Novel mono- and di-fluorinated beozothiepine copmunds as inhibitors of apical sodium co-dependent bile acid transport (ASBT) and taurocholate uptake

A method for treating a hyprelipidemic condition in a subject comprising administering to said subject in need thereof a therapeutically effective amount of a compound of Formulas I-1 or I-2, wherein said Formulas I-1 and I-2 are represented by:

• 799
• or a pharmaceutically acceptable salt, solvate, or prodrug thereof
• wherein j is 0, 1 or 2;
• wherein m is 0, 1, 2, 3 or 4;
• wherein R2A and R2B are independently selected from the group consisting of hydrogen and hydrocarbyl;
• wherein R3A, R3B, R5A, and R5B are independently selected from the group consisting of hydrogen, alkyl;
• cycloalkyl;
• alkenyl;
• alkynyl;
• heterocyclyl;
• quaternary heterocyclyl, oxo;
• aryl-R5;
• —OR9;
• —NR9R10;
• —SR9;
• —S(O)R9;
• —SO2R9;
• and —SO3R9;
• wherein R9 and R10 are independently selected from the group consisting of hydrogen;
• hydrocarbyl;
• amino;
• and hydrocarbylamino;
• wherein R5 is selected from the group consisting of hydrogen;
• hydrocarbyl, heterocyclyl;
• quaternary heterocyclyl;
• —OR9;
• —SR9;
• —S(O)R9;
• —SO2R9;
• and —SO3R9;
• wherein when R5 is said cycloalkyl, aryl or heterocyclyl, said cycloalkyl, aryl or heterocyclyl are optionally substituted with —NH—X—R or —O—X—R
• wherein X is selected from the group consisting of —(C═O)s-alkyl-;
• —(C═O)s-alkyl-NH—;
• —(C═O)s-alkyl-O—;
• —(C═O)s-alkyl-(C═O)t;
• and a covalent bond, wherein s and t are independently 0 or 1;
• wherein R is selected from the group consisting of monosaccharides, disaccharides, and polysaccharides, wherein said monosaccharides, disaccharides, and polysaccharides are optionally protected with one or more sugar protecting groups;
• wherein R9 and R10 are as previously defined;
• wherein, when R5≠H, R5 is optionally substituted with one or more radicals independently selected from the group consisting of halogen;
• —NO2;
• —CN;
• oxo;
• hydrocarbyl;
• —OR13;
• —NR13R14;
• —SR13;
• —S(O)R13;
• —SO2R13;
• —SO3R13;
• —NR13OR14;
• —NR13NR14R15;
• —CO2R13;
• —OM;
• —SO2OM;
• —SO2NR13R14;
• —C(O)NR13R14;
• —C(O)OM;
• —COR13;
• —NR13C(O)R14;
• —NR13C(O)NR14R15;
• —NR13;
• —CO2R14;
• —OC(O)R13;
• —OC(O)NR13R14;
• —NR13SR14;
• —NR13SO2R14;
• —NR13SONR14R15;
• —NR13SO2NR14R15;
• —PR13R14;
• —P(O)R13R14;
• —P+R13R14R5A−;
• —P(OR13)OR14;
• —S+R13R14A−;
• and —N+R13R14R15A−;
• wherein R13, R14, and R15 are independently selected from the group consisting of hydrogen and hydrocarbyl;
• wherein A− is a pharmaceutically acceptable anion;
• wherein M is a pharmaceutically acceptable cation;
• wherein one or more R6 radicals are independently selected from the group consisting of hydrogen;
• halogen;
• —CN;
• —NO2;
• hydrocarbyl;
• —R5;
• —OR13;
• —NR13R14;
• —SR13;
• —S(O)R13;
• —S(O)2R13;
• —SO3R13;
• —S+R13R14A−;
• —NR13OR14;
• —NR13NR14R15;
• —OM;
• —SO2OM;
• —SO2NR13R14;
• —NR14C(O)R13;
• —C(O)OM;
• —S(O)NR13R14;
• —N+R13R14R15A-;
• —PR13R14;
• —P(O)R13R14;
• —P+R13R14R15A−;
• amino acid residue;
• peptide residue;
• polypeptide residue;
• and carbohydrate residue;
• wherein R13, R14, R15, A−, and M are as defined above;
• and
• wherein, in each instance, said hydrocarbyl may be optionally substituted with one or more groups comprising one or more heteroatoms, and wherein, in each instance, said hydrocarbyl optionally may have one or more carbon atoms replaced by one or more heteroatoms independently selected from the group consisting of oxygen, nitrogen, sulfur, phosphorus and combinations thereof.

A method of treating gallstones or a condition associated therewith in a subject comprising administering to said subject in need thereof a therapeutically effective amount of a compound of Formulas I-1 or I-2 represented by:

• 800
• or a pharmaceutically acceptable salt, solvate, or prodrug thereof
• wherein j is 0, 1 or 2;
• wherein m is 0, 1, 2, 3 or 4;
• wherein R2A and R2B are independently selected from the group consisting of hydrogen and hydrocarbyl;
• wherein R3A, R3B, R5A, and R5B are independently selected from the group consisting of hydrogen, alkyl;
• cycloalkyl;
• alkenyl;
• alkynyl;
• heterocyclyl;
• quaternary heterocyclyl, oxo;
• aryl-R5;
• —OR9;
• —NR9R10;
• —SR9;
• —S(O)R9;
• —SO2R9;
• and —SO3R9;
• wherein R9 and R10 are independently selected from the group consisting of hydrogen;
• hydrocarbyl;
• amino;
• and hydrocarbylamino;
• wherein R5 is selected from the group consisting of hydrogen;
• hydrocarbyl, heterocyclyl, quaternary heterocyclyl;
• —OR9;
• —SR9;
• —S(O)R9;
• —SO2R9;
• and —SO3R9;
• wherein when R5 is said cycloalkyl, aryl or heterocyclyl, said cycloalkyl, aryl or heterocyclyl are optionally substituted with —NH—X—R or —O—X—R
• wherein X is selected from the group consisting of —(C═O)s-alkyl-;
• (C═O)s-alkyl-NH—;
• —(C═O)s-alkyl-O—;
• —(C═O)s-alkyl-(C═O)t;
• and a covalent bond, wherein s and t are independently 0 or 1;
• wherein R is selected from the group consisting of monosaccharides, disaccharides, and polysaccharides, wherein said monosaccharides, disaccharides, and polysaccharides are optionally protected with one or more sugar protecting groups;
• wherein R9 and R10 are as previously defined;
• wherein, when R5≠H, R5 is optionally substituted with one or more radicals independently selected from the group consisting of halogen;
• —NO2;
• CN;
• oxo;
• hydrocarbyl;
• —OR13;
• —NR13R14;
• —SR13;
• —S(O)R13;
• —SO2R13;
• —SO3R13;
• —NR13OR14;
• —NR13NR14R15;
• —CO2R13;
• —OM;
• —SO2OM;
• —SO2NR13R14;
• —C(O)NR13R14;
• —C(O)OM;
• —COR13;
• —NR13C(O)R14;
• —NR13C(O)NR14R15;
• —NR13CO2R14;
• —OC(O)R13;
• —OC(O)NR13R14;
• —NR13SOR14;
• —NR13SO2R14;
• —NR13SONR14R15;
• —NR13SO2NR14R15;
• —PR13R14;
• —P(O)R13R14;
• —P+R13R14R15A−;
• —P(OR13)OR14;
• —S+R13R14A−;
• and —N+R13R14R15A−;
• wherein R13, R14, and R15 are independently selected from the group consisting of hydrogen and hydrocarbyl;
• wherein A− is a pharmaceutically acceptable anion;
• wherein M is a pharmaceutically acceptable cation;
• wherein one or more R6 radicals are independently selected from the group consisting of hydrogen;
• halogen;
• —CN;
• —NO2;
• hydrocarbyl;
• —R13;
• —OR13;
• —NR13R14;
• —SR13;
• —S(O)R13;
• —S(O)2R13;
• —SO2R13;
• —S+R13R14A−;
• —NR13OR14;
• —NR13R14R15;
• —OM;
• —SO2OM;
• —SO2NR13R14;
• —NR14C(O)R13;
• —C(O)OM;
• —S(O)NR13R14;
• —N+R13R14R5A-;
• —PR13R14;
• —P(O)R13R14;
• —P+R13R14R15A−;
• amino acid residue;
• peptide residue;
• polypeptide residue;
• and carbohydrate residue;
• wherein R13, R14, R15, A−, and M are as defined above;
• and
• wherein, in each instance, said hydrocarbyl may be optionally substituted with one or more groups comprising one or more heteroatoms, and wherein, in each instance, said hydrocarbyl optionally may have one or more carbon atoms replaced by one or more heteroatoms independently selected from the group consisting of oxygen, nitrogen, sulfur, phosphorus and combinations thereof.

A method for treating a hyperlipidemic condition in a subject comprising administering to said subject in need thereof a therapeutically effective amount of a compound of Formulas I-17 or I-18 represented by:

• 801
• or a pharmaceutically acceptable salt, solvate, or prodrug thereof
• wherein j is 0, 1 or 2;
• wherein m is 0, 1, 2, 3 or 4;
• wherein R2A and R2B are independently selected from the group consisting of hydrogen and hydrocarbyl;
• wherein R3A, R3B, R5A, and R5B are independently selected from the group consisting of hydrogen, alkyl;
• cycloalkyl;
• alkenyl;
• alkynyl;
• heterocyclyl;
• quaternary heterocyclyl, oxo;
• aryl-R5;
• —OR9;
• —NR9R10;
• —SR9;
• —S(O)R9;
• —SO2R9;
• and —SO3R9;
• wherein R9 and R10 are independently selected from the group consisting of hydrogen;
• hydrocarbyl;
• amino;
• and hydrocarbylamino;
• wherein R5 is selected from the group consisting of hydrogen;
• hydrocarbyl, heterocyclyl;
• quaternary heterocyclyl;
• —OR9;
• —SR9;
• —S(O)R9;
• —SO2R9;
• and —SO3R9;
• wherein when R5 is said cycloalkyl, aryl or heterocyclyl, said cycloalkyl, aryl or heterocyclyl are optionally substituted with —NH—X—R or —O—X—R;
• wherein X is selected from the group consisting of —(C═O)s-alkyl-;
• —(C═O)s-alkyl-NH—;
• —(C═O)s-alkyl-O—;
• —(C═O)s-alkyl-(C═O)t;
• and a covalent bond, wherein s and t are independently 0 or 1;
• wherein R is selected from the group consisting of monosaccharides, disaccharides, and polysaccharides, wherein said monosaccharides, disaccharides, and polysaccharides are optionally protected with one or more sugar protecting groups;
• wherein R9 and R10 are as previously defined;
• wherein, when R5≠H, R5 is optionally substituted with one or more radicals independently selected from the group consisting of halogen;
• —NO2;
• CN;
• oxo;
• hydrocarbyl;
• —OR13;
• —NR13R14;
• —SR13;
• —S(O)R13;
• —SO2R13;
• —SO3R13;
• —NR13OR14;
• —NR13NR14R15;
• —CO2R13;
• —OM;
• —SO2OM;
• —SO2NR13R14;
• —C(O)NR13R14;
• —C(O)OM;
• —COR13;
• —NR13C(O)R14;
• —NR13c(O)NR14R15;
• —NR13CO2R14;
• —OC(O)R13;
• —OC(O)NR13R14;
• —NR13SOR14;
• —NR13SO2R14;
• —NR13SONR14R15;
• —NR13SO2NR14R15;
• —PR13R14;
• —P(O)R13R14;
• —P+R13R14R15A−;
• —P(OR13)OR14;
• —S+R13R14A−;
• and —N+R13R14R15A−;
• wherein R13, R14, and R15 are independently selected from the group consisting of hydrogen and hydrocarbyl;
• wherein A− is a pharmaceutically acceptable anion;
• wherein M is a pharmaceutically acceptable cation;
• wherein one or more R6 radicals are independently selected from the group consisting of hydrogen;
• halogen;
• —CN;
• —NO2;
• hydrocarbyl;
• —R5;
• —OR13;
• —NR13R14;
• —SR13;
• —S(O)R13;
• —S(O)2R13;
• —SO3R13;
• —S+R13R14A−;
• —NR13OR14;
• —NR13NR14R15;
• —OM;
• —SO2OM;
• —SO2NR13R14;
• —NR14C(O)R13;
• —C(O)OM;
• —S(O)NR13R14;
• —N+R13R14R15A-;
• —PR13R14;
• —P(O)R13R14;
• —P+R13R14R15A−;
• amino acid residue;
• peptide residue;
• polypeptide residue;
• and carbohydrate residue;
• wherein R13, R14, R15, A−, and M are as defined above;
• and
• wherein, in each instance, said hydrocarbyl may be optionally substituted with one or more groups comprising one or more heteroatoms, and wherein, in each instance, said hydrocarbyl optionally may have one or more carbon atoms replaced by one or more heteroatoms independently selected from the group consisting of oxygen, nitrogen, sulfur, phosphorus and combinations thereof.

A method for treating gallstones or a condition associated therewith in a subject in need thereof, said method comprising administering a therapeutically effective amount of a compound of Formulas I-17 or I-18 represented by:

• 813
• or a pharmaceutically acceptable salt, solvate, or prodrug thereof
• wherein j is 0, 1 or 2;
• wherein m is 0, 1, 2, 3 or 4;
• wherein R2A and R2B are independently selected from the group consisting of hydrogen and hydrocarbyl;
• wherein R3A, R3B, R5A, and R5B are independently selected from the group consisting of hydrogen, alkyl;
• cycloalkyl;
• alkenyl;
• alkynyl;
• heterocyclyl;
• quaternary heterocyclyl, oxo;
• aryl-R5;
• —OR9;
• —NR9R10;
• —SR9;
• —S(O)R9;
• —SO2R9;
• and —SO3R9;
• wherein R9 and R10 are independently selected from the group consisting of hydrogen;
• hydrocarbyl;
• amino;
• and hydrocarbylamino;
• wherein R5 is selected from the group consisting of hydrogen;
• hydrocarbyl, heterocyclyl;
• quaternary heterocyclyl;
• —OR9;
• —SR9;
• —S(O)R9;
• —SO2R9;
• and —SO3R9;
• wherein when R5 is said cycloalkyl, aryl or heterocyclyl, said cycloalkyl, aryl or heterocyclyl are optionally substituted with —NH—X—R or —O—X—R;
• wherein X is selected from the group consisting of —(C═O)s-alkyl-;
• —(C═O)s-alkyl-NH—;
• —(C═O)s-alkyl-O—;
• —(C═O)s-alkyl-(C═O)t;
• and a covalent bond, wherein s and t are independently 0 or 1;
• wherein R is selected from the group consisting of monosaccharides, disaccharides, and polysaccharides, wherein said monosaccharides, disaccharides, and polysaccharides are optionally protected with one or more sugar protecting groups;
• wherein R9 and R10 are as previously defined;
• wherein, when R5≠H, R5 is optionally substituted with one or more radicals independently selected from the group consisting of halogen;
• —NO2;
• CN;
• oxo;
• hydrocarbyl;
• —OR13;
• —NR13R14;
• —SR13;
• —S(O)R13;
• —SO2R13;
• —SO3R13;
• —NR13OR14;
• —NR13NR14R15;
• —CO2R13;
• —OM;
• —SO2OM;
• —SO2NR13R14;
• —C(O)NR13R14;
• —C(O)OM;
• —COR13;
• —N13C(O)R14;
• —NR13C(O)NR14R15;
• —NR13CO2R14;
• —OC(O)R13;
• —OC(O)NR13R14;
• —NR13SOR14;
• —NR13SO2R14;
• —NR13SONR14R15;
• —NR13SO2NR14R15;
• —PR13R14;
• —P(O)R13R14;
• —P+R13R14R15A−;
• —P(OR13)OR14;
• —S+R13R14A−;
• and —N+R13R14R15A−;
• wherein R13, R14, and R15 are independently selected from the group consisting of hydrogen and hydrocarbyl;
• wherein A− is a pharmaceutically acceptable anion;
• wherein M is a pharmaceutically acceptable cation;
• wherein one or more R6 radicals are independently selected from the group consisting of hydrogen;
• halogen;
• —CN;
• —NO2;
• hydrocarbyl;
• —R13;
• —OR13;
• —NR13R14;
• —SR13;
• —S(O)R13;
• —S(OR13;
• —SO3R13;
• —S+R13R14A−;
• —NR13OR14;
• —NR13NR14R15;
• —OM;
• —SO2OM;
• —SO2NR13R14;
• —NR14C(O)R13;
• —C(O)OM;
• —S(O)NR13, R14;
• —N+R13R14R15A-;
• —PR13R14;
• —P(O)R13R14;
• —P+R13R14R15A−;
• amino acid residue;
• peptide residue;
• polypeptide residue;
• and carbohydrate residue;
• wherein R13, R14, R15, A−, and M are as defined above;
• and
• wherein, in each instance, said hydrocarbyl may be optionally substituted with one or more groups comprising one or more heteroatoms, and wherein, in each instance, said hydrocarbyl optionally may have one or more carbon atoms replaced by one or more heteroatoms independently selected from the group consisting of oxygen, nitrogen, sulfur, phosphorus and combinations thereof.

A method of forming a compound of the Formula I-1:

• 825
• or a pharmaceutically acceptable salt, solvate, or prodrug thereof
• wherein j is 0, 1 or 2;
• wherein m is 0, 1, 2, 3 or 4;
• wherein R2A and R2B are independently selected from the group consisting of hydrogen and hydrocarbyl;
• wherein R3A, R3B, R5A, and R5B are independently selected from the group consisting of hydrogen, alkyl;
• cycloalkyl;
• alkenyl;
• alkynyl;
• heterocyclyl;
• quaternary heterocyclyl, oxo;
• aryl-R5;
• —OR9;
• —NR9R10;
• —SR9;
• —S(O)R9;
• —SO2R9;
• and —SO3R9;
• wherein R9 and R10 are independently selected from the group consisting of hydrogen;
• hydrocarbyl;
• amino;
• and hydrocarbylamino;
• wherein R5 is selected from the group consisting of hydrogen;
• hydrocarbyl;
• heterocyclyl;
• quaternary heterocyclyl;
• —OR9;
• —SR9;
• —S(O)R9;
• —SO2R9;
• and —SO3R9;
• wherein when R5 is said cycloalkyl, aryl or heterocyclyl, said cycloalkyl, aryl or heterocyclyl are optionally substituted with —NH—X—R or —O—X—R;
• wherein X is selected from the group consisting of —(C═O)s-alkyl-;
• —(C═O)s-alkyl-NH—;
• —(C═O)s-alkyl-O—;
• —(C═O)s-alkyl-(C═O)t;
• and a covalent bond, wherein s and t are independently 0 or 1;
• wherein R is selected from the group consisting of monosaccharides, disaccharides, and polysaccharides, wherein said monosaccharides, disaccharides, and polysaccharides are optionally protected with one or more sugar protecting groups;
• wherein R9 and R10 are as previously defined;
• wherein, when R5≠H, R5 is optionally substituted with one or more radicals independently selected from the group consisting of halogen;
• —NO2;
• CN;
• oxo;
• hydrocarbyl;
• —OR13;
• —NR13R14;
• —SR13;
• —S(O)R13;
• —SO2R13;
• —SO3R13;
• —NR13OR14;
• —NR13NR14R15;
• —CO2R13;
• —OM;
• —SO2OM;
• —SO2NR13R14;
• —C(O)NR13R14;
• C(O)OM;
• —COR13;
• —NR13C(O)R14;
• —NR13C(O)N14R15;
• —NR13CO2R14;
• —OC(O)R13;
• —OC(O)NR13R14;
• —NR13SOR14;
• —NR13SO2R14;
• —NR13SONR14R15;
• —NR13SO2NR14R15;
• —PR13R14;
• —P(O)R13R14;
• —P+R13R14R15A−;
• —P(OR13)OR14;
• —S+R13R14A−;
• and —N+R13R14R15A−;
• wherein R13, R14, and R15 are independently selected from the group consisting of hydrogen and hydrocarbyl;
• wherein A− is a pharmaceutically acceptable anion;
• wherein M is a pharmaceutically acceptable cation;
• wherein one or more R6 radicals are independently selected from the group consisting of hydrogen;
• halogen;
• —CN;
• —NO2;
• hydrocarbyl;
• —R5;
• —OR13;
• —NR13R14;
• —SR13;
• —S(O)R13;
• —S(O)2R13;
• —SO3R13;
• —S+R13R14A−;
• —NR13OR14;
• —NR13NR14R15;
• —OM;
• —SO2OM;
• —SO2NR13R14;
• —NR14C(O)R13;
• —C(O)OM;
• —S(O)NR13R14;
• —N+R13R14R15A-;
• —PR13R14;
• —P(O)R13R14;
• —P+R13R14R15A−;
• amino acid residue;
• peptide residue;
• polypeptide residue;
• and carbohydrate residue;
• wherein R13, R14, R15, A−, and M are as defined above;
• and
• wherein, in each instance, said hydrocarbyl may be optionally substituted with one or more groups comprising one or more heteroatoms, and wherein, in each instance, said hydrocarbyl optionally may have one or more carbon atoms replaced by one or more heteroatoms independently selected from the group consisting of oxygen, nitrogen, sulfur, phosphorus and combinations thereof,
• said method comprising the steps of:
• (a) forming a compound of Formula S1-78c:
• 826
• wherein R2A, R2B, R3A, R3B, R5A, R5B, R6, m and j are as previously defined;
• and
• (b) treating said compound of Formula S1-78c with diethylaminosulfur trifluoride to form said compound of Formula I-1.

A method of forming a compound of Formula I-2:

• 827
• or a pharmaceutically acceptable salt, solvate, or prodrug thereof
• wherein j is 0, 1 or 2;
• wherein m is 0, 1, 2, 3 or 4;
• wherein R2A and R2B are independently selected from the group consisting of hydrogen and hydrocarbyl;
• wherein R3A, R3B, R5A, and R5B are independently selected from the group consisting of hydrogen, alkyl;
• cycloalkyl;
• alkenyl;
• alkynyl;
• heterocyclyl;
• quaternary heterocyclyl, oxo;
• aryl-R5;
• —OR9;
• —NR9R10;
• —SR9;
• —S(O)R9;
• —SO2R9;
• and —SO3R9;
• wherein R9 and R10 are independently selected from the group consisting of hydrogen;
• hydrocarbyl;
• amino;
• and hydrocarbylamino;
• wherein R5 is selected from the group consisting of hydrogen;
• hydrocarbyl;
• heterocyclyl;
• quaternary heterocyclyl;
• —OR9;
• —SR9;
• —S(O)R9;
• —SO2R9;
• and —SO3R9;
• wherein when R5 is said cycloalkyl, aryl or heterocyclyl, said cycloalkyl, aryl or heterocyclyl are optionally substituted with —NH—X—R or —O—X—R;
• wherein X is selected from the group consisting of —(C═O)s-alkyl-;
• —(C═O)s-alkyl-NH—;
• —(C═O)s-alkyl-O—;
• —(C═O)s-alkyl-(C═O)t;
• and a covalent bond, wherein s and t are independently 0 or 1;
• wherein R is selected from the group consisting of monosaccharides, disaccharides, and polysaccharides, wherein said monosaccharides, disaccharides, and polysaccharides are optionally protected with one or more sugar protecting groups;
• wherein R9 and R10 are as previously defined;
• wherein, when R5≠H, R5 is optionally substituted with one or more radicals independently selected from the group consisting of halogen;
• —NO2;
• CN;
• oxo;
• hydrocarbyl;
• —OR13;
• —NR13R14;
• —SR13;
• —S(O)R13;
• —SO2R13;
• —SO3R13;
• —NR13OR14;
• —NR13NR14R15;
• —CO2R13;
• —OM;
• —SO2OM;
• —SO2NR13R14;
• —C(O)NR13R14;
• —C(O)OM;
• —COR13;
• —NR13C(O)R14;
• —NR13C(O)NR14R15;
• —NR13CO2R14;
• —OC(O)R13;
• —OC(O)NR13R14;
• —NR13SOR14;
• —NR13SO2R14;
• —NR13SONR14R15;
• —NR13SO2NR14R15;
• —PR13R14;
• —P(O)R13R14;
• —P+R13R14R15A−;
• —P(OR13)OR14;
• —S+R13R14A−;
• and —N+R13R14R15A−;
• wherein R13, R14, and R15 are independently selected from the group consisting of hydrogen and hydrocarbyl;
• wherein A− is a pharmaceutically acceptable anion;
• wherein M is a pharmaceutically acceptable cation;
• wherein one or more R6 radicals are independently selected from the group consisting of hydrogen;
• halogen;
• —CN;
• —NO2;
• hydrocarbyl;
• —R5;
• —OR13;
• —NR13R14;
• —SR13;
• —S(O)R13;
• —S(O)2R13;
• —SO3R13;
• —S+R13R14A−;
• —NR13OR14;
• —NR13R14R15;
• —OM;
• —SO2OM;
• —SO2NR13R14;
• —NR14C(O)R13;
• —C(O)OM;
• —S(O)NR13R14;
• —N+R13R14R15A-;
• —PR13R14;
• —P(O)R13R14;
• —P+R13R14R5A−;
• amino acid residue;
• peptide residue;
• polypeptide residue;
• and carbohydrate residue;
• wherein R13, R14, R15, A−, and M are as defined above;
• and
• wherein, in each instance, said hydrocarbyl may be optionally substituted with one or more groups comprising one or more heteroatoms, and wherein, in each instance, said hydrocarbyl optionally may have one or more carbon atoms replaced by one or more heteroatoms independently selected from the group consisting of oxygen, nitrogen, sulfur, phosphorus and combinations thereof,
• said method comprising the steps of:
• (a) forming a compound of Formula S1-78a:
• 828
• wherein R2A, R2B, R3A, R3B, R5A, R5B, R6, m and j are as previously defined;
• and
• (b) treating said compound of Formula S1-78a with diethylaminosulfur trifluoride to form said compound of Formula I-2.