Uronium and immonium salts for peptide coupling

A salt, wherein the cation has the formula:

• 62
• or N-oxides thereof wherein
• A is an aryl group containing from 6 to 14 ring carbon atoms and up to a total of 20 carbon atoms or a heteroaryl ring wherein said heteroaryl ring is an oxygen, sulfur or nitrogen containing heteroaromatic having from 5 up to a total of 14 ring atoms and from 3 up to a total of 13 ring carbon atoms, and up to a total of 20 carbon atoms;
• said heteroaryl and aryl groups may be unsubstituted or substituted with an electron donating, an electron withdrawing group or lower alkyl;
• E is CR or N;
• R is H or lower alkyl
• R3 is a positively charged electron withdrawing group having the formula:
• 63
• wherein R10, R11, R12, R13, R14, R15 and R16 are independently hydrogen or lower alkyl which may be unsubstituted or substituted with an electron withdrawing or electron donating group or
• R10 and R12 taken together with the nitrogen atom to which they are attached and the carbon atom attached to both of said nitrogen atoms form a 5 or 6 membered nitrogen containing heterocyclic ring containing up to 4 carbon ring atoms;
• or R10 and R11 taken together with the nitrogen atom to which they are attached form a 5 or 6 membered nitrogen containing heterocyclic ring containing up to a total of 5 carbon ring atoms or R12 and R13 taken together with the nitrogen atom to which they are attached form a 5 or 6 membered nitrogen containing heterocyclic ring containing up to a total of 5 carbon ring atoms.

A salt formed from the reaction of R3Y and the salt of

• 87
• under substitution reaction conditions wherein
• Y is a leaving group;
• A is a cycloalkyl group containing 3 to 14 ring carbon atoms and up to a total of 20 carbon atoms, an oxygen, sulfur or nitrogen heterocyclic group wherein said heterocyclic group contains from 3 up to a total of 14 ring atoms and from 3 up to a total of 13 ring carbon atoms, and up to a total of 20 carbon atoms, said ring containing at least 1 heteroatom ring atom, said heteroatom present on the ring being selected from the group consisting of N and S, an aryl group containing 6 to 14 ring carbon atoms and up to a total of 20 carbon atoms or a nitrogen, oxygen or sufur heteroaryl group wherein said heteroaryl ring is an oxygen, sulfur, or nitrogen containing heteroaromatic ring containing 5 to 14 ring atoms and up to a total of 4 to 13 ring carbon atoms and 20 carbon atoms, said heteroatom being selected from the group consisting of N, O, and S, which cycloalkyl, heterocyclic, aryl and heteroaryl groups are unsubstituted or substituted by lower alkyl, an electron withdrawing group or an electron donating group.
• E is CR or N;
• R3 is a positively charged electron withdrawing group having the formula:
• 88
• wherein R10, R11, R12, R13, R14, R15 and R16 are independently hydrogen or lower alkyl which may be unsubstituted or substituted with an electron withdrawing or electron donating group or R10 and R12 taken together with the nitrogen atom to which they are attached and the carbon atom attached to both of said nitrogen atoms form a 5 or 6 membered nitrogen containing heterocyclic ring containing up to 4 carbon ring atoms;
• or R10 and R11 taken together with the nitrogen atom to which they are attached form a 5 or 6 membered nitrogen containing heterocyclic ring containing up to a total of 5 carbon ring atoms or R12 and R13 taken together with the nitrogen atom to which they are attached form a 5 or 6 membered nitrogen containing heterocyclic ring containing up to a total of 5 carbon ring atoms.

A salt wherein the cation has the formula:

• 92
• wherein
• Ra and Rb are independently hydrogen, an electron donating group or electron withdrawing group;
• E is CR or N;
• R is hydrogen or lower alkyl;
• R3 is a positively charged electron withdrawing group having the formula:
• 93
• wherein R10, R11, R12, R13, R14, R15 and R16 are independently hydrogen or lower alkyl which may be unsubstituted or substituted with an electron withdrawing or electron donating group or
• R10 and R12 taken together with the nitrogen atom to which they are attached and the carbon atom attached to both of said nitrogen atoms form a 5 or 6 membered nitrogen containing heterocyclic ring containing up to 4 carbon ring atoms;
• or R10and R11 taken together with the nitrogen atom to which they are attached form a 5 or 6 membered nitrogen containing heterocyclic ring containing up to a total of 5 carbon ring atoms or R12 and R13 taken together with the nitrogen atom to which they are attached form a 5 or 6 membered nitrogen containing heterocyclic ring containing up to a total of 5 carbon ring atoms.

A process for preparing a salt of the formula

• 94
• which comprises reacting a salt of
• 95
• and R3Y under substitution reaction conditions wherein
• Y is a leaving group;
• SB− is a counter anion;
• R3 is a positively charged electron withdrawing group having the formula:
• 96
• R10, R11, R12, R13, R14, R15, R16 are independently hydrogen or lower alkyl which may be unsubstituted or substituted with an electron withdrawing or electron donating group, or R10 and R12 taken together with the nitrogen atom to which they are attached and the carbon atom attached to the nitrogen atoms form a 5 or 6 membered nitrogen containing heterocyclic containing 3 or 4 ring carbon atoms, respectively or R10and R11 taken together with the nitrogen atom to which they are attached or R12 and R13 taken together with the nitrogen atom to which they are attached form a 5 or 6-membered heterocyclic ring containing up to 5 ring carbon atoms respectively or R14 and R15 taken together with the nitrogen atom to which they are attached form a 5 or 6-membered heterocyclic ring containing 4 or 5 ring carbon atoms, respectively or R14 taken together with the nitrogen to which it is attached and R16 taken together with the carbon atoms attached thereto form a 5 or 6 membered nitrogen containing heterocyclic ring, containing 4 or 5 ring carbon atoms, respectively;
• E is N or CR;
• R is hydrogen or lower alkyl;
• Ra and Rb are independently hydrogen, lower alkyl, an electron withdrawing group or electron donating group or Ra and Rb taken together with the carbon atoms to which they are attached form a cycloalkyl group containing 3 to 14 ring carbon atoms and up to a total of 20 carbon atoms, an oxygen, sulfur or nitrogen heterocyclic group wherein said heterocyclic group contains from 3 up to a total of 14 ring atoms and from 3 up to a total of 13 ring carbon atoms, and up to a total of 20 carbon atoms, said ring containing at least 1 heteroatom ring atom, said heteroatom present on the ring being selected from the group consisting of N and S, an aryl group containing 6 to 14 ring carbon atoms and up to a total of 20 carbon atoms or a nitrogen, oxygen or sufur heteroaryl group wherein said heteroaryl ring is an oxygen, sulfur, or nitrogen containing heteroaromatic ring containing 5 to 14 ring atoms and up to a total of 4 to 13 ring carbon atoms and 20 carbon atoms, said heteroatom being selected from the group consisting of N, O, and S, which cycloalkyl, heterocyclic, aryl and heteroaryl groups are unsubstituted or substituted by lower alkyl, an electron withdrawing group or an electron donating group.