz), 1.11 - 1.17 (6H, m), 1.19 -1.41 (6H, m), 1.53-1.63 (6H, m), 2.34 (3H , s), 7.08 (ÍH, s), 7.85 (1H, s). MS (TS): 429 (M + + 3 H), 427 (M + + H).

Preparation 20 5, 7-dimethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole - - a) 2- (1-acetylamino) ethylthiazole To a solution of 3.40 grams of 2- (l-amino) ethylthiazole in 53 milliliters of THF were added 2.6 milliliters of dry pyridine, and the mixture was cooled to -70 ° C under a argon atmosphere. To the mixture 2.6 milliliters of acetic anhydride was added dropwise over a period of 5 minutes, and further it was stirred in an ice bath for 1 day. The reaction mixture was diluted with 40 milliliters of 5 percent aqueous sodium hydrogen carbonate, and extracted once with 200 milliliters and three times with 100 milliliters of dichloromethane. The combined organic layer was dried through anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The solid residue obtained in this way was purified by column chromatography on silica gel (ethyl acetate alone - ethyl acetate: methanol: 96: 4) to give 2- (1-acetylamino) ethylthiazole as a milk-white powder in a yield of 3,456 grams. Nuclear Magnetic Resonance (CDCI3) d: 1.62 (3H, d, J = 6.9 Hz), 2.05 (3H, s), 5.44 (1H, quintet, J = 6.9 Hz) 6.43 (ÍH, broad), 7.28 (1H, d, J = 3.3 Hz), 7.71 (ÍH, d, J = 3.3 Hz). MS (TSP): 171 (M + + H). b) 5, 7-dimethylimidazo [5, 1-b] thiazole To 3.392 grams of 2- (1-acetylamino) ethylthiazole were added 17 milliliters of dry toluene and 9 milliliters of phosphorus oxychloride, and the mixture was stirred at a temperature of 90 ° C bath for 75 minutes. The reaction mixture was cooled to room temperature, diluted with 30 milliliters of distilled water and 100 milliliters of dichloromethane, neutralized under stirring with potassium carbonate, desalted, and the organic layer separated. The aqueous layer was further extracted with 50 milliliters of dichloromethane. The combined organic layer was dried through anhydrous potassium carbonate. The crude fine crystalline product thus obtained was purified by column chromatography on silica gel (dichloromethane: methanol = 98: 2) to provide, 7-dimethylimidazo [5, 1-b] thiazole as white crystals such as milk in a yield of 2787 grams. Nuclear magnetic resonance (CDCI3) d: 2.30 (3H, s), 2.53 (3H, s), 6.71 (IH, d, J = 4.2 Hz), 7.12 (1H, d, J = 4.2 Hz). MS (TSP): 153 (M + + H). c) 5, 7-dimethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole To 50 milliliters of anhydrous THF cooled to -65 ° C under an argon atmosphere was added 10.9 milliliters of a solution 1.63 N of n-butyl lithium / n-hexane, and the - - solution of 2,564 grams of 5,7-dimethylimidazo [5, 1-b] thiazole in 17 milliliters of anhydrous THF were further added dropwise at -64 ° C to -60 ° C over a period of 15 minutes. The reaction mixture was then stirred at the same temperature for 80 minutes. Then 5.0 milliliters of tri-n-butylstannyl chloride was added dropwise to the mixture at a temperature of -63 ° C to -58 ° C over a period of 10 minutes, heated to -30 ° C, and stirred additionally for 110 minutes. The reaction mixture was diluted with 100 milliliters of a semi-saturated aqueous saline solution, extracted with 150 milliliters of ethyl acetate. The organic layer was dried through anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure. The oil obtained in this way was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 1: 1-1: 2) to give the title compound as a light orange oil in a yield of 6.164 grams. Nuclear Magnetic Resonance (CDCI3) d: 0.92 (9H, t, J = 7.2 Hz), 1.10 - 1.17 (6H, m), 1.30 -142 (6H, m), 1.53-1.65 (6H, m), 2.29 (3H , s), 2.53 (3H, s), 6.85 (ÍH, s). MS (TSP): 443, 441, 439.

Preparation 21 - - 7-methoxymethyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole and 7-methoxymethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole a) 7-methoxymethylimidazo [5, 1-b] thiazole To a solution of 2.0 grams of 7-hydroxymethylimidazo [5, 1-b] thiazole in 25 milliliters of DMF were added under ice-cooling, 600 milligrams of sodium hydride (60 percent in oil ) under an argon atmosphere. White insoluble materials were produced in a short time. When agitation becomes difficult, DMF is added. After 30 minutes, 2.0 grams of iodomethane was added to dissolve the precipitated material. After further stirring for 1 hour, 200 milliliters of ethyl acetate and 100 milliliters of a semi-saturated aqueous saline solution were added and the mixture was stirred and separated. The organic layer was washed three times with 100 milliliters of semi-saturated aqueous saline solution, dried through anhydrous magnesium sulfate and purified by silica gel column chromatography and on Sephadex LH-20 to provide 1.41 grams of silica gel. -methoxymethylimidazo [5, 1-b] thiazole. Nuclear magnetic resonance (CDCI3) d: 3.43 (3H, s), 4.59 (2H, s), 6.83 (H, d, J = 4.2 Hz), 7.38 (1H, d, J = 4.2 Hz), 7.96 (H, s). - - b) 7-methoxymethyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazolothiazole and 7-methoxymethyl-2- (tri-n-butylstannyl] imidazo [5, 1-b] thiazole A solution of 925 milligrams of 7-methoxymethylimidazo [5, 1-b] thiazole in anhydrous THF was cooled to -70 ° C under an argon atmosphere and 3.54 milliliters of a 1.6 N solution of n-butyllithium / n- was slowly added. hexane and the mixture was stirred for 1 hour.A solution of 1.88 grams of tri-n-butylstannyl chloride in 2 milliliters of anhydrous THF was slowly added to the reaction mixture, and the mixture was stirred for an additional 1.5 hours. addition of 100 milliliters of ethyl acetate, the solvent was removed by distillation to concentrate the mixture to a total volume of about 1 milliliter Purification by silica gel chromatography provided 896 milligrams of 7-methoxymethyl-3- (tri-). n-butylstannyl) imidazo [5, 1-b] thiazole from a low polar fraction eluted as dichloro methane: ethyl acetate = 4: 1. Nuclear magnetic resonance (CDCI3) d: 0.80 - 1.80 (27H, m), 3.42 (3H, s), 4.58 (2H, s), 6.63 (HH, s), 7.87 ( ÍH, s). In addition, purification by column chromatography on silica gel provided 712 milligrams of 7-methoxymethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole of - - a high polar fraction eluted with dichloromethane: ethyl acetate 1: 1 - 1: 4. Nuclear magnetic resonance (CDCI3) d: 0.80-1.80 (27H, m), 3.42 (3H, s), 4.57 (2H, s), 7.13 (ÍH, s), 7.90 (ÍH, s).

Preparation 22 7- (N, N-dimethylcarbamoyl) -3- (tri-n-butylstannyl) imidazothiazole and 7- (N, N-dimethylcarbamoyl) -2- (tri-n-butylstannyl) imidazothiazole (approximately a mixture of 1: 1) a) 7- (N, N-dimethylcarbamoyl) imidazo [5, 1-b] thiazole To a solution of 1.71 grams of 7-carboxylimidazo [5, 1-b] thiazole in 34 milliliters of DMF was added 5.45 grams of 1-hydroxybenzotriazole and 6.80 grams of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride at room temperature under the argon atmosphere, and the mixture was stirred for 1 hour. To the reaction mixture were added under ice-cooling 20 milliliters of a solution of dimethylamine saturated in THF, and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with 300 milliliters of dichloromethane and 180 milliliters of water, stirred vigorously and separated. The organic layer was dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained from this - This was purified by silica gel column chromatography (dichloromethane: methanol = 94: 6-90: 10) to provide 663 milligrams of 7- (N, N-dimethylcarbamoyl) imidazo [5, 1-b] thiazole. Nuclear Magnetic Resonance (CDCI3) d: 3.0 - 3.8 (6H, m), 6.99) ΔH, d, J = 4.2 Hz), 7.47 (ΔH, d, J = 4.2 Hz), 7.93 (ΔH, s). b) 7- (N, N-dimethylcarbamoyl) -3- (tri-n-butylstannyl) imidazothiazole and 7- (N, N-dimethylcarbamoyl) -2- (tri-n-butyl-stanyl) imidazothiazole (mixture) A solution of 660 milligrams of 7- (N, N-dimethylcarbamoyl) imidazo [5, 1-b] thiazole in 30 milliliters of anhydrous THF was cooled to -55 ° C under an argon atmosphere. 2.4 milliliters of a 1.6 N solution of n-butyllithium / n-hexane was added slowly and the mixture was stirred for 1 hour. A solution of 1.30 grams of tri-n-butylstannyl chloride in 10 milliliters of anhydrous THF was added slowly and the reaction mixture was stirred for 1 hour. The reaction mixture was diluted with 120 milliliters of ethyl acetate and 30 milliliters of water, stirred and separated. The organic layer was dried through anhydrous magnesium sulfate and the solvent was removed to concentrate the organic layer to a total volume of about 1 milliliter. The residue obtained in this way was purified by chromatography on silica gel (hexane: acetate - - ethyl = 1: 1) to provide 980 milligrams of the header compound as a mixture of about 1: 1. Nuclear Magnetic Resonance (CDCI3) d: 0.7-1.7 (27H, m), 2.9-3.9 (6H, broad s) , 6.81 (0.5H, s, derivative of 3-stanyl), 7.21 (0.5H, s, 2-stanyl derivative), 7.84 (0.5 H, s, 3-stanyl derivative), 7.88 (0.5H, s, 2-stanyl derivative.

Example 1 Acid (SS, 5R, 6S) -6- ((IR-1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-1-carbapen-2-em- 3-carboxylic a) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen -2-em-3-carboxylate of 4-nitrobenzyl To a solution of 7.24 grams of (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2-oxo-l 4-nitrobenzylcarbapenam-3-carboxylate in 150 milliliters of dry acetonitrile, 6.97 milliliters of N, N-diisopropylethylamine were added dropwise, followed by 3.70 milliliters of anhydrous trifluoromethanesulfonic acid under an argon atmosphere at -15 ° C. . After the reaction mixture was stirred at the same temperature for 30 minutes, it was diluted with 500 milliliters of ethyl acetate, and washed sequentially in a semi-saturated aqueous saline solution, a mixture of the semi-aqueous aqueous saline solution. saturated and IN hydrochloric acid (pH 1.1), a mixture of the semi-saturated aqueous saline solution and saturated aqueous sodium hydrogen carbonate (pH of 8.9), and the saturated aqueous saline solution. After drying through anhydrous magnesium sulfate, the reaction mixture was filtered, diluted with 40 milliliters of dry N-methylpyrrolidine, and the ethyl acetate and acetonitrile were removed under reduced pressure. The residue was mixed with a solution of 553 milligrams of tris (dibenzylidene ketone) dipalladium (O), 558 milligrams of tri-2-furylphosphine, 9.14 grams of 2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole in 10 milliliters of dry methylpyrrolidinone, and 5.47 grams of zinc chloride, and the mixture is stirred under the argon atmosphere at 50 ° C for 1 hour. The solvent was evaporated under reduced pressure, the concentrated material was diluted with 150 milliliters of diethyl ether and the supernatant liquid was separated. The procedure was repeated twice more, and the residue obtained in this manner was diluted with 400 milliliters of ethyl acetate and 80 milliliters of water. The insoluble materials were collected by filtration, and washed with ethyl acetate and water (insolubles 1). The organic layer was separated from the filtrate, dried through anhydrous magnesium sulfate and the solvent was dried. removed under reduced pressure. The residue was diluted with 100 milliliters of diethyl ether and 100 milliliters of ethyl acetate, and the insoluble materials were collected by filtration (insoluble 2). The insoluble materials 1 described above were diluted with 1000 milliliters of ethyl acetate, 500 milliliters of methanol, and 500 milliliters of acetone, and the mixture was stirred for 45 minutes at room temperature. After the insoluble materials were collected by filtration and the solvent was removed under reduced pressure, the residue was diluted with 30 milliliters of diethyl ether and 15 milliliters of ethyl acetate, and the insoluble materials were collected by filtration (insoluble 3) . Insoluble materials 2 and insoluble materials 3 were combined, dissolved in 100 milliliters of acetone, diluted with 900 milliliters of ethyl acetate and 400 milliliters of semi-saturated aqueous sodium hydrogen carbonate, and the mixture was stirred at room temperature. environment for 30 minutes. The insoluble materials were removed by filtration, and the organic layer was separated from the filtrate, washed three times with 500 milliliters of the semi-saturated aqueous saline solution, dried through anhydrous magnesium sulfate, and evaporated under reduced pressure. to provide 5.71 grams of (ÍS, 5R, 6S) -6- ((IR) -l-hydroxyethyl-2- (imidazo [5, 1-b] thiazole- - - 2-thiazol-yl) -l-methyl-l-carbapen-2-em-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (CDCI3) d: 1.31 (3H, d, J = 7. 4 Hz), 1.40 (3H, d, J = 6.3 Hz), 3.37 (1H, dd, J 1 = 6.6 Hz, J 2 = 2-8 Hz) '3-47 (1H > m)' 4-34 (1H m) 1 4-38 (1H 'dd, J 1 = 9.4 Hz, J 2 = 2-8 Hz), 5.28 (HH, d, J = 13.7 Hz), 5.53 (HH, d, J = 13.7 Hz ), 7.08 (ÍH, s), 7.68 (2H, d, J = 8. 5 Hz), 8.03 (HH, s), 8.24 (2H, d, J = 8.5 Hz), 8.34 (HH, s). b) Acid (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2 -em-3-carboxylic acid To a solution of 4.70 grams of (ÍS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) 4-Nitro-benzyl-1-methyl-l-carbapen-2-em-3-carboxylate in 90 milliliters of THF and 50 milliliters of a 1/15 M phosphate stabilizer (pH of 6.8) were added 7.0 grams of Pd-C at 10 percent. The reactor was purged with hydrogen, and the reaction mixture was stirred at room temperature for 4 hours. The catalyst was removed by filtration with Celite, and washed with 300 milliliters of water and 50 milliliters of THF. The filtrate was diluted with 200 milliliters of ethyl acetate and washed with water. The layer was separated from the filtrate and concentrated under reduced pressure to a volume of about - - 300 milliliters, which was purified by column chromatography on DIAION HP-20. The fraction containing the desired product was concentrated under reduced pressure, crystallized from 12 milliliters of water to provide 656 milligrams of the header compound. Nuclear Magnetic Resonance (DMSO-dg) d: 1.18 (3H, d, J = 6.1 Hz), 1.19 (3H, d, J = 7.1 Hz), 3.32 (ΔI, dd, J = 6.3 Hz, J2 = 2.8 Hz) , 3.60 (ÍH, m), 4.00 (ÍH, m), 4.25 (ÍH, dd, Jl = 9.6 Hz, J2 = 2.8 Hz), 5.10 (ÍH, broad), 7.02 (ÍH, s), 8.22 (ÍH, s), 8.37 (1H, s). MS (TS): 334 (M + + H).

Example 2 Acid (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em -3-carboxylic acid a) (SS, 5R, 6S) -6- [(IR) -1- (t-butyldimethylsilyloxy) ethyl] -2- (imidazo [5, 1-b] thiazol-2-yl) -l -methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl A solution of 292 milligrams of (IR, 3R, 5R, 6S) - 6- [(IR) -1- (t-butyldimethyl-silyloxy) ethyl] -l-methyl-2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl in 8 milliliters of dry acetonitrile was cooled on ice under an argon atmosphere and 0.267 milliliter of N, N-diisopropylethylamine was added per drop. , followed by 0.103 milliliter_ of acid - anhydrous trifluoromethanesulfonic acid. After the reaction mixture was stirred at the same temperature for 30 minutes, was diluted with ethyl acetate, a mixture of aqueous sodium hydrogen carbonate saturated with semi-saturated aqueous saline solution (pH of 8.9), and a semi-saturated aqueous saline solution in this sequence. The organic layer was dried through anhydrous magnesium sulfate, filtered, and mixed with 3 milliliters of N-methylpyrrolidinone, and the ethyl acetate was removed under reduced pressure. The residue was mixed with 17 milligrams of tris (dibenzylideneacetone) dipalladium (O), 17 milligrams of tri-2-furylphosphine, 376 milligrams of 2- ((tri-n-butylstannyl) imidazo [5, 1-b] thiazole in 1 milliliter of dry N-methylpyrrolidinone and 167 milligrams of zinc chloride, and the mixture was stirred under the argon atmosphere at 50 ° C for 4 hours.The reaction mixture was diluted with ethyl acetate, and washed with a saline solution. The aqueous layer was dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure.The residue obtained in this way was purified by column chromatography on silica gel (ethyl acetate) and on Sephadex. LH-20 (chloroform: methanol = 1: 1) in this sequence to provide 111 milligrams of (SS, 5R, 6S) -6- [(IR) -1- (t-butyldimethylsilyloxy) ethyl] -2- - - (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (CDCI3) d: 0.08 (3H, s), 0.10 (3H, s), 0.86 (9H, s), 1.26 (3H, d, J = 6.3 Hz), 1.28 (3H, d, J = 7.7 Hz), 3.33 (ÍH, dd, J1 = 4.7 Hz, J2 = 2.8 Hz), 3.41 (1H,), 4.31 (ÍH,), 4.37 (1H, dd, Jl = 9.6 Hz, J2 = 2.8 Hz), 5.26 (HH, d, J = 13.7 Hz), 5.49 (HH, d, J = 13.7 Hz), 7.26 (HH, s), 7.67 (2H, d, J = 8.3 Hz), 8.03 (HH, s), 8.23 (2H, d, J = 8.3 Hz), 8.33 (ÍH, s). b) (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2- 4-Nitrobenzyl em-3-carboxylate To a solution of 111 milligrams of (SS, 5R, 6S) -6- [(IR) -1- (t-butyldimethylsilyloxy) ethyl] -2- (imidazo [5, 1-] b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 3 milliliters of anhydrous THF were added 0.164 milliliter of acetic acid and 0.954 milliliter of a solution of 1M of tetra-n-butylammonium fluoride / THF, and the mixture was stirred at room temperature under an argon atmosphere for 20 hours. The reaction mixture was diluted with ethyl acetate, and washed with a mixed solvent of the semi-saturated aqueous saline solution and the saturated aqueous sodium hydrogen carbonate (pH 8.0), and the semi-saturated aqueous saline solution in this sequence. The organic layer was dried through sodium sulfate.

Anhydrous magnesium was filtered and the solvent was removed by distillation. The residue obtained in this way was purified by column chromatography on Sephadex LH-20 (chloroform: methanol = 1: 1) to provide 57.3 milligrams of (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (i-azozo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. The nuclear magnetic resonance data were in agreement with those in Example 1-a). c) Acid (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2 -em-3-carboxylic acid In the same manner as in Example 1-b), the (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-]) acid b] thiazol-2-yl) -lm.ethyl-l-carbapen-2-em-3-carboxylic acid was obtained from (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- ( Imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. The nuclear magnetic resonance data were in agreement with those in Example 1-a).

Example 3 - (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em- Pivaloyloxymethyl 3-carboxylate To a suspension of 947 milligrams of acid (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3-carboxylic acid in 180 milliliters of water was added 7.8 milliliters of 0.1 N aqueous sodium hydrogen carbonate, and the mixture was stirred at room temperature for 2 hours to form a solution, which then froze. The frozen solution was dissolved in 12 milliliters of dry DMF, mixed with 0.36 milliliter of iodomethyl pivalate under an argon atmosphere at -30 ° C and stirred for 1.5 hours during which the temperature was raised to -10 ° C. The reaction mixture was diluted with 100 milliliters of ethyl acetate, and washed with 100 milliliters of the semi-saturated aqueous saline solution. The organic layer was dried through anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to a total volume of 5 milliliters. The residue obtained in this way was purified by column chromatography on silica gel (chloroform: methanol = 10: 1) and on Sephadex LH-20 (chloroform: methanol = 1: 1) in this sequence to provide 576 milligrams of the header.

- - Nuclear magnetic resonance (CDCI3) d: 1.20 (9H, s), 1.29 (3H, d, J = 7.2 Hz), 1.36 (3H, d, J = 6.2 Hz), 3.33 (1H, dd, Jx = 6.5 Hz, J2 = 2.8 Hz), 3.45 (1H, m), 4.29 (HH, m), 4.35 (HH, dd, J1 = 9.7 Hz, J2 = 2.8 Hz), 5.88 (HH, d, J = 5.6 Hz), 5.98 (HH, d, J = 5.6 Hz), 7.07 (1H, s), 8.06 (HH, s), 8.34 (HH, s). MS (TS): 448 (M + + H) Example 4 (SS, 5R, 6S-6- ((IR) -1-hydroxyethyl) -l-methyl-2- (6-methylimidazo) [5, 1-b] thiazolium-2-yl) -l-carbapen-2-em-3-carboxylate (internal salt) a) Yodide of (SS, 5R, 6S) -6- ((IR) -1- hydroxyethyl) -1-methyl-2- (6-methylimidazo [5, 1-b] thiazolium-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl To a solution of 64.7 milligrams of ( 1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3 4-Nitrobenzylcarboxylate in 1 milliliter of dry dichloromethane 0.86 milliliter of iodomethane was added, and the mixture was stirred under the argon atmosphere in the dark at room temperature for 21 hours. Evaporation of the unreacted reagent under reduced pressure afforded (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (6-methylimidazo [5, 1-b] thiazolium-2 -l) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (DMSO-dg) d: 1.18 (3H, d, J = 6.6 Hz), 1.22 (3H, d, J = 7.4 Hz), 3.49 (HH, dd), 3.73 (HH, m), 4.05 (1H, m), 4.07 (3H, s), 4.39 (IH, dd), 5.18 (IH, d), 5.39 (IH, d, J = 14.3 Hz), 5.51 (IH, d, J = 14.3 Hz ), 7.72 (2H, d, J = 8.8 Hz), 7.80 (1H, s), 8.22 (2H, d, J = 8.8 Hz), 8.61 (HH, s), 9.51 (HH, s). b) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (6-methylimidazo [5, 1-b] thiazolium-2-yl) -l-carbapen- 2-em-3-carboxylate (internal salt) The total volume of the iodide of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (6-methylimidazo [5, 1-b] thiazolium-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl was dissolved in a mixture of 2 milliliters of THF and 2 milliliters of a phosphate stabilizer of 1/15 M ( pH of 6.8), 77 milligrams of 10 percent Pd-C were added. The reactor was purged with hydrogen, and the reaction mixture was stirred at room temperature for 5 hours. The catalyst was collected by filtration with Celite and washed with water. The filtrate was washed with 20 milliliters of ethyl acetate and purified by column chromatography on DIAION HP-20 to provide 14.1 milligrams of the header compound.

Nuclear magnetic resonance (D20) d: (HOD = 4.80ppm): 1.23 (3H, d, J = 7.1 Hz), 1.30 (3H, d, J = 6.3 Hz), 3.53 (ÍH, dd, Ji = 6.1 Hz, J2 = 2.5 Hz), 4.06 (3H, s), 4.28 (2H, m), 7.47 (HH, s), 8.05 (HH, s), 9.10 1H, s).

Example 5 Acid (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -1-methyl-1-carbapen-2-em -3-carboxylic acid a) (SS, 5R, 6S) -6- ((IR) -l-hydroxyethyl-2- (imidazo [5, 1-b] thiazol-3-yl) -l-methyl-l-carbapen -2-em-3-carboxylate of 4-nitrobenzyl To a solution of 491 milligrams of (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2-oxo-l 4-nitrobenzylcarbapenam-3-carboxylate in 12 milliliters of dry acetonitrile was added dropwise 0.59 milliliter of N, N-diisopropylethylamine followed by 0.227 milliliter of anhydrous trifluoromethanesulfonic acid under the argon atmosphere at -15 ° C. The reaction mixture was stirred at the same temperature for 30 minutes, diluted with 40 milliliters of ethyl acetate and washed sequentially with the semi-saturated aqueous saline solution, a mixed solvent of the semi-saturated aqueous solution and hydrochloric acid. aqueous solution (pH 1.1), a mixed solvent of the semi-saturated aqueous saline solution and saturated aqueous sodium hydrogen carbonate (pH of 8.9), and the semi-saturated aqueous saline solution. The organic layer was dried through anhydrous magnesium sulfate, filtered and the solvent was removed under reduced pressure. The residue obtained in this way was dissolved in 4 milliliters of dry N-methylpyrrolidinone, mixed with 37 milligrams of tri-2-furylphosphine, 370 milligrams of zinc chloride, 37 milligrams of tris (dibenzylidene ketone) dipalladium (O), and a solution of 765 milligrams of 3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole in 2 milliliters of dry N-methylpyrrolidinone and the mixture was stirred under an argon atmosphere at 50 ° C for 40 minutes. The reaction mixture was diluted with 200 milliliters of ethyl acetate and 200 milliliters of water, and the organic layer was separated. The organic layer was diluted with 100 milliliters of semi-saturated aqueous sodium hydrogen carbonate and stirred for 30 minutes to remove the insoluble materials by filtration. The organic layer of the filtrate was separated, washed three times with 200 milliliters of the semi-saturated aqueous saline solution, dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained in this way was purified by silica gel column chromatography (chloroform: methanol = 30: 1) to provide 225 milligrams of (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo - - [5, 1-b] thiazol-3-yl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (CDCI3) d: 1.16 (3H, d, J = 7.2 Hz), 1.36 (3H, d, J = 6.3 Hz), 3.48 (HH, dd, J1 = 5.9 Hz, 3.2 Hz), 3.65 (HH) , m, 4.34 (HH, m), 4.55 (HH, dd, J1 = 10.4 Hz, J2 = 3.2 Hz), 5.12 (1H, d, J = 13.4 Hz), 5.30 (HH, d, J = 13.4 Hz) , 6.98 (HH, s), 7.06 (HH, s), 7.35 (2H, d, J = 8.9 Hz), 7.89 (HH, s), 8.12 (2H, d, J = 8.9 Hz) b) Acid ( ÍS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-methyl-l-carbapen-2-em-3 -carboxylic To a solution of 4.70 grams of (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -1-methyl 4-nitrobenzyl-l-carbapen-2-em-3-carboxylate in 10 milliliters of THF and 10 milliliters of a 1/15 M phosphate stabilizer were added 240 milligrams of 10 percent Pd-C. The reactor was purged with hydrogen, and the reaction mixture was stirred at room temperature for 3 hours. The catalyst was collected by filtration and washed with water. The filtrate was washed with ethyl acetate, and the aqueous layer was purified by column chromatography on DIAION HP-20 to provide 27.5 milligrams of the header compound. Nuclear magnetic resonance (D20) d: (HOD = 4.80ppm): 1.16 (3H, d, J = 7.1 Hz), 1.32 (3H, d, J = 6.3 Hz), 3.50 - 3.65 (2H, m), 4.25 - 4.48 (2H, m), 7.42 (H, s), 7.45 (H, s), 8.70 (H, s).

Example 6 (SS, 5R, 6S) -6- ((1R) -l-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-methyl-l-carbapen-2-em- Pivaloyloxymethyl 3-carboxylate To a suspension of 32.5 milligrams of the acid (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-methyl-l-carbapen-2-em-carboxylic acid in a mixture of 10 milliliters of water and 8 milliliters of methanol was added 7.8 milligrams of sodium hydrogen carbonate, and the mixture was stirred at room temperature for 10 minutes to form a solution The methanol was removed under reduced pressure, and the residue was lyophilized. The lyophilized product was dissolved in 2 milliliters of dry DMF, 0.03 milliliter of iodomethyl pivalate was added under the argon atmosphere at -30 ° C, and the mixture was stirred for 2 hours during which time the temperature was raised to -10 °. C. Ethyl acetate was added to the reaction mixture, and the mixture was washed with a semi-saturated aqueous saline solution. The organic layer was dried through anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to a total volume of 3 milliliters. The residue obtained in this way was purified by column chromatography on silica gel (chloroform: methanol = 30: 1-10: 1) to provide 26.6 milligrams of the header compound. Nuclear magnetic resonance (CDCI3) d: 1.14 (3H, d, J = 7. 4 Hz), 1.17 (9H, s), 1.37 (3H, d, J = 6.3 Hz), 3.43 (1H, dd, Ji = 6.3 Hz, J2 = 3.1 Hz), 3.70 (HI, m), 4.32 (HI) , m), 4.48 (ÍH, dd, Ji = 10.4 Hz, J2 = 3.1 Hz), 5.74 (ÍH, d, J = . 5 Hz), 5.87 (1H, d, J = 5.5 Hz), 7.07 (HH, s), 7.13 (HH, s), 7.85 (HH, s).

Example 7 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (6-methylimidazo [5, 1-b] thiazolium-3-yl) -l-carbapen-2- em-3-carboxylate (internal salt) a) Iodide of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -1-methyl-2- (6-methylimidazo [5, 1-b] thiazolium-3-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl To a suspension of 102 milligrams of (1S, 5R, 6S) -6- ((1-R-1-hydroxyethyl-2- ( Imidazo [5, 1-b] thiazol-3-yl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and 1.5 milliliters of dry dichloromethane were added 2.7 milliliters of iodomethane, and the mixture was stirred under an argon atmosphere in the dark at room temperature - for 3 days. The unreacted reagent was removed under reduced pressure to provide 122 milligrams of (SS, 5R, 6S) -6- ((IR) -l-hydroxyethyl-1-methyl-2- (6-methylimidazo) iodide., 1-b] thiazolium-3-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (DMSO-dg) d: 1.06 (3H, d, J = 7.6 Hz), 1.17 (3H, d, J = 6.3 Hz), 3.55 (1H, dd, Ji = 5.5 Hz, J2 = 3.2 Hz) , 3.66 (HH, m), 3.94 (HH, m), 3.98 (3H, s), 4.44 (1H, dd, Ji = 10.5Hz, J2 = 3.2 Hz), 5.19 (HH, d, J = 13.4 Hz) , 5.28 (HH, d, J = 13.4 Hz), 7.49 (2H, d, J = 8.8 Hz), 7.72 (HH, s), 7.82 (HH, s), 8.19 (2H, d, J = 8.8 Hz) , 9.73 (ÍH, s). b) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (6-methylimidazo [5, 1-b] thiazolium-3-yl) -l-carbapen- 2-em-3-carboxylate (inner salt) To a solution of 60.5 milligrams of (1S, 5R, 6S) -6- ((IR) -l-hydroxyethyl-1-methyl-2- (6-methylimidazo [5, 1-b] thiazolium-3-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 1.8 milliliters of THF and 1.8 milliliters of a phosphate stabilizer, 1/15 M (pH of 6.8) is they added 71 milligrams of 10 percent Pd-C, the reactor was purged with hydrogen, and the reaction mixture was stirred at room temperature for 3.5 hours.The catalyst was collected by filtration through Celite, and washed with water. The filtered material was washed - - with 20 milliliters of ethyl acetate, and purified by column chromatography on DIAION HP-20 and on COSMOSEAL 40C18-PREP (water: methanol = 20: 1) to provide 8.3 milligrams of the header compound. Nuclear magnetic resonance (D20) d: (HOD = 4.80ppm): 1.14 (3H, d, J = 7.4 Hz), 1.31 (3H, d, J = 6.3 Hz), 3.55 (HH, m), 3.62 (HH, dd, J, L = 5.8 Hz, J2 = 2.9 Hz), 4.06 (3H, s), 4.30 (HH, m), 4.43 (HH, dd, J1 = 9.9 Hz, J2 = 2.9 Hz), 7.52 (ÍH, s), 7.61 (ÍH, s), 9.06 (1H, s).

Example 8 Acid (5R, 6S-6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylic acid a) ( 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylic acid 4-nitrobenzoyl ester To the ice-cooled solution of 149 milligrams of (3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-oxo-l-carbapenam-3-carboxylate 4-nitrobenzyl in 4 milliliters of acetonitrile dry 0.187 milliliter of N, N-diisopropylethylamine was added dropwise, followed by 0.071 milliliter of anhydrous trifluoromethanesulfonic acid under the argon atmosphere. The solution was stirred at the same temperature for 30 minutes, diluted with ethyl acetate and washed in - - sequence with a mixed solvent of a semi-saturated aqueous saline solution and saturated aqueous sodium hydrogen carbonate (pH of 8.9), and the semi-saturated aqueous saline solution. The organic layer was dried through anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure. The residue obtained in this way was dissolved in 2 milliliters of dry N-methylpyrrolidinone, then 12 milligrams of tri-2-furylphosphine, 116 milligrams of zinc chloride, 12 milligrams of tris (dibenzylidene ketone) dipalladium (0) and a solution were added. of 306 milligrams of 2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole in 1 milliliter of dry N-methylpyrrolidinone, and the mixture was stirred under an argon atmosphere at 50 ° C for 2 hours. The reaction mixture was diluted with 50 milliliters of ethyl acetate and 50 milliliters of water, and the insoluble materials were removed by filtration and washed with ethyl acetate. The organic layer of the filtrate was separated, dried through anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue obtained in this way was purified by column chromatography on Sephadex LH-20 (chloroform: methanol = 1: 1). The fraction containing the desired product was concentrated under reduced pressure, and triturated with 13 milliliters of diethyl ether to collect the insoluble materials and thus provide 38.5 milligrams of (5R, 6S) -6- ((IR) -1 -hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (DMSO-dg) d: 1.17 (3 H, d, J = 6.2 Hz), 3.31 (H, m), 3.40 - 3.55 (3 H, m), 4.01 (1 H, m), 4.24 (H, m ), 5.15 (HH, d, J = 4.9 Hz), 5.41 (HH, d, J = 14.0 Hz), 5.53 (HH, d, J = 14.0 Hz), 7.04 (1H, s), 7.75 (2H, d , J = 8.9 Hz), 8.24 (2H, d, J = 8.9 Hz), 8.28 (HH, s), 8.37 (HH, s). b) Acid (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo) [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylic acid To a solution of 41 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) - 2- (imidazo [5, 1-b] thiazol-2-yl) -1-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 2 milliliters of THF and 2 milliliters of a phosphate stabilizer 1/15 M (pH of 6.8) 61 milligrams of 10 percent Pd-C were added. The reactor was purged with hydrogen, and the reaction mixture was stirred at room temperature for 2 hours. The catalyst was removed by filtration in Celite and washed with water. The filtrate was washed with ethyl acetate and the aqueous layer was purified by column chromatography on DIAION HP-20 to provide 5.7 milligrams of the header compound.

- Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1.31 (3H, d, J = 6.3 Hz), 3.30 (2H, m), 3.53 (ÍH, dd, Jx = 5.9 Hz, J2 = 3.0 Hz), 4.26 (2H, m), 7.37 (HH, s), 7.89 (HH, s), 8.88 (1H, s).

Example 9 Acid (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (3-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2 -em-3-carboxylic acid a) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (3-methylimidazo [5, 1-b] thiazol-2-yl ) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl To a solution of 353.2 milligrams of (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl- 4-Nitrobenzyl 2-oxo-l-carbapenam-3-carboxylate in 7 milliliters of dry acetonitrile was added dropwise 0.34 milliliter of N, N-diisopropylethylamine, followed by 0.18 milliliter of anhydrous trifluoromethanesulfonic acid under the atmosphere of argon at -15. ° C. After the reaction mixture was stirred at the same temperature for 30 minutes, it was diluted with 10 milliliters of ethyl acetate, washed sequentially with a semi-saturated aqueous saline solution, a mixed solution of the semi-aqueous aqueous saline solution. saturated and 1 N hydrochloric acid, a mixed solution of the solution - - semi-saturated aqueous salt and saturated aqueous sodium hydrogen carbonate and the semi-saturated aqueous saline solution. The organic layer was dried through anhydrous magnesium sulfate, filtered, mixed with 2 milliliters of dry N-methylpyrrolidinone, and the ethyl acetate was removed under reduced pressure. To the residue were added a solution of 26.8 milligrams of tris (dibenzylideneacetone) dipalladium (O), 27.2 milligrams of tri-2-furylphosphine and 470 milligrams of 3-methyl-2- (tri-n-butyl-stanyl) imidazo [5, 1-b] thiazole in 0.5 milliliter of dry N-pyrrolidinone, 0.5 milliliter, and 266 milligrams of zinc chloride and the mixture was stirred under an argon atmosphere at 50 ° C for 1 hour. The solvent was concentrated under reduced pressure, diluted with -20 milliliters of ethyl acetate and 80 milliliters of water, and adjusted to weak alkaline with saturated aqueous sodium hydrogen carbamate. The insoluble materials were collected by filtration, the residue was dissolved in acetone, and the soluble materials were concentrated. In addition, the organic layer of the filtrate was separated, washed once with 20 milliliters of saturated aqueous saline solution, combined with the soluble acetone materials, dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. . The residue was purified by column chromatography on silica gel (ethyl acetate - - methanol = 95: 5) to provide 5.71 grams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (3-methylimidazo) [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (CDCI3) d: 1.11 (3H, d, J = 7. 3 Hz), 1.30 (3H, d, J = 6.3 Hz), 2.14 (3H, s), 3.31 - 3.41 (2H, m), 4.26 (HH, m), 4.39 (HH, dd, Ji = 10.2 Hz, J2 = 3.6 Hz), 5.13 (1H, d, J = 13.7 Hz), 5.33 (ÍH, d, J = 13. 7), 7.02 (HH, s), 7.43 (2H, d, J = 8.5 Hz) 7.80 (HH, s), 8.05 (2H, d, J = 8.5 Hz). MS (FAB +): 4.83 (M + + H). b) Acid (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -1-methyl-2- (3-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen -2-em-3-carboxylic acid To a solution of 157.3 milligrams of (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (3-methylimidazo [5, 1- b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 3 milliliters of THF and 3 milliliters of a 1/15 M phosphate stabilizer (pH of 6.8) was added 0.24 gram. from Pd-C to 10 percent. The reactor was purged with hydrogen, the reaction mixture was stirred at room temperature for 1 hour. The catalyst was collected by filtration, and washed with 50 milliliters of water. The filtrate was diluted with 20 milliliters of ethyl acetate, separated and the organic layer washed. additionally with water. The combined aqueous layer was concentrated under reduced pressure to a volume of about 30 milliliters. The residual concentrated material was purified by column chromatography on DIA 0N HP-20. The fraction containing the desired product was lyophilized to provide 63.5 milligrams of the header compound. Nuclear magnetic resonance (D20) d: (HOD = 4.80 ppm): 1.16 (3H, d, J = 7.1 Hz), 1.30 (3H, d, J = 6.3 Hz), 2.38 (3H, s), 3.40 (ÍH, m), 3.57 (1H, m), 4.28 (HH, m), 4.38 (1H, dd, J = 9.7 Hz, J2 = 3.0 Hz), 7.50 (1H, s), 9.00 (HH, s). MS (FAB +) -: 348 (M + + H) Example 10 (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (3-methylimidazo) Pivaloyloxymethyl [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate To a solution of 29.4 milligrams of (1S, 5R, 6S) - 6- ((IR) -1 -hydroxyethyl) -l-methyl-2- (3-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate in 0.8 milliliter of dry DMF was added 0.017 milliliter of iodomethyl pivalate under the argon atmosphere at -30 ° C, and the mixture was stirred for 4 hours during which period of time the temperature rose to 10 ° C. The reaction mixture was diluted with 10 milliliters of ethyl acetate, dried and the aqueous layer was extracted twice with ethyl acetate, while the organic layer was washed with 10 milliliters of the semi-saturated aqueous saline solution. The combined organic layer was dried through anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to a volume of 1 milliliter. The residue obtained in this way was purified by silica gel column chromatography (chloroform: methanol = 20: 1) and in Sephadex LH-20 (dichloromethane: methanol = 1: 1) in this sequence to provide 7.9 milliliters of the Heading .. Nuclear Magnetic Resonance (CDCI3) d: 1.02 (9H, s), 1.09 (3H, d, J = 7.4Hz), 1.29 (3H, d, J = 6.3Hz), 3.27-3.34 (2H,), 4.24 (1H, m), 4.33 (1H, dd, J? = 9.7Hz, J2 = 2.8Hz), 5.69 (1H, d, J = 5.5Hz), 5.82 (HI, d, J = 5.5Hz), 7.02 (ÍH, s), 7.88 (ÍH, s).

Example 11 (SS, 5R, 6S) -2- (3, 6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- 2-em-3-carboxylate (internal salt) - - a) Iodide of (SS, 5R, 6S) -2- (3,6-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl- l-carbapen-2-em-3-carboxylic acid 4-nitrobenzyl _ To a solution of 73.6 milligrams of (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- ( 3-Methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 0.5 milliliter of dry dichloromethane 0.95 milliliter of iodomethane was added, and the mixture was stirred under the argon atmosphere in the dark at room temperature for 18 hours. The unreacted reagent was removed under reduced pressure to provide 89.1 milligrams of (SS, 5R, 6S) -2- (3,6-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ( IR) -1-hydroxyethyl-l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl, nuclear magnetic resonance (CD3? D) d: 0.99 (3H, d, J = 7.4 Hz), 1.09 (3H, d, J = 6.0Hz), 2.10 (3H, s), 3.10 (111, m), 3.92 (3H, s), 3.98 (1H, m), 4.29 (1H, dd, j '? = 10.5 Hz, J2 = 3.0Hz), 5.02 (1H, d, J = 13.1Hz), 5.15 (111, d, J = 13.1Hz), 7.34 (2H, d, J = 8.5Hz), 7.54 (1H, s) 7.89 (2H, d, J = 8.5Hz), 9.26 (lH, s) b) (SS, 5R, 6S) -2- (3, 6-dimethylimidazo [5, 1-b] thiazolium-2-yl) ) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate (inner salt) To a solution of 89.1 milligrams of iodide (ΔS, 5R, 6S) - 2- (3, 6-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- - - ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 2 milliliters of THF and 2 milliliters of a phosphate stabilizer 1/15 M (pH of 6.8 ) 102.7 milligrams of 10% Pd-C were added. The reactor was purged with hydrogen, the reaction mixture was stirred at room temperature for 5 hours. The catalyst was collected by filtration and washed with water. The filtrate was diluted with 20 milliliters of ethyl acetate, 20-milliliters were separated and the organic layer was further washed with water. The combined aqueous layer was concentrated under reduced pressure to a volume of about 30 milliliters. The concentrated material was purified by column chromatography on DIAION HP-20 to provide 17.0 milligrams of the header compound. Nuclear magnetic resonance (D 0) d (HOD = 4.80 ppm): 1.16 (3H, d, J = 7.2Hz), 1.30 (3H, d, J = 6.3Hz), 2.37 (3H, s), 3.40 (1H, m), 3.58 (1H, m), 4.09 (3H, s), 4.28 (1H, m), 4.39 (1H, dd, J? = 9.8Hz, J2 = 2.2Hz), 7.58 (H, s), 9.22 (ÍH, s).

Example 12 Acid (5R, 6S) -6- ((IR) -l-hydroxyethyl-2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylic acid - a) (5R, 6S) -6- ((IR) -l-hydroxyethyl-2-imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate from 4- Nitrobenzyl To a water-cooled solution of 493 milligrams of (3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl in 13 milliliters of dry acetonitrile 13 milliliters were added by drops 0.619 milliliter of N, N-diisopropylethylamine, followed by 0.235 milliliter of anhydrous trifluoromethanesulfonic acid under the argon atmosphere. After the reaction mixture was stirred at the same temperature for 30 minutes, it was diluted with ethyl acetate, and washed with a semi-saturated aqueous saline solution, a mixed solution of the semi-saturated aqueous saline solution and hydrochloric acid. of 1 N (pH of 1.1), a mixed solution of the semi-saturated aqueous saline solution and saturated aqueous sodium hydrogen carbonate (pH of 8.9), and the semi-saturated aqueous saline solution in this sequence. The organic layer was dried through anhydrous magnesium sulfate, filtered and the solvent was removed under reduced pressure. The residue obtained in this manner was dissolved in 5 milliliters of dry N-methylpyrrolidinone, mixed with 40 milligrams of tri-2-furylphosphine, 384 milligrams of zinc chloride, 40 milligrams of tris (dibenzylidenacetone) dipalladium (O), and 950 milligrams. from - - 3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole in 2 milliliters of dry N-methyl-pyrrolidinone, and the mixture was stirred under an argon atmosphere at 50 ° C for 1.5 hours. The reaction mixture was diluted with 50 milliliters of ethyl acetate and 50 milliliters of semi-saturated aqueous sodium hydrogen carbonate, the insoluble materials were removed by filtration, and the filtered material was washed with ethyl acetate. The organic layer of the filtrate was separated, dried through anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue obtained in this way was purified by column chromatography on silica gel (chloroform: methanol = 15: 1) to provide 303 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (CDCI3) d: 1.40 (3H, d, J = 6.3Hz), 3.38 (3H, m), 4.33 (1H, m), 4.44 (1H, m), 5.22 (111, d, J = 13.2 Hz), 5.36 (1H, d, J = 13.2Hz), 7.06 (1H, s), 7.09 (1H, s), 7.43 (2H, d, J = 8.9Hz), 7.75 (1H, s), 8.18 ( 2H, d, J = 8.9Hz). b) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylic acid _ To a solution of 203 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -1-carbapen-2- 4-nitrobenzyl em-3-carboxylate in 4 - - milliliters of THF and 4 milliliters of a 1/15 M phosphate stabilizer (pH of 6.8) were added with 152 milligrams of 10 percent Pd-C. The reactor was purged with hydrogen, the reaction mixture was stirred at room temperature for 1 hour. The catalyst was collected by filtration on Celite, and washed with water. The filtrate was washed with ethyl acetate, and then the aqueous layer was purified by column chromatography on DIAION HP-20, followed by crystallization of 1 milliliter of water to provide 32.8 milligrams of the header compound. Nuclear Magnetic Resonance (DMSO-dg) d: 1.17 (3H, d, J = 6.3Hz), 3.20 (1H, m), 3.55 (2H, m), 3.99 (1H, m), 4.28 (1H, m), 5.14 (1H, m), 7.06 (1H, s), 7.34 (1H, s), 7.99 (HH, s).

Example 13 (5R, 6S) -6- ((IR) -l-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of pivaloyloxymethyl A a suspension of 42.1 milligrams of acid (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylic acid of 10 milliliters of water, 1.3 milliliters of an aqueous sodium hydrogen carbonate solution of 0. IN was added, and the mixture was stirred at room temperature for 1 hour to form a - solution, which was then lyophilized. The lyophilized product was dissolved in 1 milliliter of dry DMF, 0.034 milliliter of iodomethyl pivalate was added under the argon atmosphere at -30 ° C, and the mixture was stirred for 1.5 hours during which time the temperature was raised to - 10 ° C. The reaction mixture was diluted with 20 milliliters of ethyl acetate, and washed with a semi-saturated aqueous saline solution. The organic layer was dried through anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to a volume of 3 milliliters. The residue obtained in this way was purified by silica gel column chromatography (chloroform: methanol = 15: 1) and in Sephadex LH-20 (chlororormo: methanol = 1: 1) in this sequence to provide 27.2 milligrams of the header. Nuclear Magnetic Resonance (CDCI3) d: 1.19 (9H, s), 1.38 (3H, d, J = 6.2Hz), 3.37 (2H, m), 4.29 (1H, m), 4.42 (1H, m), 5.78 ( 1H, d, J = 5.5 Hz), 5.88 (1H, d, J = 5.5Hz), 7.13 (2H, s), 7.8.0 (1H, s).

Example 14 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (6-methylimidazo [5, 1-b] thiazolium-3-yl) -l-carbapen-2-em-3-carboxylate ( internal salt] To a suspension of 100 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -1-carbapen- 4-Nitrobenzyl 2-em-3-carboxylate in 1.5 milliliters of dry dichloromethane was added 1.37 milliliters of iodomethane and the mixture was stirred under an argon atmosphere in the dark at room temperature for 24 hours. reduced pressure The residue obtained in this manner was dissolved in 4 milliliters of THF and 4 milliliters of a 1/15 M phosphate stabilizer (pH of 6.8), and 160 milligrams of 10 percent Pd-C were added. it was purged with hydrogen, the reaction mixture was stirred at room temperature for 3.5 hours, the catalyst was collected by filtration on celite and washed with water, the filtrate was stirred with ethyl acetate and purified medium. before column chromatography in DIAION HP-20 and COSMOSEAL 40C18-PREP (water: methanol = 20: 1) to provide 4.8 milligrams of the header compound. Nuclear magnetic resonance (D20) d: (HOD = 4.80 ppm): 1.31 (3H, d, J = 6.5Hz), 3.25 (1H, m), 3.45 (1H, m), 3.60 (1H, dd, J? = 6.0Hz, J2 = 3.2Hz), 4.08 (3H, s), 4.28 (1H, m), 4.39 (1H, m), 7.49 (1H, s), 7.62 (1H, s), 8.93 (1H, s) .

Example 15 - (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (6-methylimidazo [5, 1-b] thiazolium-2-yl) -l-carbapen-2-em-3-carboxylate ( internal salt) a) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (6-methylimidazo [5, 1-b] thiazolium-2-yl) -l-carbapen-2 iodide -em-3-carboxylated 4-nitrobenzyl A 51.6 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) - 4-Nitrobenzyl l-carbapen-2-em-3-carboxylate, 1.5 milliliters of iodomethane were added, and the mixture was stirred under an argon atmosphere in the dark at room temperature for 2 days. The unreacted reagent was removed under reduced pressure to provide 59.5 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (6-methylimidazo [5, 1-b] thiazolium-2-yl) -l-carbapen-2-em-3-carboxylate from 4-Nitrobenzyl. Nuclear Magnetic Resonance (DMSO-dg) d: 1.18 (3H, d, J = 6.2Hz), 3.45 (2H, m), 3.58 (IH, dd, J? = 5.8Hz, J2 = 3.1Hz), 4. 05 (1H, m) 4.07 (3H, s) 4.31 (1H, m 5.44 (1H, d, J = 13.5Hz), 5.55 (1H, d, J = 13.5Hz), 7.75 (2H, d, J = 8.8Hz), 7.8K1H, s), 8.25 (2H, d, J = 8.8Hz), 8.59 ( 1H, s), 9.53 (1H, s). b) 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (6-methylimidazo) [5, 1-b] thiazolium-2-yl) -l-carbapen-2-em-3-carboxylate (internal salt) - - To a solution of 58 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (6-methylimidazo [5, 1-b] thiazolium-2-yl) -l-carbapenyl iodide -2-em-3-carboxylate of 4-nitrobenzyl in 2 milliliters of THF and 2 milliliters of a 1/15 M phosphate stabilizer (pH of 6.8) were added 68 milligrams of 10 percent Pd-C. The reactor was purged with hydrogen, and the reaction mixture was stirred at room temperature for 4 hours. The catalyst was collected by filtration on Celite, and washed with water. The filtrate was washed with ethyl acetate, the aqueous layer was purified by column chromatography on DIAION HP-20 to provide 5.4 milligrams of the header compound. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.29 (3H, d; J = 6.5Hz), 3.31 (2H, m), 3.53 (ÍH, dd, J? = 5.8Hz, J2 = 3.0Hz), 4.05 (3H, s), 4.25 (2H, m), 7.47 (1H, s ), 7.90 (1H, S), 9.09 (1H, s).

Example 16 (SS, 5R, 65) -2- (6-Carbomoylmethylimidazo [5, 1-b] thiazolium-2-yl) 6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em -3-carboxylate (internal salt) - a) (1S, 5R, 6S) -2- (6-carbamoylmethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- 4-Nitrobenzyl 2-em-3-carboxylate In the same manner as in Example 88-a) which will be described below, the (1S, 5R, 6S) -2- (6-carbamoylmethylimidazo [5S] iodide was obtained. , 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl of 64.3 milligrams of (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (DMSO-dg) d: 1.18 (3H, d, J = 6.3Hz), 1.22 (3H, d, J = 7.2Hz), 3.50 (HH, dd, J! = 5.7Hz, J2 = 3.0Hz ), 3.72 (1H, m), 4.05 (1H, m), 4.38 (1H, m), 5.18 (2H, s), 5.40 (1H, d, J = 13.8Hz), 5.51 (1H, d, J = 13.8Hz), 7.59 (1H, s), 7.71 (2H, d, J = 9.9Hz), 7.83 (2H, m), 8.22 (2H, d, J = 9.DHz), 8.64 (1H, s), 9.54 (1H, s). b) (SS, 5R, 6S) -2- (6-carbamoylmethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen- 2-em-3-carboxylate (inner salt) In the same manner as in Example 4-b), 58.6 milligrams of the header compound were obtained from the total amount of iodide of (ΔS, 5R, 6S) -2- ( 6-carbamoylmethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1- - hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl obtained above. Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1. 26 (3H, d, J = 7.2Hz), 1.31 (3H, d, J = 6.4Hz), 3.57 (1H, dd, Jl = 6.1Hz, J2 = 2.8Hz), 3.66 (1H, m), 4.28 (lH, m), 4.36 (1H, dd, Jl = 9.3Hz, J2 = 2.8Hz), 5.25 (2H, s), 7.57 (lH, s), 8.13 (1H, s), 9.25 (1H, s).

Example 17 Acid (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (5-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2 -em-3-carboxylic acid a) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (5-methylimidazo [5, 1-b] thiazol-2-yl ) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), 433 milligrams of (1S, 5R, 6S) -6- ((IR) - were obtained 1-hydroxyethyl) -l-methyl-2- (5-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate from 4-nitrobenzyl from 724 milligrams of (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -1-methyl-2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 1.04 grams of 5-methyl-2 - (tri-n-butylstannyl) imidazo [5, 1-b] thiazole of 4-nitrobenzyl.

- Nuclear magnetic resonance (CDCI3) d: 1.30 (3H, d, J = 7.4Hz), 1.39 (3H, d, J = 6.3Hz), 2.59 (3H, s), 3.36 (1H, dd, J1 = 6.5Hz, J2 = 2.8Hz), 3.46 (1H, m), 4.32 (1H,), 4.37 (1H, dd, Jl = 9.6Hz, J2 = 2.8Hz), 5.27 (ÍH, d, J = 13.8Hz), 5.53 ( ÍH, d, J = 13.8Hz), 6.92 (1H, s), 7.67 (2H, d, J = 8.7Hz), 8.19 (1H, s), 8.22 (2H, d, J = 8.5Hz). b) Acid (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -1-methyl-2- (5-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen -2-em-3-carboxylic acid In the same manner as in Example 5-b), 98.5 milligrams of the header compound of 326 milligrams of (IS, 5R, 6S) -6- ((IR) -1- were obtained. hydroxyethyl) -1-methyl-2- (5-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-3-em-3-carboxylate. Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1.21 (3H, d, J = 7.1Hz), 1.29 (3H, d, J = 6.4Hz), 2.77 (3H, s), 3.51 (ÍH, dd) , J2 = 2.7Hz), 3.60 (HH,), 4.27 (2H, m), 7.25 (1H, s), 7.92 (1H, s).

Example l (SS, 5R, 6S) -2- (5, 6-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- 2-em-3-carboxylate (internal salt) - - In the same manner as in Example 14 with the exception that the purification was carried out by column chromatography on DIAION HP-20, 19.1 milligrams of the header compound were obtained from 107 milligrams of (IS, 5R, 6S ) -6- ((IR) -1-hydroxyethyl) -1-methyl-2- (5-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of 4 nitrobenzyl. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.26 (3H, d, J = 7.1Hz), 1.31 (3H, d, J = 6.4Hz), 2.78 (3H, s), 3.55 (1H, dd) , J ^ d.lHz, J2 = 2.8Hz), 3.64 (1H, m), 3.92 (3H, s), 4.28 (HH, m), 4.33 (1H, dd, 7.37 (HH, s), 7.97 (1H , s).

Example 19 (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (5-methylimidazo) [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of pivaloyloxymethyl To a solution of 46.8 milligrams of the acid (IS, 5R, 6S) -6- ((IR) - 1-hydroxyethyl) -l-methyl-2- (5-methylimidazo [5, 1-b] thiazol-2-yl-l-carbapen-3-em-carboxylic acid of 5 milliliters of water was added 134 milliliters of a solution of 0.1 N aqueous sodium hydrogen carbonate. The mixture was lyophilized, dissolved in 1 milliliter of DMF, added with 0.034 milliliter of pivaloyloxymethyl iodide under an argon atmosphere at -30 ° C, and stirred at the same temperature. for 1.5 hours The reaction mixture was diluted with 50 milliliters of ethyl acetate, and washed with 50 milliliters of a semi-saturated aqueous saline solution.The organic layer was dried through anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to a volume of 1 milliliter The residue obtained in this way was purified by column chromatography on silica gel (dichloromethane: m ethanol = 20: 1) and Sephadex LH-20 (chloroform: methanol = 1: 1) in this sequence to provide 44.5 milligrams of the header compound. Nuclear Magnetic Resonance (CDCI3) d: 1.21 (9H, s), 1.28 (3H, d, J = 7.1Hz), 1.37 (3H, d, J = 6.3Hz), 2.63 (3H, s), 3.32 (ÍH, dd, J2 = 2.8Hz), 3.44 (HH, m), 4.31 (2H,), 5.87 HH, d, J = 5.6Hz), 5.99 (1H, d, J = 5.6Hz), 6.92 (HH, s) , 8.16 (1H, s).

Example 20 Acid (1S, 5R, 6S) -2- (7-chloroimidazo [5,,? -b] thiazol-1-yl) -6- ((1R) -1-hydroxyethyl) -1 --methyl-1-carbapen- • 2- • em-3-carboxylic a) (ÍS, 5R, 6S) -2- (7-chloroimidazo [5, 1-b] thiazol-2-yl) 6 - ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), 183 milligrams of (I s) were obtained , 5R, 6S) -2- (7-chloroimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -1-methyl-l-carbapen-2-em- 3-Nitrobenzyl 3-carboxylate and 1.07 grams of 7-chloro-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole of 4-nitrobenzyl. Nuclear magnetic resonance (CDCI3) d: 1.31 (3H, d, J = 7.4Hz), 1.40 (3H, d, J = 6.3Hz), 3.37 (ÍH, dd, J? = 6.5Hz, J2 = 2.7Hz), 3.46 (1H, m), 4.35 (2H, m), 5.28 (1H, d, J = 13.5Hz), 5.52 (1H, d, J = 13.5Hz), 7.68 (2H, d, J = 8.9Hz), 7.89 (1H, s), 8.24 (2H, d, J = 8.9Hz)), 8.27 (1H, s). b) Acid (SS, 5R, 6S-2- (7-chloroimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen- 2-em-3-carboxylic acid In the same manner as in Example 5-b), 8.2 milligrams of the header compound were obtained from 134 milligrams of (IS, 5R, 6S) -2- (7-chloroimidazo [5 , 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D 0) d (H0D = 4.80 ppm): 1.22 (3H, d, J = 7.1Hz), 1.32 (3H, d, J = 6.3Hz), 3.53 (2H,), 4.29 (2H, m ), 7.81 (1H, s), 7.98 (1H, s).

Example 21 - - Acid (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (2-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2 -em-3-carboxylic acid a) (1S, 5R, S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (2-methylimidazo [5, 1-b] thiazol-3-yl ) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), 40.4 milligrams of (ΔS, 5R, 6S) -6- ((IR) - were obtained 1-hydroxyethyl) -l-methyl-2- (2-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate from 4-nitrobenzyl from 190 milligrams of (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -1-methyl-2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 272 milligrams of 2-methyl-3 - (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear Magnetic Resonance (DMSO-dg) d: 1.00 (3H,), 1.17 (3H, d, J = 6.1Hz), 2.14 (3H, s), 3.56 (1H,), 3.78 (1H, m), 4.06 ( 1H, m), 4.55 (1H, m), 5.10-5.40 (3H, m), 7.00 (1H, m), 7.50-7.70 (2H, m), 8.12-8.28 (3H, m). b) Acid (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -1-methyl-2- (2-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen -2-em-3-carboxylic acid In the same manner as in Example 5-b), 11.9 milligrams of the header compound were obtained from 40.4 milligrams of (IS, 5R, 6S) -6- ((IR) - 1- - - hydroxyethyl) -l-methyl-2- (2-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D20) d (H0D = 4.80 ppm): 1.06 (3H, d, J = 7.1Hz), 1.32 (3H, d, J = 6.4Hz), 2.42 (3H, s), 3.62 (2H, m ), 4.31 (1H, m), 4.46 (1H, dd, Jl = 9.9Hz, J2 = 2.8Hz), 7., 52 (ÍH, s), 8.98 (ÍH, s).

Example 22 Acid (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (2-methylimidazo) [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylic acid __ a) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (2 -methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), 123 milligrams of ( 5R, 6S) -6- ((IR) -1-hydroxyethyl-2- (2-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate from 4- nitrobenzyl from 270 milligrams of (3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 406 milligrams of 2-methyl- 3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole, nuclear magnetic resonance (CDCI3) d: 1.37 (3H, d, J = 6.2), 2.18 (3H, s), 3.27 (2H, s) broad), 3.44 (ÍH, dd, Jl = 5.7Hz, J2 = 2.5Hz), 4.31 (1H, m), 4.51 (ÍH, m), 5.15 (111, d, - J = 13.4, 5.30 (1H, d, J = 13.4Hz), 6.99 (1H, kks), 7.33 (2Hi, d, J = 8.7), 7.78 (1H, s), 8.11 (2H, d, J = 8.7 Hz). b) Acid (5R, 6S) -6- ((IR) -l-hydroxyethyl-2- (2-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3 carboxylic In the same manner as in the Axis lo-b), 12.9 milligrams of the header count of 73 milligrams of (5R, 6S) -6- ((IR) -l-hydroxyethyl-2- (2-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl Nuclear magnetic resonance (D 0) d (HOD = 4.80 ppm): 1.30 (3H, d, J = 6.4Hz), 2.36 (3H, s), 3.14 (1H, dd, Jl = 17.7Hz, J2 = 10.1Hz), 3.38 (1H, dd, Jl = 17.7Hz, J2 = 8.6Hz), 3.61 (ÍH) , dd, Jl = 5.9Hz, J2 = 2.9Hz), 4.28 (1H, m), 4.42 (1H, m), 7.47 (1H, s), 8.80 (ÍH, s).

Example 23 (SS, 5R, 6S) -2- (7-chloro-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l- carbapen-2-em-3-carboxylate (internal salt) a) YES (5S, 5S) -2- (7-chloro-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6 iodide - ((IR) -1-hydroxyethyl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl _ - - In the same manner as in Example 4-a) with the exception that the reaction was carried out for 4 days, the iodide of (ΔS, 5R, 6S) -2- (7-chloro-6-methylimidazo [5, 1-b] thiazolium-2-yl-6- ((IR) -1-hydroxyethyl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl from 49 milligrams of (SS, 5R, 6S) -2- (7-chloroimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -1-methyl-1-carbapen-2- 4-nitrobenzyl em-3-carboxylate Nuclear magnetic resonance (DMSO-dg) d: 1.18 (3H, d, J = 6.2Hz), 1.22 (3H, d, J = 7.4Hz), 3.50 (1H, dd, J2 = 2.8Hz), 3.25 (1H, m), 4.01 (3H, s), 4.03 (1H, m), 4.40 (1H, dd, J? = 10.3Hz, J2 = 2.8Hz), 5.41 (ÍH, d , J = 13.9Hz), 5.53 (ÍH, d, J = 13.9Hz), 7.74 (2H, d, J = 8.9Hz), 8.24 (2H, d, J = 8.9Hz), 8.71 (1H, s), 9.69 (1H, s). B) (SS, 5R, 6S) -2- (7-chloro-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1 -hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate (internal salt) In the same manner as in Example 4-b), 12.1 milligrams of the compound of the heading from the whole amount of the iodide of (ΔS, 5R, 6S) -2- (7-chloro-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) 1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl previously obtained. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.24 (3H, d, J = 7.1Hz), 1.31 (3H, d, J = 6.4Hz), 3.54 (1H, dd, Jl = 6.1Hz, J2 = 2.9Hz), 3.63 (HH,), 4.01 (3H, s), 4.27 (HH, m), 4.32 (1H, dd, Jl = 9.4Hz, J2 = 2.9Hz), 8.11 (1H, s), 9.26 (1H, s).

Example 24 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of pivaloyloxymethyl in the same manner as in Example 19, the header compound was obtained from 30.6 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, lb] thiazole) acid -2-yl) -l-carbapen-2-em-3-carboxylic acid.

Nuclear magnetic resonance (CDCI3) d: 1.23 (9H, s), 1. 37 (3H, d, J = 6.2Hz), 3.30 (3H, m), 4.30 (2H,), 5.91 (1H, d, J = 5.5Hz), 6.01 (1H, d, J = 5.5Hz), 7.07 (1H, s), 8.05 (1H, s), 8.31 (ÍH, s).

Example 25 Acid (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-methylimidazo) [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylic acid a) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5- methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), 218 milligrams of (5R) were obtained , 6S) -6- ((IR) -1-hydroxyethyl-2- (5-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl from 730 milligrams of (3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 730 milligrams of 5-methyl-2 - (tri-n-butylstannyl) imidazo [5, 1-b] thiazole, nuclear magnetic resonance (CDCI3) d: 1.40 (3H, d, J = 6.4Hz), 2.59 (3H, s), 3.32 (3H, m ), 4.32 (2H, m), 5.31 (1H, d, J = 13.8Hz), 5.56 (1H, d, J = 13.8Hz, 6.91 (1H, s), 7.70 (2H, d, J = 8.9Hz) , 8.11 (1H, s), 8.25 (2H, d, J = 8.9Hz) b) Acid (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylic acid In the same manner as in Example 5-b), 46.5 milligrams were obtained of the header compound from 161 milligrams of (5R, 6S) -6- (IR) -1-hydroxyethyl) -2- (5-methylimidazo [5, 1-b] thiazol-2-yl) -l- carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1.30 (3H, d, J = 6.4Hz), 2.72 (3H, s), 3.23 (2H, m), 3.50 (1H, dd, J? = 5.8 Hz, J2 = 3.0Hz), 4.24 (2H, m), 7.23 (ÍH, s), 7.72 (ÍH, s).

Example 26 - (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate from pivaloyloxymethyl In the same manner as in Example 19, 20.0 milligrams of the header compound were obtained from 40.2 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-methylimidazo) acid [5, 1-b] thiazol-2-yl) -1-carbapen-2-em-3-carboxylic acid. Nuclear Magnetic Resonance (CDCI3) d: 1.23 (9H, s), 1.36J3H, d, J = 6.2Hz), 2.61 (3H, s), 3.26 (1H, dd, Jl = 6.6Hz, J2 = 2.8Hz), 3.33 (3H, m), 4.30 (2H, m), 5.90 (ÍH, d, J = 5.5Hz), 6.01 (1H, d, J = 5.5Hz), 6.91 (1H, s), 8.12 (1H, s ).

Example 27 (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2- sodium a-3-carboxylate a) (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazole-2- il) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), 110 milligrams of (1S, 5R, 6S) -6- ((IR) were prepared -1-Hydroxyethyl-l-methyl-2- (7-methylimidazo [5, 1-b] thiazol-2-yl) -1-carbapen-2-em-3-carboxylate of 4-nitrobenzyl as a yellow solid from of 725 milligrams of - (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2-oxo-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and 1.04 grams of -methyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear Magnetic Resonance (CDCI3) d: 1.30 (3H, d, J = 7.2Hz), 1.40 (3H, d, J = 6.2Hz), 2.34 (3H, s), 3.34-3.49 (2H,), 4.28-4.39 (2H, m), 5.27 (1H, d, J = 13.7Hz), 5.52 (1H, d, J = 13.7Hz), 7.67 (2H, d, J = 6.9Hz), 7.95 (1H, s), 8.23 (2H, d, J = 6.9Hz), 8.24 (ÍH, s). MS (TSP): 483 (M + + H). b) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen- Sodium 2-em-3-carboxylate _ 1.5 milligrams of the headed compound was obtained in the same manner as in Example 134-d) which will be described below with the exception that the reaction was carried out with 90 milligrams of ( 1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em 3-Nitrobenzyl carboxylate, and purification was carried out with CHP-20P (3 percent THF in water). Nuclear Magnetic Resonance (D20) d (HOD) 4.80 ppm): 1.24 (3H, d, J = 7.1Hz), 1.31 (3H, d, J = 6.3Hz), 2.34 (3H, s), 3.48-3.59 (2H , m), 4.21-4.32 (2H, m), 7.78 (1H, s), 8.01 (1H, S). MS (FAB +): 392 (M + + Na), 370 M + + H).

Example 28 (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (7-methylimidazo) [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of pivaloyloxymethyl. In the same manner as in Example 135 which will be described below, 28 milligrams of the compound were obtained of the heading from 42.8 milligrams of (SS, 5R, 6S) -6- ((IR-1-hydroxyethyl) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate sodium Nuclear magnetic resonance (CDCI3) d: 1.21 (9H, s), 1.29 (3H, d, J = 7.4Hz), 1.37 (3H, d, J = 6.2 Hz), 2.34 (3H, s), 3.32 (1H, dd, J! = 7.0Hz, J2 = 2.9Hz), 3.40-3.48 (lH, m), 4.25-4.35 (2H, m), 5.88 (1H, d, J = 5.6Hz), 5.99 (1H, d, J = 5.6Hz), 7.96 (1H, s), 8.25 (1H, s), MS (TSP: 462 (M + + H).

Example 29 (1S, 5R, 6S) -2- (6,7-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- 2-em-3-carboxylate (internal salt) a) Iodide of (S, 5R, 6S) -2- (6,7-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR ) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl - - In the same manner as in Example 4-a), 18.8 milligrams of (I S, 5R, 6S) -2- (6,7-dimethylimidazo [5, 1-b] thiazolium-2-yl) iodide were obtained. 6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl as a yellowish orange oil using 18.5 milligrams of (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and 0.5 milliliter of methyl iodide. Nuclear magnetic resonance (Acetone-dg) d: 1.31 (3H, d, J = 6.3Hz), 1.36 (3H, d, J = 7.2Hz), 2.63 (3H, s), 3.55 (1H, dd, J! = 6.3Hz, J2 = 3.0Hz), 3.82-3.92 (ÍH,), 4.22 (3H, s), 4.35-4.45 (ÍH, broad), 4.55 (ÍH, dd, J? = 9.9Hz, J2 = 3.0Hz ), 5.44 (1H, d, J = 13.8Hz), 5.62 (1H, d, J = 13.8Hz), 7.83 (2H, d, J = 6.9Hz), 8, 25 (2H, d, J = 6.9Hz) ), 9.01 (ÍH, s), 9.85 (1H, s). MS (TSI): 497 (M +). b) (1S, 5R, 6S) -2- (6,7-dimethylimidazo [5, 1-b] thiazolium-2-yl-6- ((1R-1-hydroxyethyl) -l-methyl-1-carbapen- 2-em-3-carboxylate (inner salt) In the same manner as in Example 4-b) except that 18.8 milligrams of (SS, 5R, 6S) -2- (6,7-dimethylimidazo [5] iodide were used. , 1-b] thiazolium-2-) -6- ((1R-1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and the purification carried out in CHP-20P (2 percent THF in water), 9.3 milligrams were obtained - - of the header compound as a yellow amorphous product. Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1. 25 (3H, d, J = 7.1Hz), 1.31 (3H, d, 6.3Hz), 2.41 (3H, s), 3. 53-3.65 (2H, m), 3.93 (3H, s), 4.22-4.36 (2H, m), 8.01 (1H, s), 9.05 (0.5H, s, partially exchanged with D20). MS (FAB +): 3.62 (M + + H).

Example 30 (5R, 6S-dimethylimidazo [5, lb] thiazolium-2-yl) -6- ((1R) -1-hydroxyethyl-1-carbapen-2-em-3-carboxylate (internal salt) a) (5R) iodide , 6S) -2- (5, 6-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-Nitrobenzyl In the same manner as in Example 4-a) with the exception that the reaction was carried out for 3 days, iodide of (5R, 6S) -2- (5,6-di-ethylimidazo) was obtained. [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl from 57 milligrams of the acid (5R , 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylic acid of 4- nitrobenzyl. Nuclear Magnetic Resonance (DMSO-dg) d: 1.17 (3H, d, J = 6.2Hz), 2.82 (3H, s), 3.48 (2H, m), 3.59 (1H, dd, J? = 5.5Hz, - J2) 3.1Hz), 3.92 (3H, s), 4.04 (1H, m), 4.33 (1H, m), 5.44 (1H, d, J = 13.7Hz), 5.55 (1H, d, J = 13.7Hz) , 7.71 (1H, s), 7.76 (2H, d, J = 8.8Hz), 8.25 (2H, d, J = 8.8Hz), 8.58 (ÍH, s). b) (5R, 6S) -2- (5,6-dimethylimidazo [5, 1-b] thiazolium-2-yl-6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 -carboxylate (inner salt) In the same manner as in Example 4-b), 14.2 milligrams of the header compound were obtained from the whole amount of (5R, 6S) -2- (5,6-dimethylimidazo) iodide [5, 1-b] thiazolium-2-yl) -6- ((IR-1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl obtained above, nuclear magnetic resonance ( D20) d (HOD = 4.80 ppm): 1.31 (3H, d, J = 6.4Hz), 2.77 (3H, s), 3.32 (2H, m), 3.55 (1H, dd, Jl = 6.2Hz, J2 = 3.0 Hz), 3.91 (3H, s), 4.28 (2H, m), 7.37 (ÍH, s), 7.83 (1H, s).

Example 31 Acid (IS, 5R, 6S) -2- (5-formylaminomethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen -2-ene-3- carboxylic acid a) (1S, 5R, 6S) -2- (5-formylaminomethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl - - In the same manner as in Example 5-a), 40.4 milligrams of (SS, 5R, 6S) -2- (5-formylaminomethylimidazo [5, lb] thiazol-2-yl) -6- ((IR) were obtained. 4-Nitrobenzyl-1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate from 305 milligrams of (IR, 3R, 5R, 6S) -6- ((IR) -1- hydroxyethyl) -l-methyl-2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 473 milligrams of 5-formylaminomethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear magnetic resonance (CDCI3) d: 1.33 (3H, d, J = 7.2Hz), 1.38 (3H, d, J = 6.3Hz), 3.37 (ÍH, dd, J? = 6.1Hz, J2 = 2.8Hz), 3.57 (ÍH, m), 4.34 (2H, m), 4.73 (2H, d, J = 6.3Hz), 5.29 (1H, d, J = 13.7Hz), 5.53 (1H, d, J = 13.7Hz), 6.94 (ÍH, s), 6.96 (1H, broad s) 7.66 (2H, d, J = 8.8Hz), 8.21 (2H, d, J = 8.8Hz), 8.26 (1H, s), 8.33 (1H, s ). b) Acid (1S, 5R, 6S) -2- (5-formylaminomethylimidazo) [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -1-methyl-l-carbapen-2-em-3-carboxylic acid In the same manner as in Example 5 -b), 44.3 milligrams of the header compound were obtained from 160 milligrams of (SS, 5R, 6S) -2- (5-formylaminomethylimidazo [5, 1-b] thiazol-2-yl) -6- (( IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl - - Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.25 (3H, d, J = 7.2Hz), 1.31 (3H, d, J = 6.4Hz), 3.55 (1H, dd, Jl = 6.0Hz, J2 = 2.7Hz), 3.64 (HH, m), 4.27 (HH, m), 4.34 (1H, dd, J! = 9.3Hz, J2 = 2.7Hz), 4.92 (2H, d, J = 2.7Hz), 7.37 (ÍH, s), 8.07 (ÍH, s), 8.25 (1H, s).

Example 32 (ΔS, 5R, 6S) -2- (5-formylaminomethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen-2- pivaloyloxymethyl em-3-carboxylate In the same manner as in Example 19, 31.2 milligrams of the header compound were obtained from 34.7 milligrams of the acid (IS, 5R, 6S) -2- (5-formylamino-methylimidazo [5 , lb] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylic acid. Nuclear magnetic resonance (CDCI3) d: 1.19 (9H, s), 1.31 (3H, d, J = 7.3Hz), 1.35 (3H, d, J = 6.2Hz), 3.34 (IH, dd, Jl = 6.0Hz, J2 = 2.9Hz), 3.56 (1H, m), 4.32 (2H, m), 4.77 (2H,), 5.86 (1H, d, J = 5.6Hz), 5.97 (1H, d, J = 5.6Hz) 6.94 (1H, s), 7.08 (1H, broad s), 8.26 (1H, s), 8.28 (1H, s).

Example 33 - (SS, 5R, 6S) -2- (5-formylaminomethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l- carbapen-2-em-3-carboxylate (internal salt) a) (I S, 5R, 6S) -2- (5-formylaminomethyl-6-methylimidazo [5, lb] thiazolium-2-yl) -6- iodide ( (IR) -1-hydroxyethyl) -1-methyl-l-carbapen-2-em-3-carboxylate of 3-nitrobenzyl In the same manner as in Example 4-a), the iodide of (S, 5R) was obtained , 6S) -2- (5-formylaminomethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -1-methyl-1-carbapen-2- 4-Nitrobenzyl em-3-carboxylate from 50.4 milligrams of (SS, 5R, 6S) -2- (5-formylaminomethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) - 1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (DMSO-dg) d: 1.18 (3H, d, J = 6.1Hz), 1.26 (3H, d, J = 7.1Hz), 3.50 (1H, dd, J? = 5.2Hz, J2 = 3.0Hz ), 3.76 (1H, m), 4.05 (3H, s), 4.07 (1H, m), 4.41 (1H, dd, Jl = 10.0Hz, J2 = 3.0Hz), 4.88 (2H, m), 5.19 (ÍH) , d, J04.9HZ), 5.41 (HH, d, J = 13.8Hz), 5.52 (HH, d, J = 13.8Hz), 7.73 (2H, d, J = 8.9Hz), 7.79 (1H, s) , 8.14 (1H, s), 8.22 (2H, d, J = 8.64 (1H, s), 8.83 (1H, m) b) (SS, 5R, 6S) -2- (5-formylaminomethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -1-methyl-l-carbapen-2-em-3-carboxylate (internal salt) In the same way as in Example 4-b), 22.2 milligrams of the header compound were obtained from the whole amount of the iodide of (SS, 5R, 6S) -2- (5-formylaminomethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1.28 (3H, d, J = 7.2Hz), 1.31 (3H, d; J = 6.4Hz), 3.56 (1H, m), 3.67 (1H, m ). 4.05 (3H, s), 4.28 (1H, m), 4.34 (1H, m), 4.95 (2H, d, J = 3.8Hz), 7.50 (1H, s), 8.16 (1H, s), 8.20 (1H , s).

Example 34 Acid (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl-1- (5-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-1-carbapen-2 em-3-carboxylic a) (1S, 5R, 6S) -2- (5-t-butyldimethylsilyloxymethylimidazo [5, 1-b] thiazole-2-) -6- ((IR) -1-hydroxyethyl) -l- methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), 799 milligrams of (1S, 5R, 6S) -2- (5-t- butyldimethylsilyloxymethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate - of 4-nitrobenzyl from 724 milligrams of (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2-oxo-l-carbapenam-3-carboxylate 4- Nitrobenzyl and 1.34 grams of 5- (t-butyldimethylsilyloxy) methyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear Magnetic Resonance (CDCI3) d: 0.08 (3H, s), 0.09 (3H, s), 0.89 (9H, s), 1.31 (3H, d, J = 7.4Hz), 1.40 (3H, d, J = 6.3 Hz), 3.36 (1H, dd, J? = 6.6Hz, J2 = 2.7Hz), 3.49 (1H,), 4.34 (2H, m), 4.97 (2H, s), 5.26 (1H, d, J = 13.7 Hz), 5.51 (1H, d, J = 13.7Hz), 6.94 (1H, s), 7.67 (2H, d, J = 8.8Hz), 8.23 (2H, d, J = 8.8Hz), 8.35 (1H, s). b) (SS, 5R, 6S) -6- ((IR) -1-bldroxyethyl) -2- (5-hydroxymethylimidazo [5, 1-b] thiazol-2-yl-l-methyl-l-carbapen-2 4-Nitrobenzyl-ene-3-carboxylate. To a solution of 799 milligrams of (SS, 5R, 6S) -2- (5-tt-butyldimethylsilyloxymethylimidazo [5, 1-b] thiazol-2-yl) - 6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 20 milliliters of THF were added 1.1 milliliter of acetic acid and 6.5 milliliters of a solution 1 M of tetra-n-butylammonium fluoride in THF under an argon atmosphere, and the mixture was stirred at room temperature for 30 minutes.The reaction mixture was concentrated under reduced pressure, and diluted with 100 milliliters of ethyl acetate. , 100 milliliters of an aqueous saline solution and a carbonate solution of - - saturated aqueous sodium hydrogen to adjust the pH to 7. 8. The organic layer was separated, washed with an aqueous saline solution and dried through anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue obtained in this way was purified by column chromatography on Sephadex LH-20 (chloroform: methanol) 1: 1) to provide 619 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (DMSO-dg)) d: 1.19 (3H, d, J = 6.3Hz), 2.23 (3, d, J = 7.2Hz), 3.40 (ÍH, dd, J? = 5.8Hz, J2 = 2.7 Hz), 3.69 (1H, m), 4.04 (1H, m), 4.33 (1H, dd, Ji = 9.7Hz, J2 = 2.8Hz), 4.68 (2H, d, J = 5.8Hz), 5.14 (1H, d, J = 5.2Hz), 5.38 (1H, d, J = 14.3Hz), 5.49 (1H, t, J = 5.8Hz), 5.51 (1H, d, J = 14.3Hz), 6.92 (1H, s) , 7.73 (2H, d, J = 8.5Hz), 8.21 (2H, d, J = 8.5), 8.36 (1H, s) c) Acid (SS, 5R, 6S) -6- ((IR) -1- hydroxyethyl) -2- (5-hydroxymethyl idazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylic acid In the same manner as in Example 5-b ), 57.8 milligrams of the header compound was obtained from 200 milligrams of (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-hydroxymethylimidazo [5, 1-b] thiazole) -2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl.

- - Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1.26 (3H, d, J = 7.6Hz), 1.32 (3H, d, J = 6.1Hz), 3.54 (1H, m), 3.63 (1H, m ), 4.30 (2H, m), 4.97 (2H, m), 7.18 (1H, s), 7.98 (1H, S).

Example 35 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2- pivaloyloxymethyl em-3-carboxylate In the same manner as in Example 19, 20.3 milligrams of the header compound were obtained from 39.6 milligrams of the acid (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl ) -2- (5-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylic acid. Nuclear Magnetic Resonance (CDCI3) d: 1.18 (9H, s), 1.28 (3H, d; J = 7.4Hz), 1.36 (3H, d, J = 6.3Hz), 3.33 (HI, dd, J! = 6.5Hz , J2 = 2.7Hz), 3.47 (1H, m), 4.31 (2H, m), 4.95 (2H, s), 5.87 (1H, d, J = 5.6Hz), 5.97 (1H, d, J = 5.6Hz ), 6.96 (1H, s), 8.26. { 1H, s).

Example 36 - - Acid (SS, 5R, 6S) -6- ((1R-1-hydroxyethyl) -2- (3-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-1-carbapen-2 em-3-carboxylic a) (1S, 5R, 6S) -2- (3-t-butyldimethylsilyloxymethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l -methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), 146 milligrams of (1S, 5R, 6S) -2- (3-t) were obtained -butyldimethylsilyloxymethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylic acid 4-nitrobenzyl ester from 256 milligrams of (IR, 3R, 5R, 6S) -6- ((IR) -l-hydroxyethyl-l-methyl-2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 346 milligrams of 3- ( t-butyldimethylsilyloxy) methyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole, nuclear magnetic resonance (CDCI3) d: 0.01 (3H, s), 0.06 (3H, s), 0.85 (9H , s), 1-22 (3H, d, J = 7.4Hz), 1.39 (3H, d, J = 6.2Hz), 3.40 (1H, m), 4.34 (1H, m), 4.44 (1H, m) , 4.45 (1H, d, J = 13.4Hz, 4.59 (1H, d, J = 13.4Hz), 5.19 (1H, d, J = 1 3.7 Hz), 5.40 (1H, d, J = 13.7Hz), 7.08 (1H, s), 7.52 (2H, d, J = 8.9Hz), 8.09 (1H, s), 8.15 (2H, d, J = 8.9Hz) b) (ÍS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (3-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-1 -carbapen-2-em-3-carboxylate of 4-nitrobenzyl - In the same manner as in Example 34-b), 75.9 milligrams of (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (3-hydroxymethylimidazo [5, 1-b] were obtained. ] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl from 200 milligrams of (IS, 5R, 6S) -2- (3-t-butyl- dimethylsilyloxymethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (CDCI3) d: 1.16 (3H, d, J = 7.4Hz), 1.37 (3H, d, J = 6.3Hz), 3.42 (2H, m), 4.32 (1H, m), 4.46 (1H, dd, J? = 10.4Hz, J2 = 3.1Hz), 4.54 (1H, d, J = 13.6Hz), 4.61 (1H, d, J = 13.5Hz), 5.22 (HI, d, J = 13.4Hz), 544 (ÍH, d, J = 13.4Hz), 7.07 (1H, s), 7.56 (2H, d, J = 8.5Hz), 8.18 (2H, d, J = 8.5Hz), 8.20 (ÍH, s). - c) Acid (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (3-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-l- carbapen-2-em-3-carboxylic acid. In the same manner as in Example 5-b), 11.4 milligrams of the header compound were obtained from 5.9 milligrams of (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- ( 3-Hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylic acid 4-nitrobenzyl ester. Nuclear Magnetic Resonance (D20)) d (HOD = 4.80 ppm): 1.18 (3H, d, J = 6.9Hz), 1.32 (3H, d, J = 6.4Hz, 3.44 (1H, m), - - 3. 61 (1H, m), 4.30 (1H, m), 4.42 (1H, m), 7.61 (1H, s), 9.19 (1H, s).

Example 37 Acid (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2 -em-3-carboxylic acid a) (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazol-3-yl ) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl The same as in Example 5-a), 406 milligrams of (IS, 5R, 6S) -6- ((IR) -1 were obtained -hydroxyethyl) -1-methyl-2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl from 543 milligrams of ( IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 780 milligrams of 7-methyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear magnetic resonance (CDCI3) d: 1.16 (3H, d, J = 7.4Hz), 1.37 (3H, d, J = 6.3Hz), 2.29 (3H, s), 3.46 (1H, dd, J! = 6.0Hz , J2 = 3.2Hz), 3.63 (HH, m), 4.33 (HH, m), 4.51 (HH, dd, J1 = 10.4Hz, J2 = 3.2Hz), 5.13 (HH, d, J = 13.4Hz), 5.31 (1H, d, J = 13.4Hz), 6.92 (1H, s), 7.36 (2H, d, J = 8.5Hz), 7.75 (1H, s), 8.14 (2H, d, J = 8.5Hz). b) Acid (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -1-methyl-2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen -2-em-3-carboxylic acid In the same manner as in Example 5-b), 79.1 milligrams of the header compound were obtained from 200 milligrams of (1S, 5R, 6S) -6- ((IR) - 1-hydroxyethyl) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylic acid 4-nitrobenzyl ester. Nuclear magnetic resonance (D20) d: (HOD = 4.80 ppm): 1.14 (3H, d, J = 7.4Hz), 1.31 (3H, d, J = 6.4Hz), 2.42 (3H, s), 3.55 (ÍH, m), 3.60 (HH, dd, J? = 5.9Hz, J2 = 3.0Hz), 4.30 (HH, m), 4.42 (1H, dd, Jl = 10.0Hz, J2 = 3.0Hz), 7.37 (1H, s ), 8.60 (1H, s).

Example 38 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate from sodium a) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3 4-Nitrobenzylcarboxylate In the same manner as in Example 5-a), 758 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methylimidazo [5] were obtained. , 1-b] thiazol-2-yl) -1-carbapen-2-em-3-carboxylate of 4-nitrobenzyl as an amorphous orange compound from 934 milligrams of (3R, 5R, 6S) -6- (( IR) -1-hydroxyethyl) -2-oxo-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and 1.375 grams of 7-methyl-2- (tri-n-butylstannyl) imidazo [5, 1- b] thiazole. Nuclear magnetic resonance (CDCI3) d: 1.40 (3H, d, J = 6.3Hz), 2.1 (1H, broad s), 2.33 (3H, s), 3.29-3.36 (3H, m), 4.25-4.38 (2H, m), 5.31 (1H, d, J = 13.7Hz), 5.54 (1H, d, J = 13.7Hz), 7.69 (2H, d, J = 6.9Hz) 7.93 (1H, s), 8.14 (1H, s ), 8.24 (2H, d, J = 6.9Hz). MS (TSP): 469 (M + + H) b) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methylimidazo [5, 1-b] thiazol-2-yl) sodium l-carbapen-2-em-3-carboxylate In the same manner as in Example 134-d) which will be described below except that 328 milligrams of (5R, 6S) -6- ((R-) 1-hydroxyethyl) -2- (7-methyloxyzo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and the purification was carried out with CHP -24P (2 percent THF in water), and 111.4 milligrams of the header compound were obtained Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.30 (3H, d, J = 6.3Hz), 2.37 ( 3H, s), 3.31-3.34 (2H, broad s, t), 3.53-355 (lH, m), 4.22- .35 (2H, m), 7.82 (1H, s), 8.70 (1H, s). MS (TSP): 356 (M + + Na), 334 (M + + H).

Example 39 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-m-3-carboxylate from pivaloyloxymethyl .. __ In the same manner as in Example 135 described below, 29.1 milligrams of the header compound was obtained as a yellow powder of 51.4 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-Methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylic acid sodium. Nuclear Magnetic Resonance (CDCI3) d: 1.22 (9H, s), 2.33 (3H, s), 3.22-3.34 (3H, m), 4.24-4.35 (2H, m), 5.90 (1H, d, J = 5.6Hz ), 6.00 (1H, d, J5.6Hz), 7.94 (1H, s), 8.18 (1H, s). MS (TSP): 4.48 (M + + H).

Example 40 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2- Pivaloylmethyl em-3-carboxylate In the same manner as in Example 19, 28.3 milligrams of the header compound was obtained from 39.5 milligrams of (1S, 5R, 6S) -6- ((IR) -1-hydrostyl-5-hydroxy acid ) -l-methyl-2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylic acid.

- - Nuclear Magnetic Resonance (CDCI3) d: 1.12 (3H, d, J = 7.2Hz), 1.16 (9H, s), 1.36 (3H, d, J = 6.2Hz), 2.34 (3H, s), 3.41 (ÍH, dd, J! = 6.5Hz, J2 = 3.2Hz), 3.70 (HH, m), 4.31 (HH, m), 4.47 (HH, dd, 5.73 (1H, d, J = 5.5Hz), 5.86 (1H, d, J = 5.5Hz), 7.03 (1H, s), 7.78 (1H, s).

Example 41 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-hydroxymethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -l-methyl-l- carbapen-2-em-3-carboxylate (internal salt) In the same manner as in Example 14, with the exception that the reaction was carried out for 3 days, 19.3 milligrams of the header compound were obtained from 100 milligrams of (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -l-methyl-1-carbapen- 4-Nitrobenzyl 2-em-3-carboxylate. Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1.26 (3H, d, J = 6.9Hz), 1.32 (3H, d, J = 6.1Hz), 3.56 (1H, m), 3. 66 (1H, m), 4.05 (3H, s), 4.30 (2H, m), 5.13 (2H, s), 7. 5K1H, S), 8.14 (ÍH, s).

Example 42 - (5R, 6S) -2- (6,7-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3- carboxylate (internal salt) a) (5R, 6S) -2- (6,7-Dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l iodide -carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 4-a), 64.0 milligrams of (5R, 6S) -2- (6, 7-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) iodide were prepared 4-nitrobenzyl carbapen-2-em-3-carboxylate as a yellow-orange oil using 93.7 milligrams of (5R, 6S) -6- ((1R-1-hydroxyethyl) -2- (7-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl, nuclear magnetic resonance (CD3OD) d: 1.31 (3H, d, J = 6.3Hz), 2.49 (3H , s), 3.45-3.55 (3H, m), 4.01 (3H, s), 4.10-4.25 (1H, m), 4.30-4.40 (ÍH, m), 5.40 (1H, d, J = 13.5Hz), 5.55 (1H, d, J = 13.3Hz), 7.76 (2H, d, J = 9Hz), 8.24 (2H, d, J = 9.0Hz), 8.38 (ÍH, s), 9.35 (0.2H, s, exchange with CD3OD) MS (TSP); 483 (M +). b) (5R, 6S) -2- (6,7-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em- 3-carboxylate (internal salt) The compound of the heading was obtained in a yield of 7.2 milligrams as an amorphous compound - - yellow from 61.0 milligrams of (5R, 6S) -2- (6,7-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl-1-carbapen- 2-em-3-carboxylate of 4-nitrobenzyl in the same manner as in Example 4-b) with the exception that the purification was carried out in CHP-20P (2 percent THF in water) and COSMOSEAL 40C18 -PREP (water: methanol = 20: 1 - 10: 1). Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1.30 (3H, d, J = 6.3Hz), 2.41 (3H, s), 3.24-3.40 (2H, m), 3.51-3.55. { 1H, m), 3.92 (3H, s), 4.22-4.28 (2H, m), 7.86 (1H, m), 9.04 (0.5H, s, exchanged with D20). MS ().

Example 43 Acid (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-3-em-3-carboxylic acid a) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7- methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), 608 milligrams of (5R) were obtained , 6S) -6- ((IR-l-hydroxyethyl) -2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl from 696 milligrams of (3R, 5R, 6S) -6- ((1 (IR) -1-hydroxyethyl) -2-oxo-l-carbapenam-3- - - 2-nitrobenzyl carboxylate and 1.05 grams of 7-methyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear Magnetic Resonance (CDCI3) d: 1.39 (3H, d, J = 6.3Hz), 2.30 (3H, s), 3.35 (3H, m), 4.31 (1H, m), 4.43 (1H, m), 5.21 ( HH, d, J = 13.3Hz), 5.34 (HH, d, J = 13.3Hz), 7.01 (HH, s), 7.42 (2H, d, J = 8.9Hz), 7.67 (1H, s), 8.16 ( 2H, d, J = 8.9Hz). b) Acid (5R, 6S) -6- ((1R-1-hydroxyethyl) -2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3 carboxylic acid In the same manner as in Example 5-b), the header compound was obtained in a yield of 45.5 milligrams from 306 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) - 2- (7-Methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.32 (3H, d, J = 6.1Hz), 2.48 (3H, s), 3.25 (1H, dd, J? = 17.2Hz, J2-10.0Hz) , 3.47 (1H, dd, J! = 17.2Hz, J2 = 8.4Hz), 3.61 (1H, m), 4.29 (1H, m), 4.40 (1H, m), 7.47 (1H, s), 8.73 (1H , s).

Example 44 (5R, S) -6- ((IR) -l-hydroxyethyl-2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of pivaloyloxymethyl In the same manner as in Example 19, the header compound was obtained in a yield of 37.8 milligrams from 62.6 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- ( 7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-carboxylic acid, nuclear magnetic resonance (CDCI3) d: 1.19 (9H, s), 1.38 (3H, d, J = 6.2Hz), 2.34 (3H, s), 3.35 (3H, m), 4.28 (1H, m), 4.40 (1H, m), 5.78 (1H, d, J = 5.5Hz), 5.88 (1H, d, J = 5.5Hz), 7.09 (1H, s), 7.71 (1H, s).

Example 45 (5R, 6S) -2- (6,7-dimethylimidazo [5, 1-b] thiazolium-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em -3- carboxylate (internal salt) a) (5R, 6S) -2- (6, 7-dimethylimidazo [5, 1-b] thiazolium-3-yl) -6- ((IR) -1-hydroxyethyl) -l iodide 4-nitrobenzylcarbapen-2-em-carboxylate In the same manner as in Example 4-a), (5R, 6S) -2- (6,7-dimethylimidazo [5, 1-b] iodide was obtained ] thiazolium-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl from 103 milligrams of (5R, 6S) -6- ( (IR) -1-hydroxyethyl) -2- (7-methylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylic acid 4-nitrobenzyl ester.

Nuclear Magnetic Resonance (DMSO-dg) d: 1.18 (3H, d, J = 6.2Hz), 2.39 (3H, s), 3.30 (2H, m), 3.55 (1H, m), 3.88 (3H, s), 4.04 (1H, m), 4.33 (1H, m), 5.22 (1H, d, J = 13.7Hz), 5.31 (1H, d, J = 13.7Hz), 7.53 (2H, d, J = 8.7Hz), 7.84 (1H, s), 8.20 (2H, d, J = 8.7Hz), 9.57 (1H, .s). b) (5R, 6S) -2- (6,7-dimethylimidazo [5, lb] thiazolium-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3- carboxylate (internal salt) In the same way as in Example 4-b), the compound of the heading was obtained in a yield of 24.9 milligrams from the whole amount of the iodide of (5R, 6S) -2- (6,7-dimethylimidazo [5, 1-b] thiazolium-3-yl) -6- ((1R) -1-hydroxyethyl) -l-carbapen-2-em-3 4-nitrobenzyl carboxylate obtained above. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.30 (3H, d, J = 6.5Hz), 2.45 (3H, s), 3.22 (1H, dd, J? = 17.6Hz, J2 = 10.2Hz) , 3.44 (ÍH, dd, J! = 17.6Hz, J2 = 8.8Hz), 3.58 (1H, dd, Jl = 5.8Hz, J2 = 2.8Hz), 3.94 (3H, s), 4.26 (1H, m), 4.37 (1H, m), 7.44 (H, s), 8.85 (H, s).

Example 46 Acid (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (3-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylic acid a) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (3-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3 4-Nitrobenzyl carboxylate In the same manner as in Example 5-a), (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (3-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 622 grams from 696 milligrams of (3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 1.14 grams of 3-methyl-2- (tri) -n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear magnetic resonance (CDCI3) d: 1.39 (3H, d, J = 6.3Hz), 2.20 (3H, s), 3.20 (2H, m), 3.35 (1H, dd, J2 = 2.9Hz), 4.31 (ÍH, m), 4.40 (1H, m), 5.24 (IH, d, J = 13.7Hz), 5.42 (1H, d, J = 13.7Hz), 7.09 (1H, s), 7.54 (2H, d, J = 8.4 Hz), 7.86 (1H, s), 8.15 (2H, d, J = 8.4Hz). b) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (3-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3 acid -carboxylic acid In the same manner as in Example 5-b), the header compound was obtained in a yield of 94. 6 milligrams from 329 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (3-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen- 4-Nitrobenzyl 2-em-3-carboxylate. Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1.30 (3H, d, J = 6.5Hz), 2.37 (3H, s), 3.15 (1H, dd, J? = 17.3Hz, - J2 = 10.2Hz), 3.32 (ÍH, dd, J? = 17.3Hz, J2 = 8.3Hz), 3.58 (1H, dd, Jl = 5.8Hz, J2 = 3.0Hz), 4.26 (1H, m), 4.37 ( ÍH, m), 7.52 (ÍH, s), 9.06 (1H, s).

Example 47 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (3-methylimidazo [5, 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate from pivaloyloxymethyl In the same manner as in Example 19, 38.6 milligrams of the header compound of 61.4 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (3-methylimidazo [5]) were obtained. , 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylic acid. Nuclear Magnetic Resonance (CDCI3) d: 1.11 (9H, s), 1.37 (3H, d, J = 6.3Hz), 2.30 (3H, s), 3.19 (2H, m), 3.31 (1H, dd, J? = 6.5Hz, J2 = 2.9Hz), 4.28 (1H, m), 4.36 (1H, m), 5.80 (1H, d, J = 5.5Hz), 5.90 (1H, d, J = 5.5Hz), 7.08 (1H , s), 7.93 (1H, s).

Example 48 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -l-methyl-l-carbapen-2-em- Potassium 3-carboxylate - a) (3S, 4R) -1- [(allyloxycarbonyl) (triphenylphosphoranilidene) methyl] -3- ((IR) -1-t- __-butyldimethylsilyloxyethyl) -4- [(IR) -1- [(pyridin-2- il) thiocarbonyl] ethyl] azetidin-2-one To the ice-cooled mixture of 6.6 grams of (3S, 4R) -1- [(allyloxycarbonyl) (triphenylphosphoranylidene) methyl] -3- ((IR) -1-t-butyldimethylsilyloxyethyl) -4- [(IR) -1- (carboxy) ethyl] azetidin-2- One and 2.75 grams of triphenylphosphine in 30 milliliters of acetonitrile were added 2.31 grams of 2,2 '-dipyridyl disulfide under the argon atmosphere, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure and purified by column chromatography on silica gel (hexane: ethyl acetate = 3: 1) to provide 5.2 grams of (3S, 4R) -1- [(allyloxycarbonyl) (triphenylphosphoranilidene ) methyl] -3- ((IR) -1-t-butyldimethylsilyloxyethyl) -4- [(IR) -1 - [(pyridin-2-yl) thiocarbonyl] ethyl] azetidin-2-one. Nuclear Magnetic Resonance (CDCI3) d: -0.15 (3H, s), -0.07 (3H, s), 0.80 (9H, s), 0.97 (3H, d, J = 6.1Hz), 1.13 (3H, d, J = 7.1Hz), 2.25-2.35 (HH, m), 2.60-2.67 (2H, m), 3.16 (1H, m), 4.15-4.30 (HH, m), 4.60-4.75 (2H, m), 5.10- 5.22 (ÍH, m), 7.50-7.80 (19H, m).

- - Ali (1S, 5R, 6S) -6- ((1R) -lt-butyldimethylsilyloxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -1-methyl-1-carbapen-2-em -3-carboxylate To an ice-cooled solution of 0.61 grams of 5-bromoimidazo [5, 1-b] thiazole in 6 milliliters of THF was added 3.2 milliliters of a 1M solution of ethyl magnesium bromide in THF. After being stirred at room temperature for 2 hours, the mixture was cooled to -50 ° C and a solution of 2.23 grams of (3S) was added., 4R) -1- [(allyloxycarbonyl) (triphenylphosphoranilidene) methyl] -3- ((IR) -1-t-butyldimethylsilyloxyethyl) -4- [(IR) -1- [(pyridin-2-yl) thiocarbonyl] ethyl ] azetidin-2-one in 6 milliliters of THF. The mixture was stirred for 1 hour during which the temperature was raised to 10 ° C. The reaction mixture was diluted with 12 milliliters of a saturated aqueous solution of ammonium chloride, extracted with dichloromethane and the organic layer was dried through anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue thus obtained was purified by column chromatography on silica gel (hexane: ethyl acetate = 3: 2) to provide 0.67 gram of the crude product. A 0.63 gram portion of the crude product and a 4.5 milligram solution of hydroquinone in 7 milliliters of xylene were stirred under heating at 140 ° C for 6 hours. The reaction mixture was diluted with 30 milliliters of acetate - - of ethyl, washed with saturated aqueous sodium hydrogen carbonate and a saturated aqueous saline solution in this sequence and dried through anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue thus obtained was purified by column chromatography on silica gel (hexane: ethyl acetate = 2: 1) to provide 0.35 gram of allyl (1S, 5R, 6S) -6 - ((IR) -1-t-butyldimethylsilyloxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -methyl-l-carbapen-2-em-3-carboxylate. Nuclear Magnetic Resonance (CDCI3) d: 0.12 (6H, s), 0.90 (9H, s), 1.12 (3H, d, J = 7.4Hz), 1.29 (3H, d, J = 6.1Hz), 3.32 (1H, dd, J = 2.9, 6.4Hz), 3.81-3.91 (ÍH, m), 4.23- .35 (2H,), 4.62-4.78 (2H, m), 5.18-5.38 (2H, m), 5.79-5.93 ( ÍH,), 6.90 (1H, d, J = 4.2Hz), 7.17 (1H, d, J = 4.2Hz), 7.31 (1H, s). c) Allyl (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -l-methyl-l-carbapen-2 -em-3-carboxylate To a solution of 0.35 g of allyl (1S, 5R, 6S) -6- ((IR) -1-t-butyldimethylsilyloxyethyl) -2- (imidazo [5, 1-b] thiazole-5) -yl) -l-methyl-l-carbapen-2-em-3-carboxylate in 12 milliliters of THF was added under ice cooling 0.66 milliliter of acetic acid and 2.9 milliliters of a 1M solution of tetra-n fluoride. -butylammonium in THF and the mixture was stirred at room temperature for 36 hours. The reaction mixture was diluted with 50 milliliters of - ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and a saturated aqueous saline solution in this sequence was dried through anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue obtained in this way was purified by column chromatography on silica gel (ethyl acetate) to provide 0.16 gram of allyl (1S, 5R, 6S) -6- ((IR) - 1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -1-methyl-l-carbapen-2-em-3-carboxylate. Nuclear Magnetic Resonance (CDCI3) d: 1.17 (3H, d, J = 7.4Hz), 1.37 (3H, d, J = 6.3Hz), 3.38 (1H, dd, J = 2.9, 6.6Hz), 3.82-3.92 ( ÍH, m), 4.25-4.35 (ÍH, m), 4.39 (1H, dd, J = 2.9, 10.0Hz), 4.60-4.78 (ÍH, m), 5.18-5.34 (2H, m), 5.77-5.90 ( 1H,), 6.91 (1H, d, J = 4.3Hz), 7.15 (1H, d, J = 4.3Hz), 7.31 (1H, s). d) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -l-methyl-l-carbapen-2- potassium em-3-carboxylate To a solution of 40 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) Allyl-1-methyl-l-carbapen-2-em-3-carboxylate in 0.8 milliliter of dichloromethane and 0.8 milliliter of ethyl acetate were added, under the argon atmosphere, 3.4 milligrams of triphenylphosphine, 29 milligrams of 2- potassium ethylhexanoate, 6.4 milligrams of tetrakis- palladium - - triphenylphosphine (0), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was emptied into diethyl ether and the resulting precipitated material was collected by filtration and purified by column chromatography on COSMOSEAL 40C18-PREP (water: methanol = 20: 1) to provide 13 milligrams of the header compound. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.10 (3H, d, J = 7.2Hz), 1.31 (1H, d, J = 6.4Hz), 3.50-3.65 (2H, m), 4.25-4.37 (2H, m), 7.10 (1H, d, J = 4.3Hz), 7.22 (1H, s), 7.38 (ÍH, d, J = 4.3Hz).

Example 49 (SS, 5R, 6S) -2- (7-formylaminomethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l- carbapen-2-em-3-carboxylate (internal salt) To a solution of 134 milligrams of (1S, 5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 2 milliliters of DMF was added 1.6 milliliters of methyl iodide and the mixture was stirred at room temperature for 12 hours. The solvent was removed under reduced pressure. The residue obtained in this way was dissolved in 5 milliliters THF and 5 milliliters of a 0.1 M sodium phosphate stabilizer (pH of 6.8) and 150 milligrams of 10 percent Pd-C. The reactor was purged with hydrogen, the reaction mixture was stirred at room temperature for 1 hour. The catalyst was collected by filtration and washed with a mixed solution of 2 milliliters of a 0.1 M sodium phosphate stabilizer (pH of 6.8) and 2 milliliters of THF. The filtrate was washed with 10 milliliters of ethyl acetate and the obtained aqueous layer was purified by column chromatography on COSMOSEAL 40C18-PREP (water: methanol = 20: 1). The fraction containing the desired product was concentrated under reduced pressure and then lyophilized to provide 58 milligrams of the header compound. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.24 (3H, d, J = 7.2Hz), 1.30 (3H, d, J = 6.4Hz), 3.52-3.68 (2H, m), 4.01 (3H) , s), 4.23-4.35 (2H, m), 4.68 (2H, s), 8.09 (1H, s), 8.26 (1H, s), 9.15 (1H, s).

Example 50 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -1-methyl-l-carbapen-2-em- Pivaloyloxymethyl 3-carboxylate - - To a solution of 40 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -1-methyl-1 potassium carbonate-2-em-3-carboxylate in 0.8 milliliter of DMF, 30 milligrams of pivaloyloxymethyl iodide were added at -30 ° C and the mixture was stirred for 1 hour through which time the temperature was raised to the room temperature. The reaction mixture was diluted with 30 milliliters of dichloromethane, washed with a semi-saturated aqueous saline solution and dried through anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue obtained in this way was purified by column chromatography on silica gel (ethyl acetate: methanol = 4: 1) to provide 54 milligrams of the header compound. Nuclear magnetic resonance (CDCI3) d: 1.17 (3H, d, J = 7.0Hz), 1.20 (9H, s), 1.37 (3H, d, J = 6.3Hz), 3.38 (1H, dd, J = 2.9, 6.6 Hz), 3.85-3.95 (lH, m), 4.25-4.33 (ÍH, m), 4.38 (1H, dd, J = 2.9, 10.0Hz), 5.78 (1H, d, J = 5.5Hz), 5.96 (1H , d, J = 5.5Hz), 6.95 (1H, d, J = 4.2Hz), 7.15 (1H, d, J = 4.2Hz), 7.34 (ÍH, s).

Example 51 (5R, 6S) -2- (3,6-dimethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) 1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate (internal salt) - In the same manner as in Example 14, 4.6 milligrams of the header compound was obtained from 109 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (3-methylimidazo [5 , 1-b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.31 (3H, d, J = 6.5Hz), 2.36 (3H, s), 3.15 (1H, dd, J? = 17.1Hz, J2 = 9.8Hz) , 3.32 (ÍH, dd, J1 = 17.1Hz J2 = 8.3Hz), 3.59 (1H, m), 4.09 (3H, s), 4.28 (1H, m), 4.38 (1H, m), 7.57 (1H, s ), 9.20 (ÍH, s).

Example 52 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em- Acetoxymethyl 3-carboxylate To a solution of 49 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) - Sodium 1-methyl-l-carbapen-2-em-3-carboxylate in 1 milliliter of DMF was added 32 milligrams of acetoxymethyl bromide under an argon atmosphere at -20 ° C, and the mixture was stirred for 3 hours at through which period of time the temperature rose to -10 ° C. The reaction mixture was extracted twice with 20 milliliters of ethyl acetate and the organic layer was washed twice with 10 milliliters of a - - Aqueous semi-saturated saline solution, dried through anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to a volume of 2 milliliters. The residue obtained in this way was purified by silica gel column chromatography (chloroform: methanol = 9: 1) in Sephadex LH-20 (dichloromethane: methanol = 1.1) in this sequence to provide 11 milligrams of the header compound . Nuclear Magnetic Resonance (CDCI3) d: 1.29 (3H, d, J = 7.4Hz), 1.37 (3H, d, J = 6.3Hz), 2.13 (3H, s), 3.31-3.51 (2H, m), 4.27- 4.39 (2H, m), 5.88, 5.96 (2H, AB, J = 5.7Hz), 7.08 (1H, s), 8.06 (1H, s), 8.38 (1H, s). MS (TSP): 406 (M + + H).

Example 53 (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em- 3-carboxylate of 1- (acetoxy) ethyl (diastereomeric mixture) In the same manner as in Example 52, 11 milligrams of the header compound were obtained from 49 milligrams of (IS, 5R, 6S) -6- (( IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate sodium and 45 milligrams of iodide of 1 - (acetoxy) ethyl.

- Nuclear magnetic resonance (CDCI3) d: 1.27, 1.28 (total 3H, d of each, J = 7.1Hz), 1.37, 1.38 (3H total, of each, J = 6.0Hz), 1.56, 1.61 (3H total , d of each, J = 5.5Hz), 2.06, 2.13 (3H total, s of each), 3.09-3.49 (2H, m), 4.26-4.42 (2H, m), 7.01-7.07 (2H, m ), 8.05 (1H, s), 8.41 (ÍH, s).

Example 54 (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em- 3-carboxylic acid (1-methylcyclohexan-1-yl) carbonyloxymethyl ester In the same manner as in Example 52, 42 milligrams of the header compound were obtained from 49 milligrams of (SS, 5R, 6S) -6- (( IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate sodium and 39 milligrams of iodide of ( 1-methylcyclohexan-1-yl) carbonyloxymethyl. Nuclear Magnetic Resonance (CDCI3) d: 1.14 (3H, s), 1.28 (3H, d, J = 7.1Hz), 1.36 (3H, d, J = 6.1Hz), 1.17-1.60 (8H,), 1.95-2.05 (2H,), 3.29-3.50 (2H, m), 4.25-4.40 (2H, m), 5.92, 5.97 (2H, AB, J = 5.5Hz), 7.07 (1H, s), 8.07 (1H, s) , 8.33 (ÍH, s).

Example 55 (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2- 1- (ethoxycarbonyloxy) ethyl em-3-carboxylate (diastereomeric mixture) In the same manner as in Example 52, 39 milligrams of the header compound were obtained from 49 milligrams of (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylic acid sodium and 68 milligrams of iodide of 1- (ethoxycarbonyloxy) ethyl. Nuclear Magnetic Resonance (CDCI3) d: 1.27-1.29 (9Hm), 1.59, 1.65 (3H total, d of each, J = 5.5Hz), 3.30-3.49 (2H, m), 0 4.15-4.45 (4H, m ), 6.91-7.00 (ÍH, m), 7.07 (1H, s), 8.04 (1H, s), 8.41, 8.42 (1H total, s of each). MS (TSP): 450 (M + + H).

Example 56 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em- 3 1 - (isopropoxycarbonyloxy) ethyl 3-carboxylate (diastereomeric mixture) In the same manner as in Example 52, 30 milligrams of the header compound was obtained from 49 milligrams of (IS, 5R, 6S) -6- ( (IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l- - - sodium carbapen-2-em-3-carboxylate and 71 milligrams of 1- (isopropoxycarbonyloxy) ethyl iodide. Nuclear magnetic resonance (CDCI3) d: 1.26-1.39 (12H, m), 1. 59, 1.65 (3H total, d of each, J = 5.5Hz), 3.29-3.49 (2H, m), 4.26-4.35 (2H, m), 4.84-5.00 (ÍH, m), 6.91-6.98 (ÍH , m), 7. 07 (1H, m), 8.03 (1H, s), 8.43 (1H, s). MS (TSP): 464 (M + + H).

Example 57 (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em- 3- (cyclohexyloxycarbonyloxy) ethyl 3-carboxylate (diastereomeric mixture) In the same manner as in Example 52, 30 milligrams of the header compound was obtained from 49 milligrams of (IS, 5R, 6S) -6- (( IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate sodium and 62 milligrams of iodide of 1 - (cyclohexyloxycarbonyloxy) ethyl. Nuclear magnetic resonance (CDCI3) d: 1.28, 1.29 (total 3H, d of each, J = 7.4Hz), 1.36, 1.38 (3H total, d of each, J = 6.4Hz), 1.59, 1.65 (3H total , d of each, J = 5.4Hz), 1.15-2.05 (8H, m), 3.29-3.49 (2H,), 4.26-4.35 (2H, m), 4.57-4.75 (lH, m), 6.92-6.98 (1H, m), 7.07 (1H, s), 8.03 (ÍH, s), 8.43 (Total HI, s of each).

- - MS (TSP): 504 (M + + H).

Example 58 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em- Cyclohexyloxycarbonyloxymethyl 3-carboxylate In the same manner as in Example 52, 46 milligrams of the header compound were obtained from 49 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2 - (sodium imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate and 59 milligrams of cyclohexyloxycarbonyloxymethyl iodide. Nuclear Magnetic Resonance (CDCI3) d: 1.28 (3H, d, J = 7.4Hz), 1.37, (3H, d, J = 6.2Hz), 1.20-1.60 (4H, m), 1.68-1.80 (2H, M) , 1.82-1.98 (2H, m), 3.30-3.50 (2H, m), 4.25-4.40 (2H,), 4.61-4.70 (1H, m), 5.90, 5.96 (2H, AB, J = 5.8Hz), 7.08 (1H, s), 8.05 (1H, s), 8.41 (1H, s).

Example 59 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em- 3-phthalidyl 3-carboxylate (diastereomeric mixture) - In the same manner as in Example 52, 38 milligrams of the header compound was obtained from 44 milligrams of (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5 , 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate sodium and 32 milligrams of 3-phthalidyl bromide. Nuclear magnetic resonance (CDCI3) d: 1.25-1.40 (6H, m), 3.30-3.60 (2H, m), 4.21-4.35 (2H, m), 7.07, 7.10 (total 1H, s of each), 7.46, 7.47 (total HI, s of each), 7.62-7.86 (4H, m), 8.01, 8.06 (total HI, s of each), 8.25, 8.51 (1H total, s of each). MS (TSP): 466 (M + + H).

Example 60 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em- (5-Methyl-2-oxo-1,3-dioxolen-4-yl) methyl-3-carboxylate In the same manner as in Example 52, 37 milligrams of the header compound were obtained from 49 milligrams of (S) , 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3- sodium carboxylate and 53 milligrams of (5-methyl-2-oxo-l, 3-dioxolen-4-yl) methyl bromide.

Nuclear magnetic resonance (CDCI3) d: 1.29 (3H, d, J = 7.4Hz), 1.37 (1H, d, J = 6.3Hz), 2.22 (3H, s), 3.32-3.52 (2H, m), 4.25- 4.45 (2H, m), 5.01, 5.08 (2H, AB, J = 14.0Hz), 7.08 (1H, s), 8.07 (1H, s), 8.26 (1H, s).

Example 61 (1S, 5R, 6S) - 6- ((IR) -1-hydroxyeti 1) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2 -em-3-1- [(cyclohexylmethoxy) carbonyloxy] ethyl carboxylate (diastereomeric mixture) In the same manner as in Example 52, the header compound was obtained in a yield of 42.1 milligrams from 44.8 milligrams (1S) , 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3- sodium carboxylate and 89.9 milligrams of 1- [(cyclohexylmethoxy) carbonyloxy] ethyl iodide. Nuclear Magnetic Resonance (CDCI3) d: 0.85-1.00 (2H, m), 1.10-1.20 (2H, m), 1.20, 1.21 (3H total, d of each, J = 7.2Hz), 1.28, 1.31 (3H total , d of each, J = 6.2Hz), 1.53 (3H, d, J = 5.5Hz), 1.58 (3H, d, J = 5.5Hz), 1.60-1.75 (4H, m), 1.98-2.10 (4H , m), 3.25-3.28 (ÍH, m), 3.34-3.42 (1H, m), 3.88-3.96 (2H, m), 4.78-4.30 (2H, m), 6.83-6.90 (1H, m), 7.02 (1H, s), 8.02 (1H, s), 8.35-8.36 (ÍH, m).

- MS (TSP): 518 (M + + H) Example 62 (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, lb] thiazol-2-yl) -l-methyl-1-ca. Rbapen-2-em 3 - [(2-methylcyclohexane-1-11) oxycarbonyloxy] ethyl carboxylate (diastereomeric mixture) In the same manner as in Example 52, 59.6 milligrams of the header compound were obtained from 61.7 milligrams of ( ÍS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3 sodium carboxylate and 89.0 milligrams of 1 [(2-methylcyclohex-1-yl) oxycarbonyloxy] ethyl iodide. Nuclear magnetic resonance (CDCI3) d: 0.80-0.93 (4H, m), 1.20, 1.21 (3H total, d of each, J = 7.4Hz), 1.28, 1.30 (3H total, d of each, J = 6.3 Hz), 1.52, 1.58 (3H total, d of each, J = 5.5Hz), 1.58 (3H, d, J = 5.5Hz), 1.62-1.73 (2H, m), 1.90-2.15 (4H, m) , 3.23-3.28 (HH, m), 3.35-3.42 (HH, m), 3.42 (3H, s), 4.18-4.30 (3H, m), 6.83-6.92 (HH, m), 7.01 (1H, s) , 8.0K1H, s), 8.32-8.37 (ÍH, m). MS (TSP): 518 (M + + H).

Example 63 - (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em- Cyclopentyloxycarbonyloxymethyl 3-carboxylate In the same manner as in Example 52, 54.4 milligrams of the header compound were obtained from 61.6 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) - 2- (sodium imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate and 69.7 milligrams of cyclopentyloxycarbonyloxymethyl iodide. Nuclear Magnetic Resonance (CDCI3) d: 1.21 (3H, d, J = 7.1Hz), 1.29 (3H, d, J = 6.1Hz), 1.48-1.58 (2H, m), 1.63-1.85 (5H, m), 3.25-3.30 (ÍH,), 3.35-3.42 (1H, m), 4.20-4.38 (4H, m), 5.00-5.08 (HH, m), 5.82 (1H, d, J = 5.7Hz), 5.88 (1H , d, J = 5.7Hz), 7.00 (1H, s), 7.99 (1H, s), 8.32 (1H, s). MS (TSP): 476 (M + + H).

Example 64 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em- 3-carboxylate of (Z) -2- (3-phtalidylidene) ethyl _ _ _ _ In the same manner as in Example 52, 36.8 milligrams of the header compound were obtained from 58.0 milligrams of (1S, 5R, 6S ) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate sodium and 81.2 milligrams of (Z) -3- (2-bromoethylidene) phthalide. Nuclear Magnetic Resonance (CDCI3) d: 1.30 (3H, d, J = 7.3Hz), 1.38 (3H, d, J = 6.2Hz), 3.33-3.50 (3H, m) 4.29-4.38 (2H, m), 5.18 -5.30 (2H, m), 5.80-5.85 (HH, m), 7.08 (1H, s), 7.21-7.26 (2H, m), 7.91-7.95 (HH, m), 8.06 (1H, s), 8.39 (1H, s). MS (TSP): 492 (M + + H).

Example 65 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em- 3-carboxylate of (IR, 2S, 5R) - (1) -mentyloxycarbonyloxymethyl In the same manner as in Example 52, 80.40 milligrams of the header compound were obtained from 64.4 milligrams of (IS, 5R, 6S) -6 - ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate sodium and 92.5 milligrams of iodide (IR, 2S, 5R) - (1) -mentyloxycarbonyloxymethyl. Nuclear Magnetic Resonance (CDCI3) d: 0.67 (3H, d, J = 6.9Hz), 0.79 (3H, d, J = 6.9Hz), 0.84 (3H, d, J = 6.6Hz), 0.90-1.05 (2H, m), 1.22 (3H, d, J = 7.5Hz), 1.30 (3H, d, J = 6.3Hz), 1.38-1.45 (1H, m), 1.56-1.65 (2H, m), 1.80-1.93 (3H , m), 2.00-2.08 (1H,), 3.22-3.28 (ÍH, m), 3.33-3.45 (1H, m), 4.19-4.30 (2H, m), 4.42-4.51 (ÍH, m), 5.83 ( 1H, d, J = 5.8Hz), 5.90 (1H, d, J = 5.8Hz), 7.00 (1H, s), 7.98 (1H, s), 8.33 (lH, s). MS (APCI): 546 (M + + H).

Example 66 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em- (1S, 2R, 5S) - (d) -mentyloxycarbonyloxymethyl 3-carboxylate In the same manner as in Example 52, 89.2 milligrams of the header compound were obtained from 61.7 milligrams of (IS, 5R, 6S) -6 - ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate sodium and 90.0 milligrams of iodide (SS, 2R, 5S) - (d) -mentyloxycarbonyloxymethyl. Nuclear Magnetic Resonance (CDCI3) d: 0.70 (3H, d, J = 7.1Hz), 0.81 (3H, d, J = 7.2Hz), 0.83 (3H, d, J = 7.1Hz), 0.90-1.05 (2H, m), 1.21 (3H, d, J = 7.1Hz), 1.29 (3H, d, J = 6.0Hz), 1.32-1.43 (1H, m), 1.55-1.62 (2H, m), 1.80-2.03 (4H , m), 3.23-3.28T1H, m), 3.36-3.42 (ÍH, m), 4.18-4.30 (2H, m), 4.41-4.52 (1H, m), 5.83 (1H, d, J = 5.8Hz) , 5.90 (1H, d, J = 5.8Hz), 7.00 (1H, s), 7.98 (1H, s), 8.33 (1H, s). MS (APCI): 546 (M + + H).

Example 67 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em- 3- (phenyloxycarbonyloxy) ethyl 3-carboxylate (diastereomeric mixture) In the same manner as in Example 52, 43.3 milligrams of the header compound was obtained from 63.8 milligrams of (1S, 5R, 6S) -6- (( IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate sodium and 268.6 milligrams of iodide of 1 - (phenyloxycarbonyloxy) ethyl. Nuclear Magnetic Resonance (CDCI3) d: 1.25-1.35 (3H, m), 1.38-1.45 (3H, m), 1.67-1.73 (3H total, d of each, J = 5.5Hz), (5Hm), 3.32 -3.50 (1H, m), 4.25-4.40 (2H, m), 7.00-7.06J1H, m), 7.07 (1H, s), 7.18-7.42 (5H, m), 8.04 (1H, s), 8.41 ( ÍH, s). MS (TSP): 498 (M + + H).

Example 68 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em- Phenyloxycarbonyloxymethyl 3-carboxylate In the same manner as in Example 52, 79.0 milligrams of the heading compound a - were obtained. from 63.5 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-1-carbapen Sodium 2-em-3-carboxylate and 101.9 milligrams of phenyloxycarbonyloxymethyl iodide. Nuclear magnetic resonance (CDCI3) d: 1.24 (3H, d, J = 7.1Hz), 1.34 (3H, d, J = 6.3Hz), 3.31-3.45 (3H, m), 4.28-4.40 (2H, m), 5.95 (1H, d, J = 5.8Hz), 6.10 (1H, d, J = 5.8Hz), 7.05 (1H, s), 7.25-7.40 (5H, m), 8.04 (1H, s), 8.31 (1H , s). MS (TSP): 484 (M + + H).

Example 69 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em- 1 ^ (cyclohexyloxycarbonyloxy) -n-propyl 3-carboxylate (diastereomeric mixture) In the same manner as in Example 52, 60.0 milligrams of the header compound were obtained from 61.3 milligrams of (IS, 5R, 6S) -6 - ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate sodium and 100.8 milligrams of 1- (Exoxycarbonyloxy) -n-propyl iodide. Nuclear magnetic resonance (CDCI3) d: 1.01, 1.08 (total 3H, t of each, J = 7.4Hz), 1.28, 1.30 (3H total, d of each, J = 7.1Hz), 1.36, 1.39 (3H of each, d of each - one, J = 6.6Hz), 1.42-1.80 (6H, m), 1.85-2.05 (4H, m), 3.30-3.46 (2H, m), 4.25-4.35 (2H, m), 4.60-4.72 (1H, m), 6.78-6.84 (1H, m), 7.08 (1H, s), 8.03 (1H, s), 8.44, 8.46 (1H total, s of each). MS (TSP): 518 (M + + H).

Example 70 Acid (SS, 5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- (T1R) -1-hydroxyethyl) -l-methyl-l-carbapen-2- em-3-carboxylic a) (SS, 5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), 92 milligrams of (SS, 5R, 6S) -2- (5-carbamoylimidazo [5] were obtained. , lb] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl from 251 milligrams of (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 364 milligrams of 5-carbamoyl-2- (tri -n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear magnetic resonance (DMSO-dg): 1.17 (3H, d, J = 7.0Hz), 1.20 (3H, d, J = 6.3Hz), 3.42 (1H, m), 3.72 (1H, m), 4.04 (1H , m), 4.34 (1H, m), 5.14 (1H, d, J = 4.7Hz), 5.37 (1H, d, - - J = 13.8Hz), 5.49 (1H, d, J = 13.8Hz), 7.23 (1H, s), 7.52 (1H, br.s), 7.70 (2H, d, J = 8.2Hz), 7.81 (1H, br.s), 8.19 (2H, d, J = 8.2Hz), 8.71 (ÍH, s). b) Acid (IS, 5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen -2-em-3-carboxylic acid In the same manner as in Example 5-b), 23.9 milligrams of the header compound were obtained from 92 milligrams of (IS, 5R, 6S) -2- (5-carbamoylimidazo [ 5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1.24 (3H, d, J = 7.1Hz), 1.33 (3H, d, J = 6.3Hz), 3.50 (1H, m), 3.58 (1H,) , 4.30 (2H, m), 7.10 (1H, s), 8.21 (1H, s.

Example 71 (SS, 5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2- pivaloyloxymethyl em-3-carboxylate In the same manner as in Example 19, 9.8 milligrams of the header compound were obtained from 15.7 milligrams of (SS, 5R, 6S) -2- (5-carbamoylimidazo [5, lb] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate.

Nuclear Magnetic Resonance (CDC13) d: 1.22 (9H, s), 1.33 (3H, d, J = 7.2Hz), 1.37 (3H, d, J = 6.3Hz), 3.35 (1H, dd, Jl = 6.3Hz, J2 = 2.7HZ), 3.66. { 1H, m), 4.30 (1H, m), 4.37 (1H, dd, Jl = 9.5Hz, J2 = 2.7Hz), 5.58 (HI, br.s), 5.89 (1H, d, J = 5.5Hz), 5.99 (1H, d, J = 5.5Hz), 7.00 (1H, br.s), 7.15 (1H, s), 8.73 (1H, s).

Example 72 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -l-carbapen-2-em-3-carboxylic acid potassium a ) (3S, 4R,) -1- [(allyloxycarbonyl) (triphenylphosphoranylidene) methyl] -3- [(IR) -1- (t-butyldimethyl-1-yloxy) ethyl] -4- [(pivaloyloxycarbonyl) methyl] azetidin-2-one. To a solution of 0.65 gram of (3S, 4R) -1- [(allyloxycarbonyl) (triphenylphosphoranylidene) methyl] -3 - [(lR) -l- (t-butyldimethylsilyloxy) ethyl] -4- (carbomethyl) azetidinone in 4 milliliters of toluene were added under cooling with ice, 0.14 milliliter of triethylamine and 0.12 milliliter of pivaloyl chloride, and the mixture was stirred at room temperature. The resulting precipitated material was collected by filtration and the filtrate was purified by column chromatography on silica gel (hexane: ethyl acetate = 2: 1) to give 0.60 gram of (3S, 4R) -1- [(allyloxycarbonyl ) (triphenylphosphoranilidene) - methyl] -3-1 (IR) -1- (t-butyldimethylsilyloxy) ethyl] -4- [(pivaloyloxycarbonyl) methyl] azetidin-2-one. Nuclear Magnetic Resonance (CDC13) d: -0.05 (3H, s), 0.80 (9H, s), 1.06 (3H, d, J = 6.0Hz), 2.52-2.62 (HH, m), 2.73-2.95 (2H, m), 4.03-4.20 (ÍH, i? i), 4.40-4.67 (2H, m), 5.10-5.35 (2H, m), 5.87-5.98 (1H, m), 7.43-7.85 (15H,). b) (5R, 6S) -6- [(IR) -1- (t-butyldimethylsilyloxy) ethyl] -2- (imidazo [5, 1-b] thiazol-5-yl) -l-carbapen-2-em Allyl -3-carboxylate In the same manner as in Example 48-b), 0.31 gram of (5R, 6S) -6- [(IR) -1- (t-butyldimethylsilyloxy) ethyl] -2- ( Allyl imidazo [5, 1-b] thiazol-5-yl) -1-carbapen-2-em-3-carboxylate from 1.52 grams of (3S, 4R) -1- [(allyloxycarbonyl) (triphenylphosphoranylidene) ethyl] ] -3- [(IR) -1- (t-Butyldimethylsilyloxy) ethyl] -4- [(pivaloyloxycarbonyl) methyl] azetidin-2-one. Nuclear magnetic resonance (CDC13) d: 0.10 (6H, s), 0.90 (9H, s), 1.28 (3H, d, J = 6.0Hz), 3.22 (HI, dd, J = 2.9, 6.2Hz), 3.35 ( 1H, dd, J = 8.8, 18.6Hz), 3.60 (1H, dd, J = 10.0, 18.6Hz), 4.22-4.32 (2H, m), 4.70-4.75 (2H, m), 5.20-5.38 (2H, m), 5.80-5.94 (1H, m), 6.91 (1H, d, J = 4.2Hz), 7.12 (1H, d, J = 4.2Hz), 7.30 (lH, s). c) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -l-carbapen-2-em-3-carboxylate of allyl In the same manner as in Example 48-c), 72 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazole- Allyl-5-yl) -l-carbapen-2-em-3-carboxylate from 0.31 g of (5R, 6S) -6- [(IR) -1- (t-butyldimethylsilyloxy) ethyl] -2- ( Allyl imidazo [5, 1-b] thiazol-5-yl) -l-carbapen-2-em-3-carboxylate. Nuclear Magnetic Resonance (CDC13) d: 1.40 (3H, d, J = 6.3Hz), 3.30 (3H, dd, J = 3.0, 6.6Hz), 3.40 (ÍH, dd, J = 12.0, 18.7Hz), 3.60 ( 1H, dd, J = 10.0, 18.7Hz), 4.24-4.36 (2H, m), 4.64-4.82 (2H, m), 5.20-5.36 (2H, m), 5.81-5.94 (HI, m), 6.92 ( 1H, d, J = 4.2Hz), 7.10 (1H, d, J = 4.2Hz), 7.31 (1H, s). d) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-5-yl) -l-carbapen-2-em-3-carboxylate from potassium In the same manner as in Example 48-d), 49 milligrams of the header compound of 172 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5 Allyl, 1-b] thiazol-5-yl) -l-carbapen-2-em-3-carboxylate. Nuclear Magnetic Resonance (D2?) D (HOD = 4.80ppm): 1.32 (3H, d, J = 6.5Hz), 3.22 (3H, dd, J = 10.1, 17.8Hz), 3.48 (1H, dd, J = 9.0 , 17.8Hz), 3.56 (1H, dd, J = 2.8, 5.8Hz), 4.25-4.44 (2H, m), 7.11 (1H, d, J = 4.1Hz), 7.19 (1H, s), 7.27 (H) , d, J = 4.1Hz). Example 73 - - _. - (5R, 6S) -6- ((IR) -l-hydroxyethyl-2- (imidazo [5, 1-b] thiazol-5-yl) -l-carbapen-2-em-3-carboxylate of pivaloyloxymethyl In the same manner as in Example 50, 20 milligrams of the header compound was obtained from (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazole- 5-yl) -l-carbapen-2-em-3-carboxylate to potassium, nuclear magnetic resonance (CDC13) d: 1.20 (9H, s), 1.38 (3H, d, J = 6.4Hz), 3.38 (3H, dd, J = 9.1, 19.8Hz), 3.60 (1H, dd, J = 9.9, 19.8Hz), 4.23-4.48 (2H, m), 5.84 (1H, d, J = 5.5Hz), 5.95 (1H, d , J = 5.5Hz), 6.96 (1H, d, J = 4.3Hz), 7.13 (1H, d, J = 4.3Hz), 7.33 (ÍH, s).

Example 74 acid (SS, 5R, 6S) -2- (5-formylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2 -em-3-carboxylic. • a) (SS, 5R, 6S) -2- (5-formylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen -2-em-3-carboxylate 4-nitrobenzyl To a suspension of 292 milligrams of acid (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2- em-3-carboxylate in 20 milliliters of dichloromethane 936 milligrams of manganese dioxide were added and the mixture was stirred at room temperature for two days. The dioxide of - - Manganese was removed by filtration and the filtrate was purified by column chromatography on silica gel (dichloromethane: methanol = 20: 1) to provide 148 milligrams of (SS, 5R, 6S) -2- (5-formylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (CDC13) d: 1.36 (3H, d, J = 7.4Hz), 1.40. { 3H, d, J = 6.2Hz), 3.40 (1H, dd, Jl = 6.4Hz, J2 = 2.9Hz), 3.67 (1H, m), 4.32 (1H, m), 4.41 (ÍH, dd, Jl = 9.3 Hz, J2 = 2.9Hz), 5.31 (1H, d, J = 13.4Hz), 5.55 (1H, d, J = 13.4Hz), 7.4K1H, s), 7.68 (2H, d, J = 8.8Hz), 8.24 (2H, d, J = 8.8Hz), 8.82 (ÍH, s), 9.75 (1H, s). b) acid (SS, 5R, S) -2- (5-formylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen -2-em-3-carboxylic acid In the same manner as in Example 5-b), 34.7 milligrams of the header compound were obtained from 115 milligrams of (IS, 5R, 6S) -2- (5-formyyl idazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1.23 (3H, d, J = 6.9Hz), 1.34 (3H, d, J = 6.3Hz), 3.51 (1H, m), 3.59 (1H, m ), 4.30 (2H, m), 7.37 (1H, s), 8.32 (1H, s), 9.40 (ÍH, s).

- - Example 75 (1S, 5R, 6S) -2- (5-formylimidazo [5, lb] thiazol-2-yl) -6- ((1R) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em- Pivaloyloxymethyl 3-carboxylate In the same manner as in Example 19, 33.2 milligrams of the header compound were obtained from 40.0 milligrams of acid (IS, 5R, 6S) -2- (5-formylimidazo [5, 1-b] ] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -1-methyl-l-carbapen-2-em-3-carboxylic acid. Nuclear Magnetic Resonance (CDC13) d: 1.22 (9H, s), 1.34 (3H, d, J = 7.4Hz), 1.37 (3H, d, J = 6.2Hz), 3.37 (1H, dd, Jl = 6.4Hz, J2 = 2.9HZ), 3.67 (1H, m), 4.30 (1H, m), 4.39 (1H, dd, Jl = 9.6Hz, J2 = 2.9HZ), 5.90 (1H, d, J = 5.6Hz), 6.00 (1H, d, J = 5.6Hz), 7.42 (1H, s), 8.80 (1H, s).

Example 76 Acid (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) 2- (7-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen- 2- em-3-carboxylic acid a) (1S, 5R, 6S) -2- (7-t-butyldimethylsilyloxymethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) 1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl - - In the same manner as in Example 5-a), 392.6 milligrams of (SS, 5R, 6S) -2- (7-t-butyldimethylsilyloxymethylimidazo [5, 1-b] thiazol-2-yl) -6- were obtained. ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl from 598.9 milligrams of (IR, 3R, 5R, 6S) -6- ((IR ) -1-hydroxyethyl) -l-methyl-2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 1.03 grams of 7-t-butyldimethylsilyloxymethyl-2- (tri-n-butylstannyl) imidazo [5, 1 -b] thiazole. Nuclear Magnetic Resonance (CDC13) d: 0.14, 0.16 (6H total, s of each), 0.97, 1.09 (9H total, s of each), 1.30 (3H, d, J = 7.2Hz), 1.40 (3H, d, J = 6.2Hz), 3.35-3.39 (HH, m), 4.43-3.51 (HH, m), 4.28-4.40 (2H, m), 4.88, 4.89 (2H total, s of each), 5.27 ( ÍH, d, J = 14.0Hz), 5.52 (ÍH, d, J = 14.0Hz), 7.51 (1H, s), 7.68 (2H, d, J = 8.9Hz), 7.95 (1H, s), 8.24 ( 2H, d, J = 8.9Hz), 8.33 (1H, s). b) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7- (hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-1-carbapen -2-em-3-carboxylate of 4-nitrobenzyl _ To a solution of 334, .6 of (1S, 5R, 6S) -2- (7-t-butyldimethylsilyloxymethylimidazo [5, 1-b] thiazol-2-yl ) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 10 milliliters of THF were added 0.28 milliliters of acetic acid and 1.64 milliliters of a 1 M solution of tetra-n-butylammonium fluoride in THF, - and the mixture was stirred at room temperature for 2.5 hours. After the reaction mixture was adjusted to a pH of 8.2 with a saturated aqueous sodium hydrogen carbonate solution, it was extracted twice with ethyl acetate and a semi-saturated aqueous saline solution. The organic layer was dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained in this way was purified by column chromatography on silica gel (ethyl acetate: methanol = 9: 1) to give 183 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl ) -2- (7-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (CDC163) d: 1.29 (3H, d, J = 6.8Hz), 1.39 (3H, d, J = 6.2Hz), 2.92-3.00 (HI, m), 3.36 (1H, dd, Jl = 6.6 Hz, J2 = 2.7Hz), 3.38-3.50 (1H, m), 4.29-4.39 (2H, m), 4.77 (2H, s), 5.27 (ÍH, d, J = 13.8Hz), 5.52 (1H, d , J = 13.8Hz), 7.67 (2H, d, J = 8.9Hz), 7.98 (1H, s), 8.23 (2H, d, J = 8.9Hz), 8.31 (ÍH, s). c) Acid (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen -2-em-3-carboxylic acid In the same manner as in Example 5-b), 87.7 milligrams of the header compound were obtained from 139.9 milligrams of (IS, 5R, 6S) -6- ((IR) - 1- - - hydroxyethyl) -2- (7-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (D20) d (HOD = 4.80ppm): 1.25 (3H, d, J = 7.1Hz), 1.31 (3H, d, J = 6.3Hz), 3.50-3.61 (2H, m), 4.24-4.32 (2H, m), 4.66 (2H, s), 7.89 (1H, s), 8.11 (1H, s).

Example 77 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -l-methyl-l- carbapen-2-em-3-carboxylate (internal salt) a) iodide of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 4-a), 68.1 milligrams of (1S , 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -l-methyl-1-carbapen- 4-Nitrobenzyl 2-em-3-carboxylate from 54.5 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (CD30D) d: 1.22 (3H, d, J = 6.3Hz), 1.26 (3H, d, J = 7.4Hz), 3.24 (3H, s), 3.60-3.68 (ÍH, - - m), 3.96 (2H, s), 4.03-4.12 (1H, m), 4, 31-4.36 (1H, m), 5.25 (1H, d, J = 13.7Hz), 5.42 (1H, d, J = 13.7Hz), 7.63 (2H, d, J = 8.8Hz), 8.11 (2H, d, J = 8.8Hz), 8.42 (1H, s), 9.29 (1H, s). b) (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -1-methyl -l-carbapen-2-em-3-carboxylate (inner salt) In the same manner as in Example 4-b), 16.9 milligrams of the header compound were obtained from 68.1 milligrams of (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethyl-6-methylimidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3 -carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D2?) D (HOD = 4.80ppm): 1.24 (3H, d, J = 7.2Hz), 1.30 (3H, d, J = 6.3Hz), 3.51-3.67 (3H, m), 4.01 ( 2H, s), 4.21-4.33 (1H, m), 4.86 (2H, s), 8.06 (1H, s), 9.14 (1H, s).

Example 78 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-7-yl) -l-methyl-l-carbapen-2-em- 3-carboxylic acid potassium a) (3S, 4R) -1- (allyloxycarbonyl) (triphenylphosphoranylidene) methyl-3- ((IR) -1-t-butyldimethylsilyloxyethyl) -4- [(IR) -1- (imidazo [5 , 1-b] thiazol-7-yl-carbonyl) ethyl] azetidin-2-one.

- - To a solution of 540 milligrams of 7-iodoimidazo [5, 1-b] thiazole in 16 milliliters of THF was added 2.4 milliliters of a 1M solution of ethylmagnesium bromide in THF under ice cooling under an argon atmosphere and the mixture it was stirred at room temperature for 30 minutes. After confirming the exhaustion of the starting materials, the reaction mixture was cooled from -35 ° C to -40 ° C and a solution of 1.64 grams of (3S, 4R) -1- is slowly added to the reaction mixture. (allyloxycarbonyl) (triphenylphosphoranylidene) methyl-3- ((IR) -1-t-butyldimethylsilyloxyethyl) -4- [(IR) -1- (pivaloyloxycarbonyl) ethyl] azetidin-2-one in 10 milliliters of THF. After 15 minutes, the reaction mixture was placed in an ice bath and stirred for three hours. It was diluted with 25 milliliters of saturated ammonium and extracted four times with 25 milliliters of ethyl acetate. The organic layer was washed twice with 30 milliliters of saturated aqueous saline, dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained in this way was purified by column chromatography on silica gel (hexane: ethyl acetate = 1: 4-ethyl acetate), to give 570 milligrams of (3S, R) -1- (allyloxycarbonyl) (triphenylphosphoranilidene) meti1-3- ((IR) -1-t- - - butyldimethylsilyloxyethyl) -4- [(IR) -1- (imidazo [5, 1-b] thiazol-7-yl-carbonyl) ethyl] azetidin-2-one. Nuclear Magnetic Resonance (CDC13) d: -0.2-0.0 (6H, m), 0.6-0.8 (9H, m), 0.8-1.5 (6H, m), 2.7-3.4 (3H, m), 4.0-4.7 (3H , m), 5.0-5.4 (2H, m), 5.8-6.0 (lH, m), 7-8 (18H, m). b) (SS, 5R, 6S) -6- ((IR) -1-t-butyldimethylsiloxyethyl) -2- (imidazo [5, 1-b] thiazol-7-yl) -l-methyl-l-carbapen- Allyl 2-em-3-carboxylate _ To a solution of 276 milligrams of (3S, 4R) -1- (allyloxycarbonyl) (triphenylphosphoranylidene) methyl-3- ((IR) -1-t-butyldimethylsilyloxyethyl) -4- [ (IR) - (imidazo [5, 1-b] thiazol-7-yl-carbonyl) ethyl] azetyl-2-one in 8 milliliters of xylene was added 8 milligrams of hydroquinone and the mixture was heated to 125 ° C. After cooling, the reaction mixture was purified by column chromatography on silica gel (hexane: ethyl acetate = 1: 1-1: 3) to provide 145 milligrams of (SS, 5R, 6S) -6- ((IR) - Allyl 1-t-butyldimethylsilyloxyethyl) -2- (imidazo [5, 1-b] thiazol-7-yl) -1-methyl-l-carbapen-2-em-3-carboxylate. Nuclear Magnetic Resonance (CDC13) d: 0.10 (6H, m), 0.90 (9H, s), 1.20 (3H, d, J = 7.2Hz), 1.32 (3H, d, J = 6.2Hz), 3.25 (1H, dd, Jl = 6.9Hz, J2 = 2.6HZ), 3.9-4.3 (3H, m), 4.8 (2H, m), 5.3-5.4 (2H, m), 6.0 (1H, m), 7.03 (1H, d) , J = 4.3Hz), 7.50 (1H, d, J = 4.3Hz), 8.10 (1H, s). c) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-7-yl) -l-methyl-l-carbapen-2- allyl-3-carboxylate To a solution of 460 milligrams of (SS, 5R, 6S) -6- ((IR) -1-t-butyldimethylsilyloxyethyl) -2- (imidazo [5, 1-b] thiazole-7 allyl-1-methyl-l-carbapen-2-em-3-carboxylate in 14 milliliters of THF were added 860 milliliters and 3.76 milliliters of 1 M tetra-n-butylammonium fluoride and THF, and the mixture was stirred at room temperature for 2 days. The reaction mixture was diluted with 120 milliliters of ethyl acetate, washed with 30 milliliters of a semi-saturated aqueous saline solution and then with 30 milliliters of a mixed solution of the semi-saturated aqueous saline solution and a sodium carbonate solution. saturated aqueous sodium hydrogen (1: 1), dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained in this way was purified by silica gel column chromatography (dichloromethane: methanol = 97: 3-95: 5) to provide 286 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazole) -7-yl) allyl methyl-1-carbapen-2-em-3-carboxylate. Nuclear magnetic resonance (CDC13) d: 1.21 (3H, d, J = 7.2Hz), 1.39 (3H, d, J = 6.3Hz), 3.30 (ÍH, dd, J? = 6.9Hz, J2 = 2.5HZ), 4.0 (1H, m), 4.2-4.4 (2H, m), 4.83 (2H, m), 5.2- - . 5 (2H, m), 6.0 (1H, m), 7.04 (1H, d, J = 4.3Hz), 7.53 (1H, d, J = 4.3Hz), 8.12 (1H, s). d) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-7-yl) -l-methyl-l-carbapen-2- potassium em-3-carboxylate To a solution of 117 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, lb] thiazol-7-yl) - Allyl 1-methyl-l-carbapen-2-em-3-carboxylate in a mixed solvent of 2.5 milliliters of dichloromethane and 2.5 milliliters of ethyl acetate was added 8.1 milligrams of triphenylphosphine, 56.5 milligrams of potassium 2-ethylhexanoate and 11.8 milligrams of tetrakis (triphenylphosphine) palladium (0), and the mixture was stirred under an argon atmosphere at room temperature for 20 minutes. After confirming the exhaustion of the starting materials, the reaction mixture was diluted with 10 milliliters of ethyl acetate, extracted three or four times with water and the aqueous layer was concentrated under reduced pressure. The concentrated material was purified by column chromatography on COSMOSEAL 40C18-PREP to provide the header compound in a yield of 55 milligrams. Nuclear magnetic resonance (D2?) D (HOD = 4.80 ppm): 1.13 (3H, d, J = 7.2Hz), 1.34 (3H, d, J = 6.3Hz), 3.37 (1H, dd, Jl = 6.5Hz, J2 = 2Hz), 5.53 (1H, m), 4.17 (ÍH, dd, Jl = 8.6Hz, - J2 = 2HZ), 4.26 (1H, m), 7.17 (HH, d, J = 4.1Hz), 7.69 (1H, d, J = 4.1Hz), 8.26 (HH, s).

Example 79 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (6-methylimidazo [5, 1-b] thiazol-7-yl) -l-methyl-l-carbapen-2- em-3-carboxylate (inner salt) To a solution of 77 milligrams of (SS, 5R, 6S) -6- ((IR) -hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-7-yl) Allyl-1-methyl-carbapen-2-em-3-carboxylate in dichloromethane 37 milligrams of trifluoromethanesulfonic acid were added dropwise under ice-cooling. After confirming the exhaustion of the starting materials, the solvent was removed under reduced pressure. The residue was triturated with 2.4 milliliters of trichloromethane and 2.4 milliliters of ethyl acetate followed by about 1 milliliter of acetonitrile to form a homogeneous solution to which was added 5.2 milligrams of triphenylphosphine and 36.5 milligrams of potassium 2-ethylhexanoate followed by tetrakis ( triphenylphosphine) palladium (0), for an additional 40 minutes of stirring at room temperature. The reaction mixture was diluted with 10 milliliters of dichloromethane and extracted twice with 20 milliliters of water. The aqueous layer was concentrated and the residue was- purified by column chromatography on DIAION HP-20 (water - water: acetone = 10: 1) and in COSMOSEAL 40C18 PREP (water: acetonitrile = 95: 5 - 90: 10) in this sequence, to provide 5.8 milligrams of the header compound. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.09 (3H, d, J = 7.4Hz), 1.31 (3H, d, J = 6.5Hz), 2.58 (1H, m), 3.5-3.7 (2H) , m), 3.96 (3H, s), 4.30 (1H, m), 4.45 (1H, dd, Jl = 10.2Hz, J2 = 3.0Hz), 7.53 (ÍH, d, J = 4.2Hz), 7.92 (1H , d, J = 4.2Hz), 9.31 (ÍH, s).

Example 80 (5R, 6S) -2- (7-chloroimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate from sodium a) (5R, 6S) -2- (7-chloroimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 4-Nitrobenzylcarboxylate In the same manner as in Example 5-a), (5R, 6S) -2- (7-chloroimidazo [5, 1-b] thiazol-2-yl) -6- (( IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate 4-nitrobenzyl as a yellow powder in a yield of 507 milligrams from 887 milligrams of (3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-oxo-l-carbapen-2-em-3-carboxylate - - of 4-nitrobenzyl and 1,254 grams of 7-chloro-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear magnetic resonance (DMS0-d6) d: 1.17 (3H, d, J = 6.3Hz] 3.40-3.50 (2H, m 3.52 (ÍH, dd, Jl = 6.1Hz, J2 = 3.1HZ), 3.97 (HH, m), 4.25 (1H, dt, J? = 10.3Hz, j2 = 2.8Hz), 5.17 (HH, d, J = 4.9Hz), 5.42 (HH, d, J = 13.7Hz), 5.54 (HH, d, J = 13.7Hz), 7.76 (2H, d, J = 8.5Hz), 8.22 (HH, s), 8.25 (2H, d, J = 8.5Hz), 8.36 ( ÍH, s). MS (TSP): 489 (M + + H). b) (5R, 6S) -2- (7-chloroimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 sodium carboxylate In the same manner as in Example 134-d), except that the purifion was carried out in CHP-20P (2 percent THF in water), 113 milligrams of the header compound were obtained from 245 milligrams of (5R, 6S) -2- (7-chloroimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.30 (1H, d, J = 6.3Hz), 3.21-3.25 (2H, m), 3.51 (1H, dd, Jl = 5.9Hz, J2 = 2.9Hz), 4.20-4.26 (2H, m 7.21 (ÍH, s) 8.00 (1H, s).

Example 81 Acid (5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- - - ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid a) (5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6 - ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), 108 milligrams of (5R, 6S) - 2- (5-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid 4-nitrobenzyl ester from 170 milligrams of (3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 267 milligrams of 5-carbamoyl-2- (tri) -n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear Magnetic Resonance (DMSO-d6) d: 1.17 (3H, d, J = 6.3Hz), 3.53 (3H, m), 4.03 (1H, m), 4.27 (1H, m), 5.15 (1H, d, J = 5.0Hz), 5.42 (HH, d, J = 13.8Hz), 5.54 (HH, d, J = 13.8Hz), 7.23 (1H, s), 7.53 (1H, br.s), 7.76 (2H, d , J = 8.7Hz), 7.83 (1H, br.s), 8.24 (2H, d, J = 8.7Hz), 8.63 (1H, s). b) (5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 acid -carboxylic acid In the same manner as in Example 5-b), 34.7 milligrams of the header compound were obtained from 105 milligrams of (5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazole- 2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl.

- - Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.33 (3H, d, J = 6.1Hz), 3.28 (2H, m), 3.53 (1H, m), 4.28 (2H, m), 7.10 (1H) , s), 8.00 (1H, s).

Example 82 (5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1- idroxyethyl) -l-carbapen-2-em-3-carboxylate of pivaloyloxymethyl In the same manner as in Example 19, 12.2 milligrams of the header compound of 35.8 milligrams of (5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-2-yl) - acid were obtained. 6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid. Nuclear Magnetic Resonance (CDC13) d: 1.24 (9H, s), 1.37 (3H, d, J = 6.3Hz), 3.33 (1H, dd, Jl = 6.3Hz, j2 = 2.8Hz), 3.46 (2H, m) , 4.30 (2H, m), 5.60 (1H, br.s), 5.91 (1H, d, J = 5.5Hz), 6.03 (1H, d, J = 5.5Hz), 6.98 (1H, br.s), 7.13 (1H, s), 8.56 (1H, s).

Example 83 (SS, 5R, 6S) -2- (5-formyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l- carbapen-2-em-3- _ __ carboxylate (internal salt) - To a suspension of 33 milligrams of (1S, 5R, 6S) -2- (5-formylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl 4-nitrobenzyl-l-carbapen-2-em-3-carboxylate in 1 milliliter of chloromethane was added 0.017 milliliter of methyl trifluoromethanesulfonate under ice-cooling. The mixture was stirred for 5 hours and concentrated under reduced pressure. The residual concentrate material was dissolved in 2 milliliters of THF and two milliliters of a 1/15 M sodium phosphate stabilizer (pH of 6.6) and 47 milligrams of 10 percent Pd-C were added thereto. The reactor was purged with hydrogen and the reaction mixture was stirred at room temperature for 2 hours. The catalyst was collected by filtration on Celite and washed with water. The filtrate was washed with ethyl acetate and the aqueous layer was purified by column chromatography on DIAION HP-20 (20 percent methanol in water) and COSMOSEAL 40C18-PREP (water: methanol = 10: 1) to provide 2.5 milligrams of the header compound. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.27 (3H, d, J = 6.9Hz), 1.32 (3H, d, J = 6.3Hz), 3.57 (HH, m), 3.64 (HH, m ), 4.07 (3H, s), 4.29 (1H, m), 4.35 (1H, m), 7.52 (1H, s), 8.09 (1H, s), 9.12 (1H, s).

Example 84 - - (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-7-yl) -l-methyl-l-carbapen-2-em- Pivaloyloxymethyl 3-carboxylate To a solution of 27 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-7-yl) - Sodium 1-methyl-l-carbapen-2-em-3-carboxylate in 0.5 milliliter of DMF was added 4.0 milligrams of sodium hydrogencarbonate and the mixture was cooled to -30 ° C under the argon atmosphere. Pivaloyloxymethyl iodide (30 milligrams) was added and then the reaction stirring was stirred at -20 ° C to -30 ° C for 1 hour. The reaction mixture was diluted with 20 milliliters of ethyl acetate and 10 milliliters of a semi-saturated aqueous saline solution and the mixture was stirred and separated. The organic layer was washed with a semi-saturated aqueous saline solution, dried through anhydrous magnesium sulfate and the solvent was concentrated under reduced pressure to a volume of about 1 milliliter. It was purified by column chromatography on silica gel (ethyl acetate-ethyl acetate: methanol = 97: 3), and the solvent was concentrated under reduced pressure to a volume of about 0.5 milliliter and added dropwise to isopropyl ether. . The resulting precipitated material was collected by filtration and dried under pressure - - reduced to provide 17 milligrams of the header compound. Nuclear magnetic resonance (CDC13) d: 1.23 (9H, s), 1. 24 (3H, d, J = 7.9Hz), 1.38 (3H, d, J = 6.3Hz), 3.29 (1H, dd, Jl = 6.6Hz, J2 = 2.5HZ), 3.98 (1H, m), 4.2-4.4 (2H, m), 5.96 (1H, d, J = 5.5Hz), 6.05 (1H, d, J = 5.5Hz) , 7.02 (ÍH, d, J = 4.2Hz), 7. 54 (1H, d, J = 4.2Hz), 8.12 (1H, s).

Example 85 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7- (hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-1-carbapen-2 pivaloyloxymethyl-3-carboxylate In the same manner as in Example 19, there were obtained 7.5 milligrams of the heading compound of 58.5 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) - 2- (7-hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylic acid. Nuclear magnetic resonance (CDCI3) d: 1.14 (9H, s), 1.20 (3H, d, J = 7.4Hz), 1.29 (3H, d, J = 6.2), 3.25 (1H, dd, J? = 6.6Hz, J2 = 2.7HZ), 3.25-3.40 (HI, m), 4.18-4.28 (2H, m), 4.71 (2H, s), 5.81 (1H, d, J = 5.6Hz), 5.91 (1H, d, J = 5.6Hz), 6.64 (1H, s), 7.95 (1H, s), 8.25 (lH, s).

Example 86 - (5R, 6S) -2- (7-chloro-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em- 3-carboxylate (inner salt) In the same manner as in Example 4-a) except that 98 milligrams of (5R, 6S) -2- (7-chloroimidazo [5, 1-b] thiazol-2-yl) - 6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and a mixed solvent of dichloromethane and DMF (1: 1), iodide of (5R, 6S) -2- (7-chloro-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen- Crude 4-nitrobenzyl 2-em-3-carboxylate was obtained as a yellowish brown oil in a yield of 99 milligrams. In the same manner as in Example 4-b) except that a portion of 61.0 milligrams of the crude product was used in the reaction, and the purification was carried out with CHP-20P (10 percent methanol in water), obtained the compound of the heading in a yield of 7.5 milligrams as a pale yellow flocculated. Nuclear magnetic resonance (D2?) D (HOD = 4.80 ppm): 1.3s (3H, d, J = 6.3Hz), 3.45 (2H, m), 3.56 (1H, dd, Jl = 6.1Hz, J2 = 3.0Hz ), 4.00 (3H, s), 4.22-4.35 (2H, m), 7.97 (1H, s), 8.44 (0.2H, s, partially exchanged with D2O). MS (FAB +): 370 (M + + 3), 368 (M + + 1).

Example 87 - (5R, 6S) -2- (7-chloroimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate from pivaloyloxymethyl In the same manner as in Example 135, the title compound was obtained in a yield of 41 milligrams as a yellow powder from 58 milligrams of (5R, 6S) -2- (7-chloroimidazo [5, 1-] b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate sodium. Nuclear Magnetic Resonance (CDC13) d: 1.22 (9H, s), 1.36 (3H, d, J = 6.3Hz), 3.25-3.35 (3H, m), 4.22-4.37 (2H, m), 5.90 (1H, d) , J = 5.6Hz), 6.01 (1H, d, J = 5.6Hz), 7.92 (1H, s), 8.18 (ÍH, s). MS (FAB +): 470 (M + + 3), 468 (M + + 1).

Example 88 (5R, 6S) -2- (6-carbamoylmethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 carboxylate (inner salt) a) (5R, 6S) -2- (6-carbamoylmethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2 4-Nitrobenzyl-3-carboxylate To a suspension of 69 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazole-2-) il) -1-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 2 milliliters of acetone were added 281 milligrams of - - iodoacetamide, and the mixture was stirred at room temperature for 25 hours. The reaction mixture was concentrated under reduced pressure to dryness. The residue was triturated with 3 milliliters of ethyl acetate and the insoluble materials were collected by filtration to provide (5R, 6S) -2- (6-carbamoylmethylimidazo [5, 1-b] thiazolium-2-yl) iodide. - ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (DMSO-d6) d: 1.18 (3H, d, J = 6.1Hz), 3.45 (3H, m), 4.03 (1H, m), 4.32 (1H, m), 5.17 (2H, s), 5.45 (3H, m), 4.03 (1H, m), 4.32 (1H, m), 5.17 (2H, s), 4.45 (1H, d, J = 13.8Hz), 5.55 (1Hm, J = 13.8Hz) , 7.08 (1H, br.s), 7.63 (1H, br.s), 7.75 (2Hm d, J = 8.5Hz), 7.83 (1H, s), 8.25 (2H, d, J = 8.5Hz), 8.60 (1H, s), 9.55 (1H, s). b) (5R, 6S) -2- (6-carbamoylmethylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 carboxylate (inner salt) In the same manner as in Example 4-b), the header compound was obtained in a yield of 11.2 milligrams of the whole amount of (5R, 6S) -2- (6-carbamoylmethylimidazo [5, lb] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl.

- Nuclear magnetic resonance (D2O) d (HOD = 480 ppm): 1. 30 (3H, d, J = 6.5Hz), 3.32 (2H, m), 3.54 (1H, dd, Jl = 5.6Hz, J2 = 2.8HZ), 4.296 (2H, m), 5.24 (2H, s), 7.53 (1H, s), 7.94 (ÍH, s).

Example 89 (SS, 5R, 6S) -2- (5,7-dimethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- Sodium 2-em-3-carboxylate a) (1S, 5R, 6S) -2- (5,7-dimethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1- hydroxyethyl) -l-methyl-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), (ÍS, 5R, 6S) -2- (5,7-dimethylimidazo) was obtained [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 365 milligram as a dark yellow powder from 544 milligrams of (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -1-methyl-2-oxo-l-carbapen-2-em 3-Nitrobenzyl carboxylate and 728 milligrams of 5,7-dimethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear Magnetic Resonance (DMSO-dβ) d: 1.18 (3H, d, J = 6.6Hz), 1.21 (3H, d, J = 7.8Hz), 2.14 (3H, s), 2.45 (3H, s), 3.34- 3.41 (1H, m), 3.65-3.77 (ÍH, m), 3.97-4.05 (ÍH, m), - 4. 30 (1H, dd, Jl = 9.5Hz, J2 = 2.6Hz), 5.15 (1H, d, J = 5.0Hz), 5.37 (IH, d, J = 13.8), 5.50 (IH, d, J = 13.8Hz ), 7.72 (2H, d, J = 8.8Hz), 8.21 (1H, s), 8.22 (2H, d, J = 8.8). MS (TSP): 497 (M + + H). b) (SS, 5R, 6S) -2- (5,7-dimethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-carbapen- Sodium 2-em-3-carboxylate In the same manner as in Example 134-d) except that 224 milligrams of (SS, 5R, 6S) -2- (5,7-dimethylimidazo [5, 1-b] thiazole -2-il) -6- ((IR) -1-hydroxyethyl) -1-methyl-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and 224 milligrams of 10 percent palladium on carbon were used and the purification was carried out in HP-20 (20 percent methanol in water) and in COSMOSEAL 40C18-PREP (10 percent methanol in water), the compound of the heading was obtained in a yield of 103 milligrams. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.24 (3H, d, J = 6.9Hz), 1.31 (3H, d, J = 6.6Hz), 2.28 (3H, s), 2.65 (3H, s) ), 3.50-3.65 (2H, m), 4.24-4.35 (2H, m), 7.79 (1H, s) MS (TSP): 384 (M + + Na), 362 (M + + H).

Example 90 - (SS, 5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-carbapen-2-em- Sodium 3-carboxylate a) (SS, 5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl -carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), (S, 5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] was obtained thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 0.46 gram from 0.36 gram of (IR , 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2-oxo-l-carbapen-3-carboxylate of 4-nitrobenzyl and 0.47 g of 7-formylaminomethyl-2- ( tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear magnetic resonance (CDC13) d: 1.27 (3H, d, J = 7.4Hz), 1.38 (3H, d, J = 6.3Hz), 3.34 (1H, dd, J = 2.8, 6.6Hz), 3.45 (1H, m), 4.25. { 1H, m), 4.45 (1H, dd, J = 2.8, 9.4Hz), 4.49 (2H, s), 5.29 (1H, d, J = 13.5Hz), 5.50 (1H, d, J = 13.5), 7.66 (2H, d, J = 8.5), 8.00 (HH, s), 8, 19 (1H, s), 8.22 (2H, d, J = 8.5), 8.30 (HH, s). b) (SS, 5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-carbapen-2- sodium em-3-carboxylate In the same manner as in Example 134-d), the title compound was obtained in a yield of 58 - - milligrams of 0.27 gram (IS, 5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l- carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.22 (3H, d, J = 7.1Hz), 1.31 (3H, d, J = 6.3Hz), 3.45-3.60 (2H, m), 4.20-4.30 (2H, m), 4.43 (2H, s), 7.84 (1H, s), 8.05 (1H, s), 8.16 (1H, s).

Example 91 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -carbapen-2-em-3-carboxylic acid acetoxymethyl ester To one solution of 60.2 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -carbapene-2-em-3-carboxylate from sodium in 1.4 milliliters of DMF was added 67.7 milligrams of acetoxymethyl bromide under the argon atmosphere, at a temperature of -30 ° C, and the mixture was stirred for 3 hours through which period the temperature was raised to 10 ° C . The reaction mixture was diluted twice with 20 milliliters of ethyl acetate and washed twice with 10 milliliters of semi-saturated aqueous saline. The organic layer was dried through anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to a volume of 2 - - milliliters. The residue obtained in this way was purified by silica gel column chromatography (dichloromethane: methanol = 15: 1) and Sephadex LH-20 (dichloromethane: methanol = 1: 1) in this sequence to provide 22.1 milligrams of the header compound . Nuclear Magnetic Resonance (CDC13) d: 1.39 (3H, d, J = 6.3Hz), 2.10 (3H, s), 3.32-3.40 (3H, m), 4.25-4.34 (HH, m), 4.37-4.45 (HH) , m), 5.78 (1H, d, J5.6Hz), 5.86 (1H, d, J = 5.6Hz), 7.13 (2H, s), 7.79 (1H, s). MS (TSP): 392 (M + + H).

Example 92 (5R, 6S) -2- (imidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate from 1 (acetoxy) ethyl (diastereomeric mixture) [In the same manner as in Example 91, the compound was obtained in a yield of 21.2 milligrams from 56.4 milligrams of (5R, 6S) -6- ((IR) - 1-hydroxyethyl) -2- (sodium imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate and 70.6 milligrams of sodium iodide 1 (acetoxy) ethyl. Nuclear magnetic resonance (CDC13) d: 1.35-1. 8 (6H, m), 2. 05-2.10 (3H, m), 3.30-3.41 (3H, m), 4.23-4.32 (1H, m), 4.36-4.45 (1H, m), 6.85-6.92 (ÍH, m), 7.08, 7.10 (1H total, s of - - each), 7.12 (ÍH, s), 7.83, 7.84 (1H total, s of each). MS (TSP): 406 (M + + H).

Example 93 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of (1) -methylcylohexan-1-yl) carbonyloxymethyl In the same manner as in Example 91, the header compound was obtained in a yield of 55.5 milligrams from 62.5 milligrams (5R), 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -1-carbapen-2-em-3-carboxylic acid sodium and 69.8 milligrams of (1-methyl-1-yloxan-1-yl) carbonyloxymethyl iodide. Nuclear Magnetic Resonance (CDC13) d: 1.15-1.25 (3H, m), 1.36 (3H, s), 1.37 (3H, d, J = 6.3Hz), 1.40-1.56 (3H, m), 1.93-2.06 (2H , m), 3.31-3.29 (3H, m), 4.25-4.33 (ÍH,), 4.37-4.45 (1H, m), 5.82 (1H, d, J = 5.5Hz), 5.87 (1H, d, J = 5.5Hz), 7.12 (ÍH, s), 7.14 (1H, s), 7.82 (1H, s). MS (TSP): 474 (M + + H).

Example 94 - - (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of (1) -ethoxycarbonyloxy) ethyl (diastereomeric mixture) __ In the same manner as in Example 91, the heading compound was obtained in a yield of 28.4 milligrams from 60.0 milligrams of (5R, 6S) -6- ((IR) - 1-hydroxyethyl) -2- (sodium imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate and 85.9 milligrams of 1- (ethoxycarbonyloxy) ethyl iodide. Nuclear Magnetic Resonance (CDC13) d: 1.21-1.36 (6H, m), 1.40-1.46 (3H, m), 3.24-3.32 (3H, m), 4.12-4.28 (3H, m), 4.30-4.39 (1H, m), 6.71-6.47 (HH, m), 7.05 (2H, s), 7.75 (1H, s). MS (TSP): 436 (M + + H).

Example 95 (5R 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of 1 - (isopropoxycarbonyloxy) ethyl (diastereomeric mixture) To a solution of 48 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) ) -1-carbapen-2-em-3-carboxylate sodium in 1 milliliter of DMF was added 73 milligrams of 1- (isopropoxycarbonyloxy) ethyl iodide under the argon atmosphere at -20 ° C, and the mixture was stirred for 3 hours through which period of time the temperature rose to -10 ° C.

The reaction mixture was extracted twice with 20 milliliters of ethyl acetate and washed twice with 10 milliliters of a semi-saturated aqueous saline solution.The organic layer was dried through anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to a volume of 2 milliliters The residue obtained in this way was purified by column chromatography on silica (chloroform: methanol = 9: 1) and on Sephadex LH-20 (dichloromethane: methanol = 1: 1) in this sequence, to provide the compound of the header in a yield of 22 milligrams Nuclear magnetic resonance (CDC13) d: 1.28-1.47 (12Hz, m), 3.24-3.42 (3H, m), 4.21-4.47 (2H, m) , 6.67-6.88 (HH, m), 7.10 (1H, s), 7.13 (1H, s), 7.85 (1H, s), MS (TSP): 450 (M + + H).

Example 96 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate from 1- (cyclohexyloxycarbonyloxy) ethyl (diastereomeric mixture) In the same manner as in Example 95, the title compound was obtained in a yield of 45 milligrams from 48 milligrams of (5R, 6S) -6- ((IR) iodide -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -1- - - sodium carbapen-2-em-3-carboxylate and 63 milligrams of 1- (cyclohexyloxycarbonyloxy) ethyl iodide. Nuclear Magnetic Resonance (CDC13) d: 1.20-1.67 (12H, m), 1.68-1.84 (2H,), 1.86-2.20 (1H, m), 3.24-3.45 (3H, m), 4.22-4.48 (2H, m ), 4.57-4.71 (1H, m), 6.77-6.88 (ÍH,), 7.11, 7.12 (1H total, s of each), 7.14 (1H, s), 7.84, 7.85 (1H total, s of each) ). MS (TSP): 490 (M + + H).

Example 97 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of _ __ cyclohexyloxycarbonyloxymethyl In the same manner as in Example 91, the title compound was obtained in a yield of 39. 5 milligrams from 61.7 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -1-carbapen-2- sodium em-3-carboxylate and 69.8 milligrams of cyclohexyloxycarbonyloxymethyl iodide. Nuclear Magnetic Resonance (CDC13) d: 1.23-1.98 (10H, m), 1.38 (3H, d, J = 6.2Hz), 3.33-3.42 (3H, m), 4.26-4.36 (H, m), 4.36-4.46 (lH, m), 4.00-4.70 (1H, m), 5.80 (1H, d, J = 5.7Hz), 5.88 (1H, d, J = 5.7Hz), 7.13 (1H, s), 7.18 (1H, s), 7.83 (1H, s).

- - MS (TSP): 476 (M + H).

Example 98 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of 3- phthalidyl (diastereomeric mixture) In the same manner as in Example 95, the title compound was obtained in a yield of 24 milligrams from 42 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (sodium imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate and 39 milligrams of 3-phthalidyl bromide. Nuclear magnetic resonance (CDC13) d: 1.36, 1.37 (total HI, d each, J = 6.3Hz), 3.13-3.45 (3H, m), 4.21-4.50 (2H,), 6.98, 6.99 (1H total, s of each), 7.10, 7.25 (1H total, s of each uino), 7.40 (1H, s), 7.80, 7.87 (total HI, s of each), 7.35-7.91 (4H, m). MS (TSP): 452 (M + + H).

Example 99 (5R, 6S) -6- ((1R) -l-hydroxyethyl) -2- (imidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of -methyl-2-oxo-l, 3-dioxolen-4-yl) methyl- In the same manner as in Example 91, the header compound was obtained in a yield of 15.9 milligrams from 65.3 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (imidazo) [5, 1-b] thiazol-3-yl) -1-carbapen-2-em-3-carboxylic acid sodium and 65.8 milligrams of 5-methyl-2-oxo-l-3-dioxolen-4- bromide il) methyl. Nuclear magnetic resonance (CDC13) d: 1.39 (3H, d, J = 6.3Hz), 2.78 (3H, s), 3.35-3.40 (3H, m), 4.29-4.34 (HI, m), 4.38-4.46 (lH , m), 4.90 (1H, s), 4.91 (1H, s), 7.03 (1H, s), 7.12 (IH, s), 7.73 (IH, s). MS (TSP): 476 (M + + H).

Example 100 (SS, 5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2- pivaloyloxymethyl em-3-carboxylate To a solution of 33 milligrams of (1S, 5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1 sodium hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate in 0.8 milliliter of DMF was added 29 milligrams of pivaloyloxymethyl iodide at 30 ° C, and the mixture was stirred for 1 hour through whose time the temperature rose to room temperature. The reaction mixture was diluted with 30 milliliters of dichloromethane, washed with a semi-saturated aqueous saline solution and dried through anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue obtained in this way was purified by column chromatography on silica gel (ethyl acetate: methanol = 4: 1) to provide the title compound- in a yield of 29 milligrams. Nuclear magnetic resonance (CDC13) d: 1.20 (9H, s), 1.24 (3H, d, J = 7.2Hz), 1.34 (3H, d, J = 6.2Hz), 3.31 (HH, dd, J = 2.8, 6.5 Hz), 3.41 (1H, m), 3.49 (2H, s), 4.25-4.35 (2H, m), 4.45-4.60 (2H, m), 5.86 (1H, d, J = 5.6Hz), 5.98 (1H , d, J = 5.6Hz), 6.72 (1H, br.ss), 8.00 (1H, s), 8.26 (1H, s), 8.34 (ÍH, s).

Example 101 (5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate from sodium a) (5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 4-Nitrobeczylcarboxylate In the same manner as in Example 5-a), (5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] thiazol-3-yl) -6- ( (IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 0.70 gram from - - 0. 42 grams of (3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 0.47 g of 7-formylaminomethyl-3- (tri) -n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear Magnetic Resonance (DMSO-d6) d: 1.17 (3H, d, J = 6.0Hz), 3.15-3.30 (2H, m), 3.50-3.62 (HH, m), 3.95-4.05 (HH, m), 4.25 -4.33 (3H, m), 5.28 (1H, d, J = 13.5Hz), 5.33 (1H, d, J = 13.5Hz), 7.37 (1H, s), 7.52 (2H, d, J = 8.3Hz) , 7.96 (1H, s), 8.14 (1H, s), 8.17 (2H, d, J = 8.3Hz). b) (5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 sodium carboxylate In the same manner as in Example 134-d), the title compound was obtained in a yield of 27 milligrams from 0.55 gram of (5R, 6S) -2- (7-formylaminomethylimidazo [5,1] -b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D2?) D (HOD = 4.80 ppm): 1.32 (3H, d, J = 6.3Hz), 3.20 (3H, dd, J = 2.9, 5.9Hz), 3.40 (1H, m), 3.58 ( 1H, dd, J = 2.9, 5.9Hz), 4.23-4.30 (ÍH,), 4.32-4.4K1H, m), 4.50 (2H, s), 7.05 (1H, s), 7.94 (1H, s), 8.17 (ÍH, s).

Example 102 - - (5R, 6S) -2- (7-formylaminomethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate from pivaloyloxymethyl In the same manner as in Example 50, the title compound was obtained in a yield of 24 milligrams from 45 milligrams of (5R, 6S) -2- (7-formylaminomethylimidazo [5, lb] thiazole-3-) il) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate sodium. Nuclear Magnetic Resonance (D2?) D (HOD = 4.80 ppm): 1.20 (9H, s), 1.35 (3H, d, J = 6.2Hz), 3.29-3.40 (3H,), 4.22-4.32 (1H, m) , 4.35-4.44 (ÍH, m), 4.50 (2H, d, J = 5.6Hz), 5.73 (1H, d, J = 5.6Hz), 5.83 (1H, d, J = 5.6Hz), 6.85 (1H, t, J = 5.6Hz), 7.06 (1H, s), 7.72 (1H, s), 8.22 (1H, s).

Example 103 Acid (5R, 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid a) (5R, 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3- 4-nitrobenzyl carboxylic acid In the same manner as in Example 5-a), 124 milligrams of (5R, 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazol-3-yl) -6 were obtained - ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl from - - 255 milligrams of (3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-oxo-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and 401 milligrams of 7-carbamoyl- 3- (tri-n-butylstannyl) imidazo [5, 1-b] triazole. Nuclear Magnetic Resonance (CDC13) d: 1.41 (3H, d, J = 6.1Hz), 3.39 (3H, m), 4.32 (1H, m), 4.46 (1H, m), 5.21 (1H, d, J = 13.0 Hz), 5.37 (1H, d, J = 13.0Hz), 7.17 (IH, s), 7.47 (2H, d, J = 8.7Hz), 7.56 (1H, s), 8.19 (2H, d, J = 8.7 Hz). b) (5R, 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 acid -carboxylic acid In the same manner as in Example 5-b), the header compound was obtained in a yield of 42.3 grams from 124 milligrams of (5R, 6S) -2- (7-carbamoylimidazo [5,1]) -b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1.33 (3H, d, J = 6.5Hz), 3.23 (HI, dd, Jl = 17.0Hz, J2 = 9.9HZ), 3.48 (1H, dd, Jl = 17.0Hz, J2 = 8.5HZ), 3.60 (1H, m), 4.29 (1H, m), 4.40 (1H, m), 7.21 (1H, s), 7.87 (1H, s).

Example 104 (5R, 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate from - - pivaloyloxymethyl In the same manner as in Example 19, the title compound was obtained in a yield of 14.1 milligrams from 44.6 milligrams of the (5R, 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazole acid -3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid. Nuclear Magnetic Resonance (CDC13) d: 1.19 (9H, s), 1.37 (3H, d, J = 6.3Hz), 3.38 (3H, m), 4.29 (1H, m), 4.43 (1H,), 5.71 (1H) , broad s), 5.77 (ÍH, d, J = 5.5Hz), 5.88 (1H, d, J = 5.5Hz), 6.91 (1H, br.s), 7.21 (1H, s), 7.71 (1H, s ).

Example 105 (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (5,6,7-trimethylimidazo [5, 1-b] thiazolium-2-yl) -l- carbapen-2-em-3-carboxylate (internal salt) __ _ a) iodide of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -1-methyl-2- (5,6) , 7-trimethylimidazo [5, 1-b] thiazolium-2-yl) -1-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 4-a), 121.3 milligrams were obtained of (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (5,6-7-trimethylimidazo [5, 1-b] thiazolium-2-yl) -l 4-nitrobenzylcarbapene-2-em-3-carboxylate as a yellowish-orange powder from 99.3 milligrams of (IS, 5R, 6S) -2- (5, 7-) dimethylimidazo [5, lb] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and 1.0 milliliter of iodide of methyl. Nuclear Magnetic Resonance (DMSO-d6) d: 1.18 (3H, d, J = 6.3Hz), 1.23 (3H, d, J = 7.2Hz), 2.44 (3H, s), 2.83 (3H, s), 3.48 ( ÍH, dd, Jl = 5.9Hz, J2 = 2.9Hz), 3.73-3.84 (ÍH, m), 3.80 (3H, s), 4.02-4.09 (ÍH, m), 4.39 (1H, dd, Jl = 10.1Hz , J2 = 2.9HZ), 5.19 (1H, d, J = 5.2Hz), 5.40 (1H, d, J = 13.8Hz), 5.52 (1H, d, J = 13.7Hz), 7.73 (2H, d, J = 8.8Hz), 8.24 (2H, d, J = 8.8), 8.59 (ÍH, s). MS (TSP): 511 (M +). b) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- (5,6,7-trimethylimidazo [5, 1-b] thiazolium-2-yl) - l-carbapen-2-em-3-carboxylate (internal salt) In the same manner as in Example 4-b), except that 115 milligrams of iodide of (ΔS, 5R, 6S) -6- ((IR 1-hydroxyethyl) -l-methyl-2- (5,6-7-trimethylimidazo [5, 1-b] thiazolium-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl , and that the purification was carried out in CHP-20P (20 percent - 30 percent methanol in water) and in COSMOSEAL 40C18-PREP (20 percent methanol in water) the compound of the heading was obtained in a yield of 9.1 milligrams as a milk white flocculate.

Nuclear Magnetic Resonance (D2O) d (HOD = 4.80 ppm): 1.26 (3H, d, J = 7.1Hz), 1.31 (3H, d, J = 6.5Hz), 2.39 (3H, s), 2.76 (3H, s) ), 3.55 (1H, dd, Jl = 6.2Hz, J2 = 2.8HZ), 3.57-3.67 (1H, m), 3.79 (3H, s), 4.28 (ÍH, quintet, J = 6.2Hz), 4.34 (ÍH) , dd, Jl = 9.3Hz, j2 = 2.8Hz), 7.92 (1H, s). MS (TSP): 376 (M + + H).

Example 106 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate from sodium a) (5R, 6S) -2- (7-t-butyldimethylsilyloxymethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em 3-nitriobenzyl carboxylate In the same manner as in Example 5-a), (5R, 6S) -2- (7-t-butyldimethylsilyloxymethylimidazo [5, 1-b] thiazol-3-yl was obtained) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 1.53 grams from 994.3 milligrams of (3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-oxo-l-carbapenam-3-carboxylate of 4-nitriobenzyl and 1.76 grams of 7-t-butyldimethylsilyloxymethyl-3- (tri-n-butylstannyl) imidazo [5, 1-] b] thiazole.

- Nuclear Magnetic Resonance (CDC13) d: 0.14 (6H, s), 0.96 (9H, s), 1.37 (3H, d, J = 6.3Hz), 1.48 (1H, br.s, s), 3.33--3.40 ( 3H, m), 4.26-4.33 (ÍH, m), 4.39-4.47 (1H, m), 4.83 (2H, s), 5.19 (1H, d, J = 13.5Hz), 5.33. { 1H, d, J = 13.5Hz), 7.02 (1H, s), 7.39 (2H, d, J = 8.9Hz), 7.74 (1H, s), 8.14 (2H, d, J = 8.9Hz). MS (TSP): 599 (M +). b) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3 4-Nitrobenzyl carboxylate To a solution of 848.8 milligrams of (5R, 6S) -2- (7-t-butyldimethylsilyloxymethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl ) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 20 milliliters of THF were added in 1.22 milliliters of acetic acid and 7.1 milliliters of a 1M solution of tetra-n-butylammonium fluoride in THF, and The mixture was stirred at room temperature for 2.5 hours. After neutralizing the mixture with a saturated aqueous solution of sodium hydrogencarbonate, it was extracted twice with ethyl acetate, washed with a semi-saturated aqueous saline solution and dried through anhydrous magnesium sulfate and the solvent was added. removed under reduced pressure. The residue obtained in this way was purified by column chromatography on silica gel (ethyl acetate: methanol = 9: 1) to provide - - 324. 3 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3 -carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (CDC13) d: 1.29 (3H, d, J = 6.3Hz), 3.40-3.48 (3H, m), 4.18-4.28 (HH, m), 4.32-4.40 (HH, m), 4.15 (2H) , s), 5.13 (2H, d, J = 13.9Hz), 5.28 (2H, d, J = 13.9Hz), 6.98 (1H, s), 7.35 (2H, d, J = 8.7Hz), 7.12 (1H, s), 810 (2H, d, J = 8.7Hz). MS (TSP): 485 (M + + H). c) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3 sodium carboxylate In the same manner as in Example 134-d), the title compound was obtained in a yield of 57.7 milligrams from 157.0 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl ) -2- (7-hydroxymethylimidazo [5, lb] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1. 32 (3H, d, J = 6.4Hz), 3.10-3.27 (HH, m), 3.41-3.50 (1H, m), 3.57-3.61 (HH, m), 4.20-4.40 (2H, m), 4.76 ( 2H, s), 7.23 (1H, s), 8.26 (1H, s).

Example 107 - (SS, 5R, 6S) -2- (7-formylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2- sodium em-3-carboxylate a) (SS, 5R, 6S) -2- (7-formyl-idazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) - l-Methyl-l-carbapen-2-em-3-carboxylic acid 4-nitrobenzyl To a solution of 183.0 milligrams of (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7 -hydroxymethylimidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 15 milliliters of dichloromethane, 596.7 milligrams of manganese dioxide were added and The mixture was stirred at room temperature for 38 hours. The catalyst was removed by filtration in Celite and the filtrate was removed under reduced pressure. The residue obtained in this way was purified by column chromatography on silica gel (ethyl acetate: methanol = 9: 1) to provide 127 milligrams of (S), 5R, 6S) -2- (7-formylimidazo [5, 1-b] thiazole-2-11) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em- 4-Nitrobenzyl 3-carboxylate. Nuclear magnetic resonance (CDC13) d: 1.24 (3H, d, J = 7.2Hz), 1.32 (3H, d, J = 6.3Hz), 3.34 (IH, dd, Jl = 6.4Hz, J2 = 2 7HZ), 3.41 -4.50 (ÍH, m), 4.21-4.32 (1H, m), 4.37 (ÍH, dd, Jl = 9.6Hz, J2 = 2.7HZ), 5.20 (1H, d, J = 13.7Hz), 5.45 (1H, d, J = 13.7Hz), 7.59 (2H, d, J = 8.4Hz), 8.02 (1H, s), 8.14 (2H, d, J = 8.4Hz), 8.42 (1H, s), 9.83 (1H, s). - b) (1S, 5R, 6S) -2- (7-formylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- Sodium 2-em-3-carboxylate In the same manner as in Example 134-d), the title compound was obtained in a yield of 56. 7 milligrams from 127.0 milligrams of (ΔS, 5R, 6S) -2- (7-formylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen-2- em-3-carboxylate of 4-nitrobenzyls. Nuclear Magnetic Resonance (D20) d (HOD: 4.80 ppm): 1.19 (3H, d, J = 6.6Hz), 1.32 (3H, d, J = 5.9Hz), 3.46-3.60 (2H, m), 4.21-4.34 (2H, m), 7.94 (1H, s), 8.12 (1H, s), 9.41 (1H, s). Example 108 (1S, 5R, 6S) -2- (7-formylimidazo [5, lb] thiazol-2-yl) -6- ((1R) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em- Pivaloyloxymethyl 3-carboxylate In the same manner as in Example 135, the title compound was obtained in a yield of 26.0 milligrams from 31.4 milligrams of (1S, 5R, 6S) -2- (7-formylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate sodium.

- - Nuclear magnetic resonance (CDC13) d: 1.19 (9H, s), 1. 33 (3H, d, J = 7.2Hz), 1.36 (3H, d, J = 6.3Hz), 3.35-3.40 (HI,), 3.49-3.56 (lH, m), 4.23-4.27 (1H, m), 4.41 (1H, dd, J? = 9.2Hz, J2 = 2.8Hz), 5.87 (1H, d, J = 5.7), 5.99 (1H, d, J = 5.7Hz), 8.11 (1H, s), 9.91 (1H, s).

Example 109 Acid (SS, 5R, 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2 -em-3-carboxylic acid a) (SS, 5R, 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l- methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), (1S, 5R, 6S) -2- (7-carbamoylimidazo [5]) was obtained , 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 109 milligrams at from 215 milligrams of acid (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 324 milligrams of 7-carbamoyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] triazole. Nuclear magnetic resonance (CDC13) d: 1.30 (3H, d, J = 7.4Hz), 1.40 (3H, d, J = 6.3Hz), 3.38 (ΔH, dd, Jl = 6.6Hz, - J2 = 2.8HZ), 3.50 (1H, m), 4.32 (1H, m), 4.41 (1H, dd, Jl = 9.7Hz, J2 = 2.8HZ), 5.27 (ÍH, d, J = 13.5Hz), 5.52 (ÍH, d, J = 13.5Hz), 5.53 (1H, br.s), 6.78 (1H, br.s), 7.67 (2H, d, J = 8.9Hz), 8.50 (ÍH, s). b) Acid (IS, 5R, 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen -2-em-3-carboxylic acid In the same manner as in Example 5-b), the header compound was obtained in a yield of 73.8 milligrams from 123 milligrams of acid (1S, 5R, 6S) -2- (7-Carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.22 (3H, d, J = 7.1Hz), 1.33 (3H, d, J = 6.4Hz), 3.53 (2H, m), 4.30 (2H, m ), 7.92 (1H, s), 8.50 (1H, s).

Example 110 (SS, 5R, 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2- pivaloyloxymethyl em-3-carboxylate In the same manner as in Example 19, the title compound was obtained in a yield of 31.5 milligrams from 35.2 milligrams of the acid - - (1S, 5R, 6S) -2- (7-carbamoylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2- em-3-carboxylic acid. Nuclear Magnetic Resonance (CDC13) d: 1.20 (9H, s), 1.28 (3H, d, J = 7.4Hz), 1.37 (3H, d, J = 6.2Hz), 3.35 (HH, dd, Jl = 6.8Hz, J2 = 2.7HZ), 3.50 (IH, m), 4.28 (IH, m), 4.41 (1H, dd, Jl = 9.9Hz, J2 = 2.7Hz), 5.58 (IH, br.s), 5.87 (IH, d, J = 5.6Hz), 5.98 (1H, d, J = 5.6Hz), 6.92 (2H, br.s), 8.01 (1H, s), 8.51 (1H, s).

Example 111 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2- sodium a-3-carboxylate a) (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazol-2-yl) -l -methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), (1S, 5R, 6S) -6- ((IR) -1 was obtained -hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 550 milligrams at from 730 milligrams of (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2-oxo-l-carbapenam-3-carboxylate and 1010 grams of 7-methoxymethyl- 2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole.

- - Nuclear magnetic resonance (CDC13) d: 1.28 (3H, d, J = 7.3Hz), 1.37 (3H, d, J = 6.1Hz), 3.35 (3H, s), 3.3-3.5 (lH, m), 3.55 ( 1H,), 4.27 (ÍH, m), 4.37 (1H, dd, J? = 9.5Hz, J2 = 2.3HZ), 4.60 (2H, s), 5.27 (1H, d, J = 13.7Hz), 5.50 ( 1H, d, J = 13.7Hz), 7.65 (2H, d, J = 8.7Hz), 8.18 (1H, m), 8.20 (2H, d, J = 8.7Hz), 8.30 (ÍH, s). b) (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazol-2-yl) -l-methyl-1-carbapen- Sodium 2-em-3-carboxylate To a solution of 550 milligrams of (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazole -2-yl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 30 milliliters of THF and 30 milliliters of a 1/15 M phosphate stabilizer (pH of 6.8) were added 660 milligrams of 10 percent Pd-C and the mixture was stirred under the atmosphere of hydrogen at room temperature, for 1 hour. After filtering through Celite, the catalyst was washed with a THF: water mixture (eleven) . The combined filtrates were adjusted to a pH of 6.7 with a saturated aqueous sodium hydrogen carbonate solution washed with 30 milliliters of ethyl acetate and concentrated under reduced pressure. The residue obtained in this way was purified by column chromatography on DIAION HP-20 and lyophilized to provide 220 milligrams of a pulverized product. A portion of - 120 milligrams of the product was purified by column chromatography on COSMOSEAL 40C18-PREP to provide the header compound in a yield of 58 milligrams. Nuclear Magnetic Resonance (D2?) D (HOD: 4.80 ppm) 1.22 (3H, d, J = 7.1Hz), 1.31 (3H, d, J = 6.3Hz), 3.36 (3H, s), 3.50 (1H, dd , Jl = 6.1Hz, J2 = 2.6Hz), 3.54 (1H,), 4.26 (1H, m), 4.29 (1H, dd, Jl = 9.3Hz, j2 = 2.5Hz), 4.49 (2H, s), 7.84 (1H, s), 8.13 (ÍH, s).

Example 112 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazol-2-yl) -l-methyl-l-carbapen-2- pivaloyloxymethyl-3-carboxylate To a solution of 40 milligrams of (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazole-2 sodium) -l-methyl-l-carbapen-2-em-3-carboxylate in 0.6 milliliter of DMF was added 4.2 milligrams of sodium hydrogen carbonate and the mixture was cooled to -30 ° C under an atmosphere of argon. Pivaloyloxymethyl iodide (34 milligrams) was added and the mixture was stirred for 1 hour, diluted with 30 milliliters of ethyl acetate and washed with 20 milliliters of a saturated aqueous saline solution of 20 milliliters of a saline solution. semi-saturated aqueous. The organic layer was dried through anhydrous magnesium sulfate and concentrated under reduced pressure to a volume of about 1 milliliter. The concentrated material was purified by column chromatography on silica gel (chloroform: methanol = 95: 5) to give the title compound which was obtained in a yield of 18.4 milligrams. Nuclear Magnetic Resonance (CDC13) d: 1.21 (9H, s), 1.28 (3H, d, J = 7.2Hz), 1.36 (3H, d, J = 6.3Hz), 3.32 (1H, dd, Jl = 6.8Hz, J2 = 2.8Hz), 3.44 (3H, s), 3.4-3.5 (lH, m), 4.27 (1H, m), 4.34 (ÍH, dd, Jl = 9.7Hz, J2 = 2.8Hz), 4.58 (2H, s), 5.88 (ÍH, d, J = 5.7Hz), 5.93 (1H, d, J = 5.7Hz), 8.02 (1H, s), 8.33 (1H, s).

Example 113 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate from sodium a) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3 4-Nitrobenzylcarboxylate In the same manner as in Example 5-a), (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5,1] was obtained -b] thiazol-2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 450 - milligrams from 697 milligrams of (3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 896 milligrams of 7-methoxymethyl- 3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. b) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, -b] thiazol-3-yl) -carbapen-2-em-3-carboxylate sodium In the same manner as in Example 134-d), the title compound was obtained in a yield of 30 milligrams of ( 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazol-3-yl) -carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1.31 (3H, d, J = 6.3Hz), 3.33 (2H, m), 3.39 (3H, s), 3.59 (1H, dd, Jl = 5.8Hz , j2 = 2.3Hz), 4.2-4.4 (2H, m), 4.60 (2H, s), 7.13 (HH, s), 8.04 (HH, s).

Example 114 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate from pivaloyloxymethyl In the same manner as in Example 135, the title compound was obtained in a yield of 10 milligrams from 28 milligrams of (5R, 6S) -6- ((IR) -1- - - hydroxyethyl) -2- (7-methoxymethylimidazo [5, 1-b] thiazol-3-yl) -1-carbapen-2-em-3-carboxylate sodium. Nuclear magnetic resonance (CDC13) d: 1.19 (9H, s), 1.37 (3H, d, J = 6.3Hz), 3.3-3.4 (2H, m), 3.43 (3H, s), 4.27 (1H, s), 4.40 (1H, m), 5.78 (1H, d, J = 5.5Hz), 5.88 (1H, d, J = 5.5Hz), 7.14 (1H, s), 7.78 (lH, s).

Example 115 (5R 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate of pivaloyloxymethyl In the same manner as in Example 135, the header compound was obtained in a yield of 9.0 milligrams from 39.5 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7 Sodium hydroxymethylimidazo [5, 1-b] thiazol-3-yl) -l-carbapen-2-em-3-carboxylate. Nuclear magnetic resonance (CDC13) d: 1.20 (3H, d, J = 5.8Hz), 3.68-3.80 (3H, m), 4.90-5.05 (2H, m), 5.72 (1H, d, J = 6.0Hz), 5.88 (1H, d, Jl = 6.0Hz), 6.30- 6.42 (2H, m), 7.70 (1H, s), 9.60 (H, s).

Example 116 Acid (1S, 5R, 6S) -2- (7-cyanoimidazo [5, 1-b] thiazol-2-yl) -6- - ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylic acid a) (SS, 5R, 6S) -2- (7-cyanoimidazo [5, 1-b] thiazole- 2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), obtained (S, 5R, 6S) -2- (7-cyanoimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- 2-em-3-carboxylate 4-nitrobenzyl in a yield of 253 milligrams from 362 milligrams of acid (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl- 4-Nitrobenzyl 2-oxo-l-carbapenam-3-carboxylate and 526 milligrams of 7-cyano-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear magnetic resonance (CDC13) d: 1.32 (3H, d, J = 7.2Hz), 1.40 (3H, d, J = 6.3Hz), 3.49 (1H, dd, J? = 6.4Hz, J2 = 2.8Hz), 3.50 (HH, m), 4.32 (HH, m), 4.42 (HH, dd, J1 = 9.8Hz, J2 = 2.8HZ), 5.29 (HH, d, J = 13.7Hz), 5.53 (HH, d, J = 13.7Hz), 7.68 (2H, d, J = 8.9Hz), 8.01 (ÍH, s), 8.25 (2H, d, J = 8.9Hz), 8.37 (1H, s). b) Acid (1S, 5R, 6S) -2- (7-cyanoimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen -2-em-3-carboxylic acid In the same manner as in Example 5-b), the heading compound was obtained in a yield of 62.1 milligrams from (SS, 5R, 6S) -2- (7-cyanoimidazo [5, 1-b] - - thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D2O) d (HOD = 4.80 ppm): 1.23 (3H, d, J = 7.1Hz), 1.32 (3H, d, J = 6.2Hz), 3.51 (1H, m), 3.59 (1H,) , 4.29 (2H,), 8.00 (1H, s), 8.16 (1H, s).

Example 117 (SS, 5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1- _ hydroxyethyl) -l-methyl-1-carbapen-2 pivaloyloxymethyl-3-carboxylate In the same manner as in Example 19, the header compound was obtained in a yield of 34.3 milligrams from 36.7 milligrams of the acid (IS, 5R, 6S) -2- (7- cyanoimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylic acid. Nuclear magnetic resonance (CDCI3) d: 1.21 (9H, s), 1.30 (3H, d, J = 7.2Hz), 1.37 (3H, d, J = 6.3Hz), 3.37 (HI, dd, Jl = 6.5Hz, J2 = 3.0HZ), 3.50 (ÍH, m), 4.30 (ÍH, 'm), 4.41 (ÍH, dd, Jl = 9.9Hz, J2 = 3.0HZ), 5.87. { 1H, d, J = 5.6Hz), 5.99 (1H, d, J = 5.6Hz), 8.06 (1H, s), 8.37 (1H, s).

Example 118 Acid (SS, 5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2 -em-3-carboxylic acid a) (SS, 5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l- 4-Nitrobenzyl methyl-l-carbapen-2-em-3-carboxylate __ _ In the same manner as in Example ^ 5-a), (ΔS, 5R, 6S) -2- (7-ethylimidazo [ 5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 258 milligrams from 362 milligrams of (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2-oxo-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and 259 milligrams of 7-ethyl -2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear Magnetic Resonance (CDC13) d: 1.32 (6H, m), 1.40 (3H, d, J = 6.2Hz), 2.75 (2H, q, J = 7.6Hz), 3.36 (1H, dd, J = 6.5Hz) , J2 = 2.8Hz), 3.46 (1H, m), 4.33 (2H, m), 5.28 (1H, d, J = 13.7Hz), 5.52 (IH, d, J = 13.7Hz), 7.68 (2H, d , J = 8.6Hz), 7.94 (1H, s), 8.24 (2H, d, J = 8.6Hz), 8.26 (1H, s). b) (1S, 5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l- acid carbapen-2-em-3-carboxylic acid In the same manner as in Example 5-b) except that purification was carried out by column chromatography on DIAION HP-20 (10 percent methanol in water - 40 percent of methanol in water) and COSMOSEAL 40C18PREP (water: methanol = 5.5), the compound was obtained of the header in a yield of 31.7 milligrams from 164 milligrams of (SS, 5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1 -hydroxyethyl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D20) d (HOD = 4.80): 1.30 (9H, m), 2.82 (2H, q, J = 7.7Hz) 3.56 (1H, dd, Jl = 6.0Hz, J2 = 3.0HZ), 3.61 ( ÍH, m), 4.28 (ÍH, m), 4.34 (ÍH, dd, Jl = 9.4Hz, J2 = 3.0HZ), 8.02 (1H, s), 8.86 (1H, s).

Example 119 (SS, 5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2- pivaloyloxymethyl em-3-carboxylate In the same manner as in Example 19, the title compound was obtained in a yield of 15.8 milligrams from 45.3 milligrams of the acid (1S, 5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2- em-3-carboxylic acid. Nuclear Magnetic Resonance (CDC13) d: 1.21 (9H, s), 1.29 (3H, d, J = 7.2Hz), 1.32 (3H, d, J = 7.6Hz), 1.37 (3H, d, J = 6.2Hz) , 2.75 (2H, c, J = 7.6Hz), 3.32 (1H, dd, Jl = 6.0Hz, J2 = 2.8Hz), 3.44 (1H, m), 4.31 (2H, m), 5.88 (1H, d, J = 5.6Hz), 5.98 (1H, d, J = 5.6Hz), 7.97 (1H, s).

Example 120 Acid (5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -l-hydroxyethyl-1-carbapen-2-em-3-carboxylic acid a ) (5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -l-hydroxyethyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), (5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR ) -l-hydroxyethyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 27.8 milligrams from 239 milligrams of (3R, 5R, 6S) -6- ((IR) -1- hydroxyethyl) -2-oxo-l-carbapem-3-carboxylate of 4-nitrobenzyl and 376 milligrams of 5-carbamoyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole, nuclear magnetic resonance (CD30D) ) d: 1.31 (3H, d, J = 6.3Hz), 3.1-3.7 (3H, m), 4.1-4.4 (2H, m), 4.9-5.2 (2H, m), 7.30 (2H, m), 8.1 (2H, m) b) (5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -l-hydroxyethyl-1-carbapen- 2-em-3-carboxylic acid In the same manner as in Example 5-b), e was obtained The compound of the heading in a yield of 16.9 milligrams from 33.2 milligrams of (5R, 6S) -2- (5-carbamoylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1 -hydroxyethyl-l-carbapen-2-em-3-carboxylate of 4- - - nitrobenzyl. Nuclear magnetic resonance (D20) d (HOD = 4.80): 1.33 (3H, d, J = 6.3Hz), 3.15 (1H, dd, Jl = 17.6Hz, j2 = 9.9Hz), 3.27 (ÍH, dd, J? = 17.7Hz, j2 = 8.5Hz), 3.53 (ÍH, m), 4.30 (2H, m), 7.19 (1H, s), 7.2K1H, s).

Example 121 Acid (5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid a) (5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 4-Nitrobenzyl carboxylate In the same manner as in Example 5-a), (5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ( (IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 203 milligrams from 348 milligrams of acid (3R, 5R, 6S) -6- ((IR ) -1-hydroxyethyl) -2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 529 milligrams of 7-ethyl-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear Magnetic Resonance (CDC13) d: 1.31 (3H, t, J = 7.5Hz), 1.39 (3H, d, J = 6.3Hz), 2.74 (2H, q, J = 7.5Hz), 3.32 (3H, m) , 4.32 (2H, m), 5.30 (1H, d, J = 13.7Hz), 5.54 (1H, - - d, J = 13.7Hz), 7.68 (2H, d, J = 8.4Hz), 7.93 (1H, s), 8.15 (1H, s), 8.23 (2H, d, J = 8.4Hz). b) (5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 acid -carboxylic acid In the same manner as in Example 5-b), the header compound was obtained in a yield of 49.1 milligrams from 203 milligrams of (5R, 6S) -2- (7-ethylimidazo [5, 1-] b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -1-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D2?) D (HOD = 4.80 ppm): 1.31 (6H, m), 2.76 (2H, q, J = 7.5Hz), 3.31 (2H, m), 3.54 (1H, m), 4.28 ( 2H, m), 7.79 (1H, s), 8.58 (1H, s).

Example 122 (5R, 6S) -2- (7-ethylimidazo [5, lb] thiazol-2-yl) -6- ((1R) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of _ pivaloyloxymethyl In the same manner as in Example 19, the title compound was obtained in a yield of 23.3 milligrams from 43.0 milligrams of the acid (5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid. Nuclear magnetic resonance (CDC13) d: 1.23 (9H, s), 1.32 (3H, t, J = 7.6Hz), 1.36 (3H, d, J = 6.3Hz), 2.74 (2H, q, - - J = 7.6Hz), 3.29 (3H, m), 4.28 (2H, m), 5.91 (1H, d, J = 5.6Hz), 6.00 (1H, d, J = 5.6Hz), 7.96 (1H, s) 8.20 (1H, s).

Example 123 Acid (5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid __ a) (5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 4-Nitrobenzylcarboxylate In the same manner as in Example 5-a), the title compound was obtained in a yield of 765 milligrams from 627 milligrams (3R, 5R, 6S) -6- ((IR ) -1-hydroxyethyl) -2-oxo-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and 882 milligrams of 7-ethyl-3- (tri-n-butylstannyl) imidazo [5, 1-b ] thiazole Nuclear Magnetic Resonance (CDC13) d: 1.30 (3H, t), 1.38 (3H, d), 2.72 (2H, c), 3.25-3.45 (3H, m), 4.32 (1H, m), 4.33 (1H, m ), 5.28 (2H, ABq), 7.00 (1H, s), 7.42 (2H, d), 7.67 (HI, s), 8.17 (2H, d). b) (5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 acid -carboxylic acid In the same manner as in Example 5-b), the header compound was obtained in a yield of 86.6 milligrams from 203 milligrams of (5R, 6S) -2- (7-ethylimidazo [5, 1-] b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -1-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D2?) D (HOD = 4.80 ppm): 1.31 (6H, m), 2.80 (2H, c, J = 7.7Hz), 3.21 (ÍH, dd, J? = 17.3Hz, J2 = 10.1HZ ), 3.45 (1H, dd, Jl = 17.3Hz, j2 = 8.9Hz), 3.59 (HI, m), 4.29 (1H, m), 4.38 (1H, m), 7.25 (1H, s), 8.33 (1H) , s).

Example 124 5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of pivaloyloxymethyl In the same manner as in Example 19, the header compound was obtained in a yield of 29.1 milligrams from 41.6 milligrams of acid (5R, 6S) -2- (7-ethylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid. Nuclear magnetic resonance (CDC13) d: 1.19 (9H, s), 1. 32 (3H, t, J = 7.6Hz), 1.37 (3H, d, J = 6.3Hz), 2.75 (2H, q, J = 7.6Hz), 3.35 (3H, m), 4.28 (1H, m), 4.40 (1H, m), 5.78 (1H, d, J = 5.5Hz), 5.88 (1H, d, J = 5.5Hz), 7.08 (1H, s), 7.72 (1H, s).

Example 125 - - Acid (5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid a) (5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 4-Nitrobenzyl carboxylate In the same manner as in Example 5-a), (5R, 6S) -2- (7-cyanoimidazo [5, 1-b] thiazol-2-yl) -6- ( (IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 200-milligrams from 276 milligrams of (3R, 5R, 6S) -6- ((IR ) -1-hydroxyethyl) -2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 417 milligrams of 7-cyano-2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear magnetic resonance (DMSO-d6) d: 1.17 (3H, d, J = 6.3Hz), 3.47 (2H,), 3.54 (1H, dd, Jl = 6.0Hz, j2 = 3.0Hz), 4. 01 (1H, m), 4.27 (1H, m), 5.17 (1H, d, J = 5.0Hz), 5.43 (1H, d, J = 13.7Hz), 5.56 (1H, d, J = 13.7Hz), 7.76 (2H, d, J = 8.5Hz), , 25 (2H, d, J = 8.5Hz), 8.43 (1H, s), .51 (1H, s). MS (TSP): 511 (Mt + H). MS (FAB +): 370 (M + + 3), 368 (M + + 1). b) (5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 acid -carboxylic acid In the same manner as in Example 5-b), the header compound was obtained in a yield of 53.8 milligrams of (5R, 6S) -2- (7-cyanoimidazo [5, 1-b] thiazole-2) -yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.31 (3H, d, J = 6.4Hz), 3.27 (3H,), 3.51 (1H, dd, Jl = 5.8Hz, J2 = 2.8Hz), 4.26 (2H, m), 7.82 (1H, s), 8.13 (1H, s).

Example 126 (5R, 6S) -2- (7-Cyanoimidazo [5, lb] thiazol-2-yl) -6- (pivaloyloxymethyl) ((1R) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate De in the same manner as in Example 19, the header compound was obtained in a yield of 18.5 milligrams from 41.2 milligrams of the acid (5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-2-yl) -6- ((1R) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid. Nuclear Magnetic Resonance (CDC13) d: 1.23 (9H, s), 1.37 (3H, d, J = 6.3Hz), 3.34 (3H, m), 4.32 (2H, m), 5.90 (1H, d, J = 5.6 Hz), 6.02 (1H, d, J = 5.6Hz), 8.03 (1H, s), 8.29 (1H, s).

Example 127 (SS, 5R, 6S) -2- (7-ethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l- carbapen-2-em-3-carboxylate (internal salt) a) iodide of (ΔS, 5R, 6S) -2- (7-ethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -1-hydroxyethyl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 4-a), the iodide of (SS, 5R, 6S) -2- (7-ethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR ) -1-hydroxyethyl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl from 97.7 milligrams of (SS, 5R, 6S) -2- (7-ethylimidazo [5,1] -b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (DMSO-d6) d: 1.18 (3H, d, J = 6.3Hz), 1.22 (3H, d, J = 7.4Hz), 1.29 (3H, t, J = 7.6Hz), 2.88 (2H, t, J = 7.6Hz), 3.49 (1H, dd, Jl = 5.7Hz, j2 = 3.1Hz), 3.73 (1H, m), 3.98 (3H, s), 4.04 (1H, m), 4.39 (1H, dd, Jl = 10.1Hz, J2 = 3.1Hz), 5.18 (1H, d, J = 4.4Hz), 5.40 (1H, d, J = 13.9Hz), 5.53 (1H, d, J = 13.9Hz), 7.73 (2H, d, J = 8.7Hz), 8.23 (2H, d, J = 8.7Hz), 8.61 (1H, s), 9.51 (1H, s). b) (1S, 5R, 6S) -2- (7-ethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- ((IR) -l-hydroxyethyl) -l-methyl- l-carbapen-2-em-3-carboxylate (internal salt) In the same manner as in Example 4-b), the title compound was obtained in a yield of 50.6 milligrams of the whole amount of the iodide of (SS, 5R, 6S) -2- (7-ethyl-6-methylimidazo [5, 1-b] thiazolium-2-yl) -6- - ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl obtained above. Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1.22 (3H, d, J = 6.9Hz), 1.33 (6H, m), 2.82 (2H, c, J = 7.4Hz), 3.55 (2H, m ), 3.94 (3H, s), 4.27 (2H, m), 8.02 (1H, s), 9.05 (HH, s).

Example 128 Acid (5R, 6S) -2- (5,7-dimethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 -carboxylic a) (5R, 6S) -2- (5,7-dimethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2- 4-Nitrobenzyl em-3-carboxylate In the same manner as in Example 5-a), (5R, 6S) -2- (5,7-dimethylimidazo [5, 1-b] thiazole-2- was obtained il) - 6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl from 560 milligrams of (3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-oxo-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and 852 milligrams of 5,7-dimethyl-2- (tri-n-butylstannyl) imidazo [5, 1- b] thiazole. Nuclear Magnetic Resonance (DMSO-dβ) d: 1.17 (3H, d, J = 6.3Hz), 2.14 (3H, s), 2.46 (3H, s), 3.3-3.5 (3H, m), 4.01 (1H,) , 4.24 (1H, m), 5.16 (1H, d, J = 5.0Hz), 5.40 (1H, d, - J = 14.0Hz), 5.52 (1H, d, J = 14.0Hz), 7.75 (2H, d, J = 8.3Hz), 8.15 (1H, s), 8.24 (2H, d, J = 8.3Hz). b) Acid (5R, 6S) -2- (5,7-dimethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em -3-carboxylic acid In the same manner as in Example 5-b), the header compound was obtained in a yield of 105.2 milligrams from 269 milligrams of (5R, 6S) -2- (5,7-dimethylimidazo [ 5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D20) d (HOD = 4.80): 1.32 (3H, d, J = 6.2Hz), 2.33 (3H, s), 2.70 (3H, s), 3.30 (2H, m), 3.55 (1H, m), 4.30 (2H, m), 7.71 (1H, s).

Example 129 (5R, 6S) -2- (5,7-dimethylimidazo [5, lb] thiazol-2-yl) -6- ((1R) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate from pivaloyloxymethyl In the same manner as in Example 19, the title compound was obtained in a yield of 40.3 milligrams from 99.4 milligrams of acid (5R, 6S) -2- (5,7-Dimethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 carboxylic Nuclear magnetic resonance (CDC13) d: 1.23 (9H, s), 1. 37 (3H, d, J = 6.3Hz), 2.28 (3H, s), 2.57 (3H, s), 3.28 (3H, m), 4.27 (2H, m), 5.90 (1H, d, J = 5.6Hz ), 6.01 (1H, d, J = 5.6Hz), 8.02 (ÍH, s).

EXAMPLE 130 Acid (5R, 6S) -2- (7-formylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 -carboxylic a) (5R, 6S) -2- (7-formylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em- 3-Nitrobenzyl 3-carboxylate To a solution of 428 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-hydroxymethylimidazo [5, 1-b] thiazol-3-yl ) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 30 milliliters of dichloromethane were added 1.03 grams of manganese dioxide and the mixture was stirred at room temperature for 18 hours. The catalyst was stirred by filtration and the filtrate was concentrated under reduced pressure. The residue obtained in this way was elevated with diethyl ether to provide 202.8 milligrams of (5R, 6S) -2- (7-formylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) - 1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (CDC13) d: 1.32 (3H, d, J = 6.4Hz), 3.30-3.40 (4H, m), 4.21-4.36 (HH, m), 4.42 (1H, dt, - Jl = 9.6Hz, j2 = 3.0Hz), 5.14 (1H, d, J = 13.5Hz), 5.29 (1H, d, J = 13.5Hz), 7.40 (2H, d, J = 8.8Hz), 7.72 (1H , s), 8.09 (2H, d, J = 8.8Hz), 9.79 (1H, s). MS (TSP): 483 (M + + H). b) (5R, 6S) -2- (7-formylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 acid -carboxylic acid In the same manner as in Example 5-b) the title compound was obtained in a yield of 45.1 milligrams from 142.1 milligrams of (5R, 6S) -2- (7-formylimidazo [5, 1-b] ] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.27 (3H, d, J = 6.2Hz), 3.19-3.28 (HH, m), 3.43-3.53 (HH, m), 3.59-3.62 (HH, m), 4.25-4.32 (1H, m), 4.36-4.44 (ÍH, m), 7.34 (1H, s), 7.99 (1H, s), 9.58 (1H, s).

Example 131 (5R, 6S) -2- (7-formylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate from pivaloyloxymethyl In the same manner as in Example 19, the title compound was obtained in a yield of 8.2 milligrams from 31.4 milligrams of the (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2 acid. - (7-formylimidazo [5, lb] thiazol-3-yl) - - - l-methyl-l-carbapen-2-em-3-carboxylic acid and 0.016 milligram of pivaloyloxymethyl iodide. Nuclear Magnetic Resonance (CDC13) d: 1.19 (9H, s), 1.38 (3H, d, J = 6.3Hz), 2.33 (1H, br.s, s), 3.37-3.41 (3H, m), 4.28-4.34 (ÍH, m), 4.42-4.50 (ÍH, m), 5.77 (1H, d, J = 5.5Hz), 5.88 (1H, d, J = 5.5Hz), 7.27 (1H, s), 7.84 (1H, s).

Example 132 (5R, 6S) -2- (7-ethyl-6-methylimidazo [5, 1-b] thiazolium-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em- 3-carboxylate (inner salt) In the same manner as in Example 14, the header compound was obtained in a yield of 2.2 milligrams from 73.9 milligrams of (5R, 6S) -2- (7-ethyli idazo [5 , 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -1-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D2O) d (HOD = 4.80 ppm): 1. 32 (3H, d, J = 6.4Hz), 1.40 (3H, t, J = 7.4Hz), 2.90 (2H, q, J = 7.4Hz), 3.24 (ÍH, dd, Jl = 17.1Hz, J2 = 9.8 Hz), 3.45 (ÍH, dd, Jl = 17.1Hz, J2 = 8.7Hz), 3.60 (1H, m), 3.96 (3H, s), 4.29 (1H, m), 4.39 (1H, m), 7.44 (1H, s), 8.84 (1H, s).

Example 133 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5, 6, 7-trimethylimidazo [5, 1-b] thiazolium-2-yl) -l-carbapen-2- em-3-carboxylate (internal salt) a) iodide of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5,6, 7-trimethylimidazo [5, 1-b] thiazolium- 2-yl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 4-a), except that the reaction was carried out for four days, it was obtained ( 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (56, 7-trimethylimidazo [5, 1-b] thiazolium-2-yl) -l-carbapen-2-em-3-carboxylic acid 4-nitrobenzyl ester from 86.1 milligrams of (5R, 6S) -2 iodide - (5, 7-dimethylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (DMSO-d6) d: 1.17 (3H, d, J = 6.5Hz), 2.44 (3H, s), 2.84 (3H, s), 3.50 (2H, m), 3.60 (1H, m), 3.80 (3H, s), 4.04 (1H, m), 4.33 (1H, m), 5.20 (1H, br.s), 5.44 (1H, d, J = 13.6Hz), 5.56 (1H, d, J = 13.6Hz), 7.76 (2H, d, J = 8.4Hz), 8.26 (2H, d, J = 8.4Hz), 8.55 (1H, s). b) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (5, 6, 7-trimethylimidazo [5, 1-b] thiazolium-2-yl) -l-carbapen-2- em-3-carboxylate) inner salt In the same manner as in Example 4-b), the header compound was obtained in a yield of 19.8 milligrams of the total amount of (5R, 6S) -6- ((IR) -1- - hydroxyethyl) -2- (5, 6, 7-methylimidazo [5, 1-b] thiazolium-2-yl) -1-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D2?) D (HOD = 4.80 ppm): 1.28 (3H, d, J = 6.4Hz), 2.34 (3H, s), 2.73 (3H, s), 3.25 (2H, m), 3.46 ( 1H, m), 3.76 (3H, s), 4.22 (2H, m), 7.73 (1H, s).

Example 134 (1S, 5R, 6S) -2- (7-Acetylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2- sodium em-3-carboxylate a) (SS, 5R, 6S) -2- [7- (1-t-butyldimethylsilyloxy) ethylimidazo [5, 1-b] thiazol-2-yl] -6- ((IR) 1-hydroxyethyl) -methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl (diastereomeric mixture of about 1: 1) In the same manner as in Example 5-a), (S, 5R, 6S) -2- [7- (1-t-butyldimethylsilyloxy) ethylimidazo [5, 1-b] thiazol-2-yl] -6- ((IR) -1-hydroxyethyl) -methyl-1-carbapen- 4-Nitrobenzyl 2-em-3-carboxylate (diastereomeric mixture of about 1: 1) in a yield of 332 milligrams from 575 milligrams of (IR, 3R, 5R, 6S) -6- ((IR) -1 -hydroxyethyl) -methyl-2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 1.09 grams of 7- (1-t-butyldimethylsilyloxy (ethyl-2- (tri-n-butylstannyl) imidazo [5,1] -b] thiazole (racemic mixture).

- Nuclear Magnetic Resonance (CDC13) d: 0.09 (1.5H, s), 0.11 (1.5H, s), 0.13 (3H, s), 0.95 (4.5H, s), 0.96 (4.5H, s), 1.30 (3H , d, J = 7.2Hz), 1.39 (3H, d, J = 6.3Hz), 1.50 (3H, m), 3.36 (1H, dd, Jl = 6.5Hz, J2 = 2.7HZ), 3.45 (1H, m ), 4.34 (2H, m), 5.09 (1H, m), 5.26 (1H, d, J = 13.7Hz), 5.51 (HI, d, J = 13.7Hz), 7.67 (2H, d, J = 8.8Hz) ), 7.93 (1H, s), 8.23 (2H, d, J = 8.8Hz), 8.32 (0.5, s), 8.32 (0.5H, s). b) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- [7- (1-hydroxy) ethylimidazo [5, 1-b] thiazol-2-yl] -1-methyl -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl (diastereomeric mixture of about 1: 1) _ To a solution of 332 milligrams of (1S, 5R, 6S) -2- [7- (1-t -butyldimethylsilyloxy) ethylimidazo [5, lb] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl (diastereoisomeric mixture about 1: 1) in 3 milliliters of DMF and 1 milliliter of NMP were added 180 milligrams of ammonium hydrogen difluoride and the mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with 50 milliliters of ethyl acetate and 50 milliliters of aqueous saline solution and adjusted to a pH of 8 with a solution of sodium hydrogen carbonate until a pH of 8.0. The organic layer was separated and the aqueous layer was further extracted with ethyl acetate. The combined organic layer was washed twice with an aqueous saline solution, dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue obtained in this way was purified by column chromatography on silica gel (dichloromethane: methanol = 20: 1) to provide 80.5 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) - 2- [7- (1-hydroxy) ethylimidazo [5, 1-b] thiazol-2-yl] -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl (diastereoisomeric mixture of about 1 : 1) . Nuclear Magnetic Resonance (CDC13) d: 1.30 (3H, d, J = 7.2Hz), 1.40 (3H, d, J = 6.3Hz), 1.61 (3H, d, J = 6.5Hz), 3.36 (1H, dd, Jl = 6.3Hz, J2 = 2.6HZ), 3.46 (1H, m), 4.34 (2H, m), 5.07 (1H, q, J = 6.5Hz), 5.27 (ÍH, d, J = 13.7Hz), 5.52 (1H, d, J = 13.7Hz), 7.68 (2H, d, J = 8.6Hz), 7.96 (1H, s), 8.24 (2H, d, J = 8.6Hz), 8.32 (ÍH, s). c) (1S, 5R, 6S) -2- (7-acetylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- 2-Em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 74-a), (SS, 5R, 6S) -2- (7-acetylimidazo [5, 1-b] thiazole-2 was obtained -yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl from 197 milligrams of (1S, 5R, 6S) -6 - ((IR) -1-hydroxyethyl) -2- [7- (1-hydroxy) ethylimidazo [5, 1-b] thiazol-2-yl] -l-methyl-l-carbapen-2-em-3 4-Nitrobenzyl carboxylate (diastereomeric mixture of about 1: 1).

Nuclear magnetic resonance (CDC13) d: 1.31 (3H, d, J = 7.4Hz), 1.40 (3H, d, J = 6.2Hz), 2.61 (3H, s), 3.40 (1H, dd, Jl = 6.6Hz, J2 = 2.9Hz), 3.52 (ÍH, m ), 4.32 (ÍH, m), 4.42 (ÍH, dd, Jl = 9.7Hz, J2 = 2.9Hz), 5.27 (ÍH, d, J = 13.5Hz), 5.52 (ÍH, d, J = 13.5Hz), 7.67 (2H, d, J = 8.5Hz), 8.01 (1H, s), 8.22 (2H, d, J = 8.5Hz), 8.50 (1H, s). d) (1S, 5R, 6S) -2- (7-acetylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-1-carbapen- Sodium 2-em-3-carboxylate To a solution of 98.2 milligrams of (1S, 5R, 6S) -2- (7-acetylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in 5.8 milliliters of THF and 5.8 milliliters of a 1/15 M sodium phosphate stabilizer (ph of 6.6) 98 milligrams of 10 percent Pd-C were added. The reactor was purged with hydrogen and the reaction mixture was stirred at room temperature for 2 hours. The catalyst was removed by filtration through Celite and washed with water. The filtrate was adjusted to a pH of 6.5 with an aqueous sodium hydrogen carbonate solution, washed with ethyl acetate and the aqueous layer was purified by column chromatography on DIAION HP-20 (20 percent methanol in water ) to provide 38.1 milligrams of the header compound.

Nuclear Magnetic Resonance (D2O) d (HOD = 4.80 ppm): 1.20 (3H, d, J = 7.2Hz), 1.33 (3H, d, J = 6.4Hz), 2.45 (3H, s), 3.50 (HI, dd) , Jl = 6.1Hz, J2 = 2.5Hz), 3.57 (HH, m), 4.28 (HH, m), 4.33 (1H, dd, Jl = 9.3Hz, J2 = 2.5Hz), 7.92 (1H, s), 8.05 (1H, s).

Example 135 (1S, 5R, 6S) -2- (7-Acetylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1-hydroxyethyl) -l-methyl-l-carbapen-2- pivaloyloxymethyl em-3-carboxylate To a solution of 38.1 milligrams of (1S, 5R, 6S) -2- (7-acetylimidazo [5, 1-b] thiazol-2-yl) -6- ((IR) -1 sodium hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate in 3 milliliters of DMF was added 0.021 milliliter of pivaloyloxymethyl iodide under an argon atmosphere at -30 ° C, and the mixture was stirred for 1.5 hours. The reaction mixture was diluted with 20 milliliters of ethyl acetate and washed with 20 milliliters of a semi-saturated aqueous saline solution. The organic layer was dried through anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to a volume of 3 milliliters. The residue obtained in this way was purified by silica gel column chromatography (dichloromethane: methanol = 20: 1) and in Sephadex LH-20 (chloroform: methanol = 1: 1) in this sequence to provide 35.8 milligrams of the header. Nuclear magnetic resonance (CDC13) d: 1.20 (9H, s), 1. 29 (3H, d, J = 7.3Hz), 1.37 (3H, d, J = 6.3Hz), 2.62 (3H, s), 3. 36 (1H, dd, Jl = 6.5Hz, J2 = 2.9HZ), 3.50 (1H, m), 4.30 (1H, m), 4.40 (ÍH, dd, J? = 9.7Hz, J2 = 2.9Hz), 5.87 (ÍH, d, J = 5.6Hz), 5.99 (1H, d, J = 5.6Hz), 8.05 (1H, s), 8.51 (1H, s).

Example 136 Acid (5R, 6S) -2- (7-Acetylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid a) (5R, 6S) -2- [7- (l-butyldimethylsilyloxy) ethylimidazo [5, 1-b] thiazol-3-yl] -6- ((IR) -1-hydroxyethyl) -l-carbapen-2 4-Nitrobenzyl-ene-3-carboxylate (diastereomeric mixture of about 1: 1) In the same manner as in Example 5-a), (5R, 6S) -2- [7- (1-t- butyldimethylsilyloxy) ethylimidazo [5, 1-b] thiazol-3-yl] -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl (diastereoisomeric mixture of about 1 : 1) in a yield of 1.26 grams of (3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 3.00 grams of 7 - (L-butyldimethylsilyloxy) ethyl-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole (racemic mixture). Nuclear Magnetic Resonance (CDC13) d: 0.10 (3H, s), 0.13 (3H, s), 0.96 (9H, s), 1.39 (3H, d, J = 6.3Hz), 1.47 (1.5H, d, J = 6.2Hz), 1.49 (1.5H, d, J = 6.2Hz), 3.36 (3H, m), 4.31 (1H, m), 4.42 (1H, m), 5.08 (1H, q, J = 6.2Hz), 5.23 (1H, d, J = 13.5Hz), 5.37 (1H, d, J = 13.5Hz), 7.04 (0.5H, s), 7.05 (0.5H, s), 7.43 (1H, d, J = 8.2Hz ), 7.45 (1H, d, J = 8.2Hz), 7.66 (1H, s), 8.18 (2H, d, J = 8.2Hz). b) (5R, 6S) -6- ((lR) -l-hydroxyethyl) -2- [7- (l-hydroxy) ethylimidazo [5, 1-b] thiazol-3-yl] -l-carbapen-2 4-Nitrobenzyl-ene-3-carboxylate (diastereoisomeric mixture of about 1: 1) In the same manner as in Example 134-b), except that the reaction was carried out for four days, (5R, 6S was obtained ) -6- ((IR) -1-hydroxyethyl) -2- [7- (1-hydroxy) ethylimidazo [5, 1-b] iazol-3-yl] -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl (diastereomeric mixture of about 1: 1) in a yield of 245 milligrams from 1.03 grams of (5R, 6S) -2- [7- (1-t-butyldimethylsilyloxy) ethylimidazo [5, 1-b] ] thiazol-3-yl] -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl (diastereomeric mixture of about 1: 1).

Nuclear Magnetic Resonance (CDC13) d: 1.41 (3H, d, J = 6.3Hz), 1.59 (3H, d, J = 6.3Hz), 3.36 (3H, m), 4.32 (H, m), 4.43 (1H, m), 5.03 (ÍH, q, J = 6.3Hz)), 5.21 (1H, d, J = 13.5Hz), 5.36 (1H, d, J = 13.5Hz), 7.03 (1H, s), 7.44 (2H) , d, J = 8.8Hz), 7.67 (1H, s), 8.18 (2H, d, J = 8.8Hz). c) (5R, 6S) -2- (7-acetylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 4-nitrobenzyl carboxylate In the same manner as in Example 74-a), (5R, 6S) -2- (7-acetylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 was obtained 4-nitrobenzylcarboxylate in a yield of 58.6 milligrams from 262 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- [7-1-hydroxy) ethylimidazo [5,1] -b] thiazol-3-yl] -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl (diastereoisomeric mixture of about 1: 1). Nuclear Magnetic Resonance (CDC13) d: 1.40 (3H, d, J = 6.3Hz), 2.57 (3H, s), 3.41 (3H, m), 4.33 (1H, m), 4.48 (1H, m), 5.20 ( 1H, d, J = 13.4Hz), 5.36 (1H, d, J = 13.4Hz), 7.23 (1H, s), 7.46 (2H, d, J = 8.8Hz), 7.79 (1H, s), 8.16 ( 2H, d, J = 8.8Hz). d) (5R, 6S) -2- (7-acetylimidazo [5, 1-b] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -l-carbapen-2-em-3 acid -carboxylic acid In the same manner as in Example 5-b), the header compound was obtained in a yield of 6.6 milligrams from 58.6 milligrams of (5R, 6S) -2- (7-acetylimidazo [5, lb] thiazol-3-yl) -6- ((IR) -1-hydroxyethyl) -1-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1. 32 (3H, d, J = 6.3Hz), 2.56 (3H, s), 3.25 (1H, m), 3.48 (1H, m), 3.6K1H, m), 4.29 (1H, m), 4.40 (1H, m), 7.31 (1H, s), 7.96 (1H, s).

Example 137 (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxyiminomethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2- em-3-carboxylate (geometric isomer derived from a raw material that is a high polar oxime isomer) a) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxyiminomethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl (geometric isomer derived from a raw material which is a high polar oxime isomer) In the same manner as in Example 5-a), (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxyiminomethylimidazo [5, 1-b] thiazole was obtained -2-yl) -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl (geometric isomer derived from a raw material that is a high polar oxime isomer) in a yield of 275 milligrams from of 362 milligrams of (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2-oxo-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and 564 milligrams of 7-methoxyiminomethyl-2- (tri-n-butyltin nil) imidazo [5, 1-b] thiazole (geometric isomer derived from a raw material that is a high polar oxime isomer) described in Preparation 14. Nuclear magnetic resonance (CDC13) d: 1.30 (3H, d, J = 7.4Hz), 1.39 (3H, d, J = 6.2Hz), 3.38 (ÍH, dd, J? = 6.3Hz, J2 = 2.8HZ), 3.50 (1H, m), 4.00 (3H, s), 4.33 ( 1H, m), 4.40 (1H, dd, Jl = 9.6Hz, J2 = 2.8Hz), 5.26 (1H, d, J = 13.7Hz), 5.52 (ÍH, d, J = 13.7Hz), 7.46 (1H, s), 7.66 (2H, d, J = 8.8Hz), 7.96 (1H, s), 8.21 (2H, d, J = 8.8Hz), 8.33 (1H, s). b) (1S, 5R, 6S) -6- ((lR) -l-hydroxyethyl) -2- (7-methoxyiminomethylimidazo [5, 1-b] thiazol-2-yl) -1-methyl-1-carbapen- 2-em-3-carboxylate (geometric isomer derived from a raw material that is a high polar oxime isomer) In the same manner as in Example 5-b), the header compound was obtained in a yield of 14.7 milligrams a from 225 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxyiminomethylimidazo [5, 1-b] thiazol-2-yl) -methyl-l-carbapen -2-em-3-carboxylate of 4-nitrobenzyl (geometric isomer derived from a raw material which is a high polar oxime isomer). Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.19 (3H, d, J = 7.0Hz), 1.32 (3H, d, J = 6.5Hz), 3.47 (2H, m), 3.88 (3H, s) ), 4.28 (2H, m), 7.23 (1H, s), 7.80 (1H, s), 8.13 (1H, S).

Example 138 Acid (1S, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] - carbapen-2-em-3-carboxylic a) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- [7- (N-methylcarbamoyl) imidazo [5,1] -b] thiazol-2-yl] -carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), (S, 5R, 6S) -6- (( IR) -1-hydroxyethyl) -l-methyl-2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 201 milligrams from 205 milligrams of acid (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2-oxo-l-carbapen-2-em -3-carboxylate and 299 milligrams of 7- (N-methylcarbamoyl) -2- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear magnetic resonance (CD13) d: 1.30 (3H, d, J = 7.3Hz), 1.40 (3H, d, J = 6.2Hz), 1.72 (1H, m), 3.01 (3H, d, J = 5.0Hz) , 3.38-3.41 (ÍH, m), 3.45-3.54 (lH m), 4.28-4.37 (1H, m), 4.40-4.45 (lH, m), 5.27 (1H, d, J = 13.7Hz), 5.51 ( 1H, d, J = 13.7Hz), 7.66 (2H, d, J = 8.9Hz), 7.92 (ÍH, s), 8.23 (2H, d, J = 8.9Hz), 8.48 (1H, s).

MS (APCI): 526 (M + + H). b) acid (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -1-methyl-2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl) ] -carbapen-2-em-3-carboxylic acid. _. In the same manner as in Example 5-b), the header compound was obtained in a yield of 61 milligrams from 116.2 milligrams of acid (IS, 5R, 6S) -6- ((IR) -1-hydroxyethyl ) -l-methyl-2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (D20) d (HOD = 4.80 ppm): 1.22 (3H, d, J = 6.9Hz), 1.31 (3H, d, J = 6.0Hz), 2.91 (3H, s), 3.48-3.61 (2H) , m), 4.23-4.32 (2H, m), 4.32 (2H, m), 7.92 (1H, s), 8.04 (ÍH, s).

Example 139 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -carbapen Pivaloyloxymethyl 2-em-3-carboxylate In the same manner as in Example 19, the compound of the heading was obtained in a yield of 23.0 milligrams from 41.8 milligrams of (1S, 5R, 6S) -6- ( (IR) -1-hydroxyethyl) -l-methyl-2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -l-carbapen-2-em-3-carboxylate and 0.023 milliliter of pivaloyloxymethyl iodide. Nuclear Magnetic Resonance (CDC13) d: 1.17 (9H, s), 1.28 (3H, d, J = 7.4Hz), 1.37 (3H, d, J = 6.3Hz), 2.26-2.29 (HI, m), 3.01 ( 3H, d, J = 5.0Hz), 3.32-3.38 (HH, m), 3.45-3.54 (HH, m), 4.26-4.33 (1H, s), 4.38-4.41 (HH, m), 5.87 (1H, d, J = 5.6Hz), 5.99 (1H, d, J = 5.6Hz), 6.88-6.93 (ÍH, m), 7.97 (1H, s), 8.5 (1H, s). MS (TSP): 505 (M + + H).

Example 140 (1S, 5R, 6S) -2- [7- (N, N-dimethylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -6- ((1) -1-hydroxyethyl) -methyl-1 -carbapen-2-em-3-carboxylate sodium A solution of 725 milligrams of (SS, 5R, 6S) -6- ((IR) -hydroxyethyl) -l-methyl-2-oxo-l-carbapenam-3- 4-Nitrobenzyl carboxylate in 6 milliliters of anhydrous acetonitrile was cooled to -25 ° C under an argon atmosphere. To the solution was added diisopropylethylamine (520 milligrams) followed by 636 milligrams of anhydrous trifluoromethanesulfonic acid, and the mixture was stirred for 30 to 40 minutes and then diluted with 50 milliliters of ethyl acetate and 20 milliliters of an aqueous semi-saline solution. -Saturated, stirred and separated. The organic layer was washed with a mixture of 15 milliliters of a semi-saturated aqueous saline solution and 2 milliliters of 1 N hydrochloric acid and with a mixture of 15 milliliters of the semi-saturated aqueous saline solution and 1 milliliter of a carbonate solution. of saturated sodium hydrogen, was stirred, dried through anhydrous magnesium sulfate and the solvent was removed under reduced pressure. After concentrating the solvent to a volume of about 1 milliliter, it was diluted with 6 milliliters of NMP, and the mixture was concentrated again. To the concentrated material was added a solution of a mixture of 7- (N, N-dimethylcarbamoyl) -2- (tri-n-butylstannyl) imidazothiazole and 7- (N, N-dimethylcarbamoyl) -3- (tri-n-butylstannyl) ) imidazothiazole (ca. 1: 1) which is described in Preparation 22 in 3 milliliters of NMP, followed by 55 milligrams of tris (dibincilidenaketone) dipalladium (0), 56 milligrams of tri-2-furylphosphine and 560 milligrams of zinc was sufficiently dried and the mixture was stirred under the argon atmosphere at room temperature for 1 hour and at 55 ° C for an additional 2 hours. The reaction mixture was diluted with 100 milliliters of ethyl acetate, washed with 50 milliliters of water and three or four times with 50 milliliters of the semi-saturated aqueous saline solution and dried through anhydrous magnesium sulfate and the solvent it was removed under reduced pressure. The residue - obtained in this way was purified by column chromatography on silica gel (dichloromethane: methanol = 98: 2-95: 5) to provide 699 milligrams of a mixture of (1S, 5R, 6S) -2- [7- (N , N-dimethylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -6- ((1) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate from 4- Nitrobenzyl and (SS, 5R, 6S) -2- [7- (N, N-dimethylcarbamoyl) imidazo [5, lb] thiazol-2-yl] -6- ((1) -1-hydroxyethyl) -l-methyl 4-Nitrobenzyl-l-carbapen-2-em-3-carboxylate (ca. 1: 1). To a solution of the mixture in 28.5 milliliters of THF and 28.5 milliliters of a 1/15 M phosphate stabilizer (pH of 6.8), 600 milligrams of 10 percent Pd-C were added and the reactor was purged with hydrogen. The reaction mixture was stirred vigorously at room temperature for 2 hours and filtered through Celite, and the Celite was washed with 50 milliliters of THF / water (1: 1). The combined filtrate was washed with 80 milliliters of ethyl acetate and the solvent was concentrated under reduced pressure. The residue obtained in this way was purified by desalting by column chromatography on DIAION HP-20 (water-water: acetonitrile = 9: 1)., and then by chromatography separation of preparation column in COSMOSEAL 5C18-MS (20 X 250 mm) (acetonitrile: water = 1: 1), and the first fractions between those containing two primary components were collected, concentrated under pressure reduced and lyophilized to provide the header compound in a yield of 156 milligrams. Nuclear Magnetic Resonance (D20) 5 (HOD = 4.80 ppm): 1.21 (3H, d, J = 7.1Hz), 1.32 (3H, d, J = 6.3Hz), 2.9-3.7 (7H, m), 3.49 (1H , dd, Jl = 6.3Hz, J2 = 2.5HZ), 4.27 (2H, m), 7.89 (1H, s), 8.01 (ÍH, s).

Example 141 (1S, 5R, 6S) -2- [7- (N, N-dimethylcarbamoyl) imidazo [5, lb] thiazol-2-yl] -6- ((1) -1-hydroxyethyl) -l-methyl-1 -carbapen-2-em-3-pivaloyloxymethyl carboxylate To a solution of 50 milligrams of (SS, 5R, 6S) -2- [7- (N, N-dimethylcarbamoyl) imidazo [5, lb] thiazol-2-yl ] -6- ((1) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate sodium in 0.7 milliliter of DMF was added 5.0 milligrams of sodium hydrogencarbonate and the mixture was cooled to -30 ° C under the argon atmosphere. The reaction mixture was added with 43 milligrams of pivaloyloxymethyl iodide, stirred for 1 hour, extracted with 20 milliliters of ethyl acetate and the organic layer was washed with 12 milliliters of a semi-saturated aqueous salt solution, dried through anhydrous magnesium sulfate and concentrated under reduced pressure to a volume of about 1 - - milliliter. The residue obtained in this way was purified by column chromatography on silica gel (dichloromethane: methanol = 95: 5) to provide 55 milligrams of the header compound. Nuclear Magnetic Resonance (CDC13) 5: 1.18 (9H, s) 1.26 (3H, d, J = 7.3Hz), 1.35 (3H, d, J = 6.3Hz), 3.0-3.8 (6H, m), 3.32 (1H , dd, Jl = 7.1Hz, J2 = 2.8Hz), 3.46 (1H, m), 4.23 (1H, m), 4.37 (ÍH, dd, J? = 9.8Hz, J2 = 2.8HZ), 5.85 (1H, d, J = 5.6Hz), 5.96 (1H, d, J = 5.6Hz), 8.0 (1H, s), 8.50 (1H, s).

Example 142 (SS, 5R, 6S) -2- [7- (N, N-dimethylcarbamoyl) imidazo [5, 1-b] thiazol-3-ylj -6- ((1) -1-hydroxyethyl) -l-methyl- sodium l-carbapen-2-em-3-carboxylate In the chromatography of preparation in Example 140, the second fractions among those containing two primary components were collected, concentrated under reduced pressure and lyophilized to provide the title compound in a yield of 154 milligrams. Nuclear Magnetic Resonance (CDC13) d: 1.14 (3H, d, J = 7.1Hz), 1.31 (3H, d, J = 6.4Hz), 3.0-3.7 (8H, m), 4.3 (1H, m), 4.41 ( ÍH, dd, Jl = 9.9Hz, J2 = 3.0Hz), 7.25 (1H, s), 8.01 (ÍH, s).

- Example 143 (SS, 5R, 6S) -2- [7- (N, N-dimethylcarbamoyl) imidazo [5, 1-b] thiazol-3-yl] -6- ((1) -1-hydroxyethyl) -l-methyl pivaloyloxymethyl-l-carbapen-2-em-3-carboxylate To a solution of 50 milligrams of. (SS, 5R, 6S) -2- [7- (N, N-dimethylcarbamoyl) imidazo [5, 1-b] sodium thiazol-3-yl] -6- ((1) -1-hydroxyethyl) -l-methyl-l-carbapen-2-em-3-carboxylate in 0.7 milliliter of DMF was added 5.0 milligrams of hydrogen carbonate of sodium and the mixture was cooled to -30 ° C under an argon atmosphere. After addition of 43 milligrams of pivaloyloxymethyl iodide, the mixture was stirred for 1 hour, extracted with 20 milliliters of ethyl acetate and the organic layer was washed with 12 milliliters of a semi-saturated aqueous saline solution, dried The solution was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to a volume of about 1 milliliter. The residue obtained in this way was purified by column chromatography on silica gel (dichloromethane: methanol = 95: 5) to provide 48 milligrams of the title compound. Nuclear Magnetic Resonance (CDC13) d: 1.14 (9H, s), 1.12 (3H, d, J = 7.6Hz), 1.34 (3H, d, J = 6.2Hz), 3.0-3.8 (6H, m), 3.42 ( 1H, dd, J? = 6.5Hz, J2 = 3.2HZ), 3.6 (1H, m), 4.28 (1H, m), - - 4. 48 (HH, dd, J? = 10.4Hz, J2 = 3.2HZ), 5.70 (HH, d, J = 5.6Hz), 5.83 (1H, d, J = 5.6Hz), 7.18 (1H, s), 7.74 (lH, s).

Example 144 Acid (5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-3-yl] -6- ((1) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid a) (5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-3-yl] -6- ((1) -1-hydroxyethyl) -l-carbapen-2-em-3 4-Nitrobenzyl carboxylate In the same manner as in Example 5-a), (5R, 6S) -2- (7-cyanoimidazo [5, 1-b] thiazol-3-yl] -6- (( 1) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 29.7 milligrams from 46 milligrams of (3R, 5R, 6S) -6- ((1) - 1-hydroxyethyl) -2-oxo-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl and 69.6 milligrams of 7-cyano-3- (tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Nuclear magnetic resonance (CDC13) d: 1.41 (3H, d, J = 6.3Hz), 3.39 (3H, m), 4.33 (1H, m), 4.47 (1H, m), 5.23 (1H, d, J = 13.3 ), 5.39 (1H, d, J = 13.3Hz), 7.18 (1H, s), 7.54 (2H, d, J = 8.4Hz), 7.69 (1H, s), 8.22 (2H, d, J = 8.4Hz ). b) (5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-3-yl] -6- ((1) -1-hydroxyethyl) -l-carbapen-2-em-3 acid -carboxylic acid In the same manner as in Example 5-b), the header compound was obtained in a yield of 35.4 milligrams from 124 milligrams of (5R, 6S) -2- (7-cyanoimidazo [5, 1-] b] thiazol-3-yl] -6- ((1) -1-hydroxyethyl) -1-carbapen-2-em-3-carboxylate of 4-nitrobenzyl, nuclear magnetic resonance (D2O) d (HOD = 4.0 ppm) : 1.32 (3H, d, J = 6.4Hz), 3.23 (ÍH, dd, J? = 17.3Hz, J2 = 9.9Hz), 3.46 (1H, dd, Jl = 17.3Hz, j2 = 8.3Hz), 3.60 ( 1H, dd, Jl = 6.0Hz, J2 = 2.9Hz), 4.28 (1H, m), 4.39 (1H,), 7.27 (1H, s), 7.98 (1H, s).

Example 145 (5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-3-yl] -6- ((1) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylate from pivaloyloxymethyl In the same manner as in Example 19, the header compound was obtained in a yield of 23.2 milligrams from 31.1 milligrams of the acid (5R, 6S) -2- (7-Cyanoimidazo [5, 1-b] thiazol-3-yl] -6- ((1) -1-hydroxyethyl) -l-carbapen-2-em-3-carboxylic acid. Nuclear Magnetic Resonance (CDC13) d: 1.20 (9H, s), 1.38 (3H, d, J = 6.3Hz), 3.38 (3H, d, J = 5.6Hz), 7.20 (1H, s), 7.76 (1H, s).

- Example 146 Acid (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- [7- (N-methylcarba oil) imidazo [5, 1-b] thiazol-2-yl] -l-carbapen-2 -em-3-carboxylic acid a) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl In the same manner as in Example 5-a), (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2 was obtained - [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl in a yield of 217.6 milligrams from 264.3 milligrams of (3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2-oxo-carbapenam-3-carboxylate of 4-nitrobenzyl and 379.2 milligrams of 7- (N-methylcarbamoyl) -2- ( tri-n-butylstannyl) imidazo [5, 1-b] thiazole. Resonance | nuclear magnetic (CDC13) d: 1.41 (3H, d, J = 6.3Hz), 3.01 (3H, d, J = 5.0Hz), 3.32-3.40 (3H, m), 4.30-4.40 (3H,), 5.32 ( ÍH, d, J? = 13.8Hz), 5.54 (ÍH, d, J = 13.8Hz), 6.86 (1H, br.s, s), 7.69 (2H, d, J = 8.4Hz), 7.92 (1H, s), 8.25 (2H, d, J = 8.4Hz), 8.49 (1H, s). MS (TSP): 512 (M + + H). b) (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -l-carbapen- 2-em-3-carboxylic In the same manner as in Example 5-b), the title compound was obtained in a yield of 61 milligrams from 116.2 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl. Nuclear Magnetic Resonance (D2?) D (HOD = 4.80 ppm): 1.30 (3H, d, J = 6.5Hz), 2.90 (3H, s), 3.15-3.21 (2H, m), 3.42-3.48 (1H,) 4.18-4.30 (2H, m), 7.65- (lH, s), 7.93 (1H, s).

Example 147 (5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -l-carbapen-2-em Pivaloyloxymethyl carboxylate In the same manner as in Example 19, the title compound was obtained in a yield of 23.0 milligrams from 41.8 milligrams of (5R, 6S) -6- ((IR) -1-hydroxyethyl ) -2- [7- (N-methylcarbamoyl) imidazo [5, 1-b] thiazol-2-yl] -l-carbapen-2-em-3-carboxylate and "0.023 milliliter of pivaloyloxymethyl iodide." Nuclear Magnetic Resonance (CDC13) d: 1.22 (9H, s), 1.37 (3H, d, J = 6.3Hz), 1.18 (ÍH, br.s, s), 3.01 (3H, d, J = 5.1Hz), 3.29-3.37 (3H, m), 4.26-4.38 (2H, m), 5.90 (1H, d, J = 5.6Hz), 6.01 (1H, d, J = 5.6Hz), 6.89 (1H, br.s, s), 7.95 (1H, s), 8.58 (ÍH, s). 3 MS (FAB): 491 (M + H) Example 148 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxyiminomethylimidazo [5, 1-b] thiazol-2-yl] -1-methyl-1-carbapen-2 -em-3-carboxylate sodium (geometric isomer derived from a raw material that is a low polar oxime isomer) a) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- ( 7-methoxyiminomethylimidazo [5, 1-b] thiazol-2-yl] -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl (geometric isomer derived from a raw material which is an isomer of oxime low polar) - In the same manner as in Example 5-a), (ΔS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxyiminoethylimidazo [5, 1- b] thiazol-2-yl] -1-methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl (geometric isomer derived from a raw material which is a low polar oxime isomer) in a yield of 252 milligrams from 452 milligrams of (IR, 3R, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2-oxo-l-carbapenam-3-carboxylate of 4-nitrobenzyl and 704 milligrams of 7-methoxyiminomethyl-2- (tri- n-butylstannyl) imidazo [5, 1-b] thiazole which is described in Preparation 15 (geometric isomer derived from a raw material which is a low polar oxime isomer). Nuclear magnetic resonance (CDC13) d: 1.32 (3H, d, J = 7.2Hz), 1.39 (3H, d, J = 6.1), 3.38 (ÍH, dd, J? = 6.4Hz, J2 = 2.8Hz), 3.52 (1H, m), 3.96 (3H, s ), 4.33 (1H, m), 4.40 (1H, dd, Jl = 9.6Hz, J2 = 2.8HZ), 5.28 (IH, d, J = 13.7Hz), 5.53 (IH, d, J = 13.7Hz), 7.67 (2H, d, J = 8.2Hz), 8.03 (1H, s), 8.22 (1H, s), 8.23 (2H, d, J = 8.2Hz), 8.44 (1H, s). b) (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxyiminomethylimidazo [5, 1-b] thiazol-2-yl] -1-methyl-1-carbapen- Sodium 2-em-3-carboxylate (geometric isomer derived from a raw material which is a low polar oxime isomer) In the same manner as in Example 134-d), the header compound was obtained in a yield of 90. 8 milligrams from 252 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxyiminomethylimidazo [5, 1-b] thiazol-2-yl] -l- methyl-l-carbapen-2-em-3-carboxylate of 4-nitrobenzyl (geometric isomer derived from a raw material that is a low polar oxime isomer) Nuclear magnetic resonance (D20) d (HOD = 4.80 ppm): 1.22 (3H, d, J = 6.9Hz), 1.33 (3H, d, J = 6.3Hz), 3.53 (2H, m), 3.93 (3H, s), 4.30 (2H, m), 7.85 (1H, s ), 8.05 (1H, s).

Example 149 (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxyiminomethylimidazo [5, 1-b] thiazol-2-yl] -1-methyl-1-carbapen- Pivaloyloxymethyl 2-em-3-carboxylate (geometric isomer derived from a raw material which is a low polar oxime isomer) In the same manner as in Example 135, the heading compound was obtained in a yield of 96.2 milligrams from of 105 milligrams of (SS, 5R, 6S) -6- ((IR) -1-hydroxyethyl) -2- (7-methoxyiminomethylimidazo [5, 1-b] thiazol-2-yl] -l-methyl-l- sodium carbapen-2-em-3-carboxylate (geometric isomer derived from a raw material that is a low polar oxime isomer) Nuclear magnetic resonance (CDC13) d: 1.20 (9H, s), 1.30 (3H, d, J = 7.2Hz), 1.37 (3H, d, J = 6.2Hz), 3.34 (ÍH, dd, J? = 6.3Hz, J2 = 2.7Hz), 3.49 (1H, m), 3.97 (3H, s), 4.30 (1H, m), 4.37 (ÍH, dd, J? = 9.8Hz, J2 = 2.7HZ), 5.88 (1H, d, J = 5.6Hz), 6.00 (1H, d, J = 5.6Hz), 8.07 (1H, s), 8.23 (1H, s), 8.44 (1H, s) The structures of the compounds in the Examples ant cited above will be illustrated below. In this regard, * represents in bond with position 2 in the carbapenem ring and POM represents a pivaloyloxymethyl group 1.2 CH3 * H H H - H 3 CH3 * H H H - POM 4 CH3 * H H H CH3 - CH3 H * H H - H 6 CH3 H * H H - POM 7 CH3 H * H H CH3 - 8 H * H H H - H 9 CH3 * CH3 H H - H CH3 * CH3 H H - POM 12 H H * H H - H 13 H H * H H - POM 14 H H * H H CHg - H * H H H CHg - 16 CH3 * H H H CH2CONH2 - 17 CH3 *. H CH3 H - H 19 CH3 * H CH3 H - POM CH3 * H H C 1 - H 22 H CH3 * H H - H 23 CH3 * H H C 1 CH3 / 24 H * H H H - POM R R R R4 R 'R R H H CHg H H 26 H * H CH3 H POM 27 CH, * H H CH Na 28 CHj * H H CH3 - POM H * H CHg H CH, 31 CH * H 3 CH ^ NHCHO H H 32 CH; * H i CHgNHCHO H POM 3 »CH; H CHgNHCHO H CH, 34 CH, H CH2OH H H CH. * H CH2OH H POM 36 CH * CH2OH H H - H 37 CH H * 3 H CH3 - H 38 H * H H. CHg - Na 41 CH. H CH2OH H CHg 42 H * H H CHg CHg R R R R R R 49 CH3 * H H CH2NHCHO CHg 50 CHg H H * H - POM 52 CHg * H H H - CH-OC (0) CH3 53 CHg * H H - H - CH (CHg) OC (0) CHg * 54 CHg * H H H - CH2OC (0) - V ~ 55 CH3 * H H H - CH (CHg) OC (0) OCH2C 56 CHq * H H H - CH (CHg) OC (0) OCH (C 61 CHg * H H H C H (C Hg) O C (O) O C H2 ~ 62 CHg * H "H H - - R R R R R R 63 CH, H H H CH 20 C (0) 0 65 CH, H H H 68 CHg * H H H CH2OCCO) 0- < ~ 69 CH, H H H CH (CH 2 CHg) 0 C (0) 0- 70 CH3 * H CONH2 H H 72 H H H * H K 73 H H H * H POM 74 CHg * H CHO H H 76 * CH 3 H H CH 2 OH H 79 CHg H H H * CH, "" 80 H * H H C 1 Na - RRRRRRR 81 H * H CONH2 H - H 82 H * H CONHg H - POM 83 CH3 * H CHO H CH3 - 84 CHg HHH * - POM 85 CHg * HH CHgOH - POM 86 H * HHC 1 CHg - 87 H * HHC 1 - POM 88 H * HHH CH2CONH2 - 90 CHg * HH CHgNHCHO - Na 91 H * H * HH - CH, 0'C (0) CHg 92 HH * HH - CH (CH3) OC (0) CHg 93 H H * H H - CH 2 OC (0 - ^ ~ 94 H H * H H CH (CHg) OC (0) OCH 95 H H * H H CH (CH) OC (0) OCH 96 H H * H H CH (CHg) OC (0) 0- R R R R R R 102 H H * H CH2NHCHO POM 103 H H * H CONH2 H ' 104 H H * H CONH2 POM 106 H H * H CH2OH Na 107 CHg * H H CHO Na 108 CHg * H H * CHO POM 109 CH3 * H H CONH, H 110 CHg * H H CONH2 POM 111 CHg * H H CH2OCHg Na 113 H H * H CHgOCHg Na 114 H H * H CHgOCHg POM 115 H H * H CHgOH POM 116 CHg * H H CN H 117 CHg * H H CN POM 118 CHg * H H CH2CHg H 119 CHg * H H CH2CH3 # POM 120 H H * CONH2 H H 121 H * H H CH2CHg H 123 H H * H CHgCHg H 124 H H * H CHgCHg POM 125 H * H H CN H R1 R2 R3 R4 R5 R6 R 126 H * H H CN - POM 128 H * H CHg CHg - H 129 H * H CH3 CHg - POM 130 H H * H CHO - H 131 H H * H CHO - POM 132 H H * H tHgCHg CHg - 133 H * H CH3 CHg CHg - 134 CHg * H H C (0) CHg - Na 135 CHg * H H C (0) CHg - POM 136 H H * H C (0) CHg - H 137 CHg * H H CH = N0CHg - H 138 CHg * H H C (0) NHCHg - H 139 CHg * H H C (0) NHCHg - POM 140 CHg * H H C (0) NCCHg) 2 - Na 141 CHg * H H C (0) N (CHg) 2 - POM 142 CHg H * H C (0) N (CHg) 2 - Na 143 CHg H * H C (0) N (CHg) 2 - POM 144 H H * H CN - H 145 H H * H CN '- POM 146 H * H H C (0) NHCH 3 - H 147 H * H H C (0) NHCHg - POM 148 CHg * H H CH-NOCHg - N a * 149 CH, * H H CH-NOCH, - POM - - Preparation Example 1: injection The compound of Example 1 is aseptically distributed in a small bottle in an amount of 1000 milligrams (concentration) Preparation Example 2: capsule Compound of Example 3 250 parts (concentration) Lactose 60 parts (concentration) Magnesium stearate 5 parts (concentration) The components were mixed homogeneously and filled into a capsule in an amount of 250 milligrams (concentration) / capsule. Preparation example 3: soft capsule for rectal dosing Olive oil 160 parts (concentration) Polyoxyethylene lauryl ether 10 parts (concentration) Sodium hexametanoate 5 parts (concentration The compound of Example 3 in a 25 part amount (concentration) was added to and mixed with the base consisting of the components, and filled into a soft capsule for rectal dosing in an amount of 250. milligrams (concentration) / capsule Test 1: anti-microbial activities The minimum inhibitory concentrations (MIC, μg / ml) of the compounds according to the present invention with respect to several pathogenic bacteria was measured according to the method described in CHEMOTHERAPY , volume 16, Number 1, 99, 1968. The culture medium for measurement was the agar-N sensitivity disc + 5 percent horse blood and the quantity of the inoculants was 10 CU / milliliter. in the following table: Organism Example Example Example Compound Compound 1 4 8 AB S. aureus 209P JC-1 < 0.025 < 0.025 < 0.025 < 0.025 < 0.025 S. aureus M126 * .3.13 3.13 6.25 25 6.25 S. epidermis ATCC14990 < 0.025 < 0.025 0.05 < 0.025 0.05 E. hirae ATCC8043 0.39 0.78 0.78 0.78 1.56 E. faecalis W-73 0.20 0.10 0.39 0.78 3.13 S. pneumoniae PRC9 ** 0.10 0.05 0.20 0.20 0.39 B. catarrhalis W-0506 < 0.025 < 0.025 < 0.025 < 0.025 < 0.025 H. Influenzae PRC2 < 0.025 0.05 0.05 0.78 0.10 H. Influenzae PRC44 0.39 0.39 0.78 12.5 0.78 E. coli NIHJ JC-2 0.10 < 0.025 0.10 0.10 0.05 K. pneumoniae PCI602 0.10 0.05 0.05 0.20 0.10 P. vulgaris GN7919 0.05 0.10 0.10 0.10 0.10 C. freundii GN346 1.56 0.10 0.20 0.20 0.10 In the table, *: methicillin hyperresistant strain (MRSA); **: penicillin hyperresistant strain (PRSP); Compound A: imipenem; Compound B: acid iodide (IR, 5S, 6S) -6- ((IR) -1-hydroxyethyl) -l-methyl-2- [(3S, 5S) -5- (6-methylimidazo [5, 1- b] thiazolium-2-yl) methylpyrrolidin-3-yl] thiocarbapen-2-em-3-carboxycyl. As evident from the test results described above, the compounds according to the present invention have strong antimicrobial activities against MRSA, PRSP, enterococci, influenza, as well as various pathogenic bacteria, including ß-lactamase-producing bacteria. Test 2: Stability against DHP-I The stabilities of the compounds according to the present invention against porcine and mouse renal dehydropeptidases were measured by the following method. (1) Preparation of DHP-1 from kidney acetone powders of various animals. Kidney acetone powder, Type II Porcine (Sigma, Lot 33H7225, 1.5 grams) were suspended in a 50 mM Tris stabilizer. HCl (pH 7.0) containing percent butanol and the mixture was stirred at 5 ° C for 48 hours. Dialysis was carried out (cellulose tube 30/32; Viskase Sales Corp) with a stabilizer of 50 mM Tris-HCl (pH 7.0) in order to remove butanol to a level where there was no butanol odor. The dialyzed material was centrifuged at 10000g (KUBOTA 6800) for 20 minutes to provide a supernatant liquid such as a partially purified DHP-I, which was divided into portions and stored at -80 ° C. Also, a partially purified DHP-I was prepared from 1.5 grams of mouse (Lot 23F8105), and stored in the same manner as above. (2) Measurement of stabilities for different DHP-I. The compound according to the present invention as a basic pharmacist was diluted with sterile purified water to prepare a solution having a concentration of 2000 micrograms per milliliter. The solution of the compound according to the present invention having a concentration of 2000 micrograms per milliliter was added to the partially purified DHP-I of the animals described above in order to have a final concentration of 100 micrograms. (concentration) / milliliter. As a blank model was used 50 mM Tris-HCl (pH 7.0) instead of partially purified DHP-I from the animals. After the reaction at 37 ° C for 3 hours, a portion of the reaction mixture was extracted, diluted with the same amount of methanol to stop the reaction by cooling on ice. The reaction mixture was filtered through SUNLEP LCR13-LH, MILLIPORE), and subjected to HPLC (columan: CAPCELL PACK C18 SG120, SHISEIDO, UV detector, mobile phase: acetonitrile-10 mM aqueous acetic acid solution) to measure the residual amount (%) of partially purified DHP-I according to the following equation. maximum area of the sample residual amount (%) = X 100 maximum area of the blank model The residual amounts (%) of the compounds according to the present invention after 3 hours are shown below.

DHP-I Example 1 Example 4 Example 8 Compound A Compound C Swine 87 100 60 0.6 72 Mouse < 2.9 94 < 0.2 24 18 In the table, Compound A: imipenem; Compound B: meropenem. It will be understood from the aforementioned table that the compounds according to the present invention have great stabilities for porcine DHP-I and the carbapenem derivatives represented by the general formula (II) have great stabilities for both porcine DHP-I and of mouse. Test 3: Oral absorption capacity test The compound of Example 3 was orally administered to mice (ICR, male, n = 3) in an amount of 0.5 milligram (based on the weight of the compound of Example 1, from which the compound of Example 3) /O.2 milliliter / mouse as a suspension of 0.5% methylcellulose and then cilastatin was immediately administered subcutaneously in the same amount (due to the instability of the compound of Example 1 for mouse DHP-I, cilastatin as a DHP-I inhibitor was used in combination). As a result, the compound of Example 1 was excreted in the urine in an amount of 36 percent of the dose at 8 hours after administration. Test 4: acute toxicity test The compound of Example 1 was administered intravenously to the mice (ICR, male, n = 3) in an amount of 2000 milligrams per kilogram. As a result, all the animals survived.

Claims

R E I V I N D I C A C I O N S

1. A compound represented by the formula (I) or a pharmaceutically acceptable salt thereof: wherein: R1 represents a hydrogen or methyl, R2, R3 R4 and Rbf any of which represents the bond to position 2 in the carbapenem ring, and the other three of which may be the same or different, respectively represent hydrogen, halogen, nitro, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl group may be substituted by groups which are selected from the group consisting of halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, alkoxy lower, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-alkylamino lower) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and ary lo, lower cycloalkyl, in which one or more of the hydrogen atoms in the cycloalkyl group can be substituted by groups which are selected from the group consisting of lower alkyl, halogen, nitro, cyano, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and aryl, lower alkylthio, alkenyl of 2 to 4 carbon atoms, in where one or more of the hydrogen atoms in the alkenyl group can be substituted by groups which are selected from the group consisting of lower alkyl, halogen, nitro, cyano, lower cycloalkyl , lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl , (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and aryl, formyl, lower alkylcarbonyl , lower alkoxycarbonyl, lower alkylsulfonyl, lower arylsulfonyl, aminosulfonyl, arylcarbonyl, aryl, wherein one or more of the hydrogen atoms in the aryl group can be substituted by groups which are selected from the group consisting of lower alkyl, halogen, nitro , cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl , lower alkoxycarbonyl, formylamino, - - lower alkylcarbonylamino, carbamoyl, lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino , and (N, -di-lower alkylamino) sulfonylamino, carbamoyl, lower N-alkylcarbamoyl, N, -di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl, R ^ is not present, or represents lower alkyl, wherein one or more of the hydrogen atoms in the alkyl group can be substituted by groups which are selected from the group consisting of halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, alkylcarbonyl lower, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and aryl, lower cycloalkyl, wherein one or more of the hydrogen atoms in the cycloalkyl group may be substituted by groups which are selected from the group consisting of alkyl lower, halogen, nitro, cyano, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N -di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and aryl, or alkenyl of 2 to 4 carbon atoms, wherein one or more of the hydrogen atoms in the alkenyl group may be substituted by groups that are selected from the group consisting of lower alkyl , halogen, nitro, cyano, lower cycloalkyl, lower alkylthio, lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N , N-di-lower alkylaminocarbonyl, aminosulfonyl, (N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino and aryl, and R is not present, or represents hydrogen or a group that can be hydrolyzed metabolically in the body, as long as R6 is not present, R represents hydrogen or a group that can and hydrolyzed metabolically in the body, and when R ^ is present, R is not present, and the compound forms an internal salt.

2. A compound according to claim 1, wherein R is not present and R represents hydrogen or a group that can hydrolyze metabolically in the body.

3. A compound according to claim 2, wherein R represents hydrogen or methyl, R ^, R3, R4 and p5 ^ except that which represents the bond at position 2 in the carbapenem ring, which may be the same or different, and represents respectively hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl group may be substituted by groups which are selected from the group consisting of halogen, nitro, cyano, lower cycloalkyl, alkylthio - - lower, lower alkoxy, hydroxy, amino, lower N-alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, ( N-lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and aryl, formyl, lower alkylcarbonyl, alkoxycarbonyl lower, aminosulfonyl, carbamoyl, lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl.

4. A compound according to claim 3, wherein the lower alkyl is unsubstituted or is substituted by lower alkoxy, hydroxide or formylamino.

5. A compound according to any of claims 2 to 4, wherein R represents lower alkylcarbonyloxy lower alkyl, lower cycloalkylcarbonyloxy lower alkyl, lower alkyloxycarbonyloxy lower alkyl, cycloalkyloxycarbonyloxy lower lower alkyl, cycloalkylmethoxycarbonyloxy lower lower alkyl, haloxycarbonyloxy-alkyl lower, 2-oxo-5-lower alkyl-1,3-dioxolen-4-ylmethyl, 3-phthalidyl from which the aromatic ring may be substituted, or 2- (3-phthalidylidene) ethyl from which the aromatic ring may be substituted. - 6.

A compound according to claim 1, wherein R represents methyl, R2, represents the bond to position 2 in the carbapenem ring, and R3, R4 and R ^, which may be the same or different represent respectively hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl can be substituted by lower alkoxy, hydroxide, or formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl , N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl. Jl.

A compound according to claim 1, wherein R represents hydrogen, R2, represents the bond at position 2 on the carbapenem ring, and R3, R ^ and R5, which may be the same or different, respectively represent hydrogen, halogen , cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl may be substituted by lower alkoxy, hydroxide, or formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or - - hydroxyiminomethyl.

8. A compound according to claim 1, wherein R represents methyl, R3, represents the bond at position 2 on the carbapenem ring, and R2, R ^ and R5, which may be the same or different, represent respectively hydrogen , halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl may be substituted by lower alkoxy, hydroxide, or formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl.

9. A compound according to claim 1, wherein R represents hydrogen, - - R3 represents the bond to position 2 in the carbapenem ring, and R2, R ^ and R5, which may be the same or different, respectively represent hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl it can be substituted by lower alkoxy, hydroxide, or formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl.

10. A compound according to claim 1, wherein R represents hydrogen or methyl, R ^, represents the bond at position 2 on the carbapenem ring, and - - R2, R- R5, which may be the same as different, represent respectively hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms may be substituted by lower alkoxy, hydroxy or formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl , aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl.

11. A compound according to claim 1, wherein R represents hydrogen or methyl, R5, represents the bond to the 2-position in the carbapenem ring, and R2, R-R4, which may be the same or different represent respectively hydrogen, - - halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms can be substituted by lower alkoxy, hydroxide, or formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N- lower di-alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl.

12. A compound according to claim 1, wherein R is present, R is not present and the compound forms an internal salt.

13. A compound according to 2, where R represents hydrogen or methyl, and R2, R3, R ^, R5 and R except that which represents the bond at position 2 in the carbapenem ring, which may be the same or differently represents hydrogen, halogen, cyano, lower alkyl, respectively, wherein one or more of the hydrogen atoms in alkyl can be substituted by a group selected from the group consisting of halogen, nitro, cyano, lower cycloalkyl, lower alkylthio , lower alkoxy, hydroxy, amino, N-lower alkylamino, formyl, lower alkylcarbonyl, arylcarbonyl, carboxyl, lower alkoxycarbonyl, formylamino, lower alkylcarbonylamino, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, aminosulfonyl, (N lower alkylamino) sulfonyl, (N, N-di-lower alkylamino) sulfonyl, (N-lower alkylamino) sulfonylamino, aminosulfonylamino, (N, N-di-lower alkylamino) sulfonylamino, and aryl, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl.

14. A compound according to 2 3 4 5 claim 13, wherein R, R, R and R except that - which represents the bond to position 2 in the carbapenem ring, represents hydrogen, halogen, cyano, lower alkyl wherein one or more of the hydrogen atoms in the alkyl can be substituted by a group selected from the group consisting of alkoxy lower, hydroxy and formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl, and R represents lower alkyl which can be substituted by a A group selected from the group consisting of lower alkoxy, hydroxy, formylamino and carbamoyl.

15. A compound according to claim 12, wherein R, represents, methyl, 2 R, represents the bond to position 2 in the carbapenem ring, - 3 4 5 R, R and R which may be the same or different represent respectively hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl may be substituted by a group selected from the group consisting of of lower alkoxy, hydroxy and formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl, and R represents lower alkyl which can be substituted by a group that is selected from the group consisting of lower alkoxy, hydroxy, formylamino and carbamoyl.

16. A compound according to claim 12, wherein R represents hydrogen, 2 R represents the bond to position 2 in the carbapenem ring, 3 4 5 R, R and R which may be the same or different represent respectively hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl can be substituted by a group selected from the group consisting of lower alkoxy, hydroxy and formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl , aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl, and R represents lower alkyl which can be substituted by a group selected from the group consisting of lower alkoxy, hydroxy, formylamino and carbamoyl.

A compound according to claim 12, wherein R represents methyl, 3 R represents the bond at position 2 on the carbapenem ring, 2 4 5 R, R and R which may be the same or different represent hydrogen respectively , halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms can be substituted by a group selected from the group consisting of lower alkoxy, hydroxy and formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl , Lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl, and R represents lower alkyl which can be substituted by a group selected from the group consisting of lower alkoxy, hydroxy, formylamino and carbamoyl.

18. A compound according to claim 1, wherein R represents hydrogen, 3 R represents the bond at position 2 on the carbapenem ring, - 2 4 5 R, R and R which may be the same or different represent respectively hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl may be substituted by a group selected from the group consists of lower alkoxy, hydroxy and formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl, and 6R represents lower alkyl which can be Substitute by a group selected from the group consisting of lower alkoxy, hydroxy, formylamino and carbamoyl.

19. A compound according to claim 1, wherein R represents hydrogen or methyl, R represents the bond to position 2 in the carbapenem ring, 2 3 5 R, R and R which may be the same or different they represent respectively hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl can be substituted by a group selected from the group consisting of lower alkoxy, hydroxy and formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl, aminosulfonyl, carbamoyl, lower N-alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl, and R represents lower alkyl which may be substituted by a group selected from the group consisting of lower alkoxy , hydroxy, formylamino and carbamoyl.

20. A compound according to claim 12, wherein R represents hydrogen or methyl, R represents the bond to position 2 in the carbapenem ring, 2 3 4 R, R and R which may be the same or different represent respectively hydrogen, halogen, cyano, lower alkyl, wherein one or more of the hydrogen atoms in the alkyl can be substituted by a group selected from the group consisting of lower alkoxy, hydroxy and formylamino, formyl, lower alkylcarbonyl, lower alkoxycarbonyl , aminosulfonyl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl, or hydroxyiminomethyl, and R represents lower alkyl that can be substituted by a group selected from the group consisting of lower alkoxy, hydroxy , formylamino and carbamoyl.

21. A compound according to claim 2, wherein R or R represents the bond to position 2 in the carbapenem ring.

22. A compound according to claim 1, wherein R represents alkyl having one or two carbon atoms which can be substituted by carbamoyl, fluoro or hydroxy.

23. A compound according to claim 2, wherein R represents the bond to position 2 in the carbapenem ring, all of the R, R and R represent hydrogen, or 3 4 5 both R and R represent hydrogen and R represents a group selected from the group consisting of lower alkyl which can be substituted by formylamino or lower alkoxy, chloro, formyl, lower alkylcarbonyl, cyano, carbamoyl, N-lower alkylcarbamoyl and N, N-di-lower alkylaminocarbonyl .

24. A compound according to claim 2, wherein R represents the bond to the 3-position in the carbapenem ring, R represents methyl. - -

25. A compound according to claim 3, wherein R represents the bond in the 2-position 2 in the carbapenem ring, both R and R 5 represent hydrogen and R represents hydrogen or cyano.

26. A pharmaceutical composition comprising the compound according to any of claims 1 to 25, and a pharmacologically acceptable carrier.

27. A pharmaceutical composition according to claim 24, which is used as an antibacterial agent.

28. A method for the treatment of infectious diseases comprising administering the compound according to any of claims 1 to 25 to an animal, including humans.

29. The use of the compound according to any of claims 1 to 25, for preparing an antibacterial agent. -

30. The use of the conforming compound with any of claims 1 to 25, as an antibacterial agent. SUMMARY OF THE INVENTION The carbapenem derivatives represented by the following formula (I) are disclosed. These compounds have anti-bacterial and intense activities against bacteria, including Staphylococcus aureus resistant to methicillin,? Streptococcus pneumoniae resistant to penicillin, Enterococci, influenza, and ß-lactamase producing bacteria, and have great stabilities to DHP-1. where R ^ represents hydrogen or methylO, any of R2, R3, R4 or R5 represents the bond to position 2 on the carbapenem ring, and the remaining three respectively represent hydrogen, halogen, nitro, cyano, alkyl, cycloalkyl, alkylthio , alkenyl, formyl, alkylcarbonyl, alkoxycarbonyl, aminosulfonyl, arylcarbonyl, aryl, carbamoyl, N-lower alkylcarbamoyl, N, N-di-lower alkylaminocarbonyl, lower alkoxyiminomethyl or hydroxyiminomethyl, R ^ is not present, or represents alkyl, cycloalkyl or alkenyl and R is not present or represents hydrogen or a group that can be hydrolyzed metabolically in the body, as long as R ° is not present, R represents hydrogen or a group that can hydrolyze metabolically in the body, and when R ^ is present, R does not is present, and the compound forms an internal salt.