Method for producing nitrogen-containing heteroarylcarboxamide acetic acid derivative

A process for preparing a compound of formula [1(A)]:

• said process comprising:
• (i) reacting a compound of formula (a4):
• wherein Za2 is a hydroxy group or a substituent represented by formula:
• wherein P1 is a protecting group for hydroxy group,
• Za3 is a bromine atom, an iodine atom or a trifluoromethanesulfoxy group, with a compound of formula (a5):
• wherein Xa1 and Xa2 are each independently a hydrogen atom or an alkyl group, or alternatively, both of them bind to each other to form an alkylene group,
• in the presence or absence of a base, in the presence or absence of a palladium catalyst, in a solvent or in the absence of a solvent to prepare a compound of formula (a1-1-a):
• wherein, Za2 is the same as defined above:
• (ii) reacting the compound of formula (a1-1-a) with a compound of formula (2-1):
• wherein R1-1 is an optionally substituted alkyl group or a resin residue, or
• a salt thereof,
• and carbon monoxide in the presence or absence of a palladium catalyst, in the presence or absence of a ligand, in the presence or absence of a base, in a solvent or in the absence of a solvent to obtain a compound of formula (a3-1-a):
• wherein R1-1 and Za2 are the same defined above;
• and
• (iii) converting the compound of formula (a3-1-a) into the compound of formula [I(A)]

A process for preparing a compound of formula [I(A)]:

• said process comprising:
• (i) reacting a of compound of formula (a4-1):
• wherein Za2-1 is a substituent represented by formula:
• wherein P1 is a protecting group for a hydroxy group, and
• Za3 is a bromine atom, an iodine atom, or a trifluoromethanesulfoxy group, with a compound of formula (a5):
• wherein Xa1 and Xa2 are each independently a hydrogen atom, or an alkyl group, or alternatively both of them bind to each other to form an alkylene group,
• in the presence of absence of a base, in the presence of absence of a palladium catalyst, in a solvent or in the absence of a solvent, to prepare a compound of formula (a1-3-a)
• wherein Za2-1 is the same as defined above;
• (ii) converting the compound of formula (a1-3-a) into the compound of formula (a1-4-a):
• (iii) reacting the compound of formula (a1-4-a) with a compound of formula (2-1):
• wherein R1-1 is an optionally substituted alkyl group or a resin residue, or a salt thereof,
• and carbon monoxide
• in the presence or absence of a palladium catalyst, in the presence or absence of a ligand, in the presence or absence of a base, and in a solvent or in the absence of a solvent to prepare the compound of formula (a3-2-a):
• wherein R1-1 is the same as defined above;
• and
• (iv) converting the compound of formula (a3-2-a) into the compound of formula (I(A)):

A process for preparing a compound of formula (b3-1):

• wherein R1 is an optionally substituted alkyl group, a hydrogen atom, or a resin residue,
• R2 is a hydrogen atom, or an optionally substituted methyl group,
• R3 is a phenyl group which may be optionally substituted with halogen atom, a chlorine atom, a bromine atom, an iodine atom, or a trifluoromethanesulfoxy group, and
• R4 is a hydrogen atom, or alternatively,
• R3 and R4 bind to each other and combine together with the pyridine group to which they are adjacent to form an isoquinoline group which may be optionally substituted with phenyloxy group,
• said process comprising:
• (i) reacting a compound of formula (b1):
• wherein
• Z1 is a chlorine atom, a bromine atom, or an iodine atom,
• Zb2 is a chlorine atom, a bromine atom or an iodine atom, and
• R2, R3, and R4 are the same as defined above,
• with a compound of formula (2):
• wherein R1 is an optionally substituted alkyl group, a hydrogen atom, or a resin residue, or a salt thereof,
• and carbon monoxide,
• in the presence of a palladium catalyst, in the presence or absence of a ligand, in the presence of a base, in a solvent to obtain a compound of formula (b3):
• wherein the symbols are the same as defined above;
• and
• (ii) reacting the compound of formula (b3) with a compound of formula (b4):
• wherein Rb5 is an optionally substituted aryl group, or an optionally substituted alkyl group,
• in the presence of a palladium catalyst, in the presence or absence of a ligand, in the presence of a base, in a solvent to prepare a compound of formula (b3-1):
• wherein the symbols are the same as defined above.

A process for preparing a compound of formula (bI-1):

• wherein R2 is a hydrogen atom or an optionally substituted methyl group,
• Rb3-3 is a 3-chlorophenyl group, a chlorine atom, a bromine atom, an iodine atom, or a trifluoromethanesulfoxy group,
• Rb4-3 is a hydrogen atom, or alternatively
• Rb3-3 and Rb4-3 bind to each other and combine together with the pyridine group to which they are adjacent to form a 7-phenyloxy-isoquinoline group,
• said process comprising:
• (i) reacting a compound of formula (b1-2):
• wherein:
• Z1 is a chlorine atom, a bromine atom, or an iodine atom,
• Zb2 is a chlorine atom, a bromine atom, or an iodine atom, and
• R2, Rb3-3 and Rb4-3 are the same as defined above,
• or a compound of formula (2-1):
• wherein R1-1 is an optionally substituted alkyl group or a resin residue,
• or a salt thereof,
• and carbon monoxide,
• in the presence or absence of a palladium catalyst, in the presence or absence of a ligand, in the presence or absence of a base, and in a solvent or in the absence of a solvent to obtain a compound of formula (b3-4):
• wherein the symbols are the same as defined above, and
• (ii) reacting the compound of formula (b3-4) and a compound of formula (b4):
• wherein Rb5 is an optionally substituted aryl group or an optionally substituted alkyl group,
• in the presence of a palladium catalyst, in the presence or absence of a ligand, in the presence of a base, in a solvent to obtain a compound of formula (b3-5):
• wherein the symbols are the same as defined above;
• and
• (iii) converting the compound of formula (b3-5) into a compound of formula (bI-1):
• wherein the symbols are the same as defined above.

A compound of formula (a1-a):

• wherein:
• Z1 is a chlorine atom, a bromine atom, or an iodine atom, and
• Za2 is a hydroxy group, or a substituent represented by formula:
• wherein P1 is a protecting group for hydroxy group.