Novel processes and intermediates for the preparation of soluble guanylate cyclase stimulators

A process of preparing a compound of Formula IA:

• comprising the step of:
• i) coupling an amide of formula (1′):
• with a pyrimidine compound of formula (2):
• in an aprotic organic solvent in the presence of a base, to form, after quenching with acid, an intermediate of formula (3′):
• ii) at a pH>5, optionally in the presence of added N,O-dimethylhydroxylamine or a salt thereof, allowing the mixture to react to form the compound of formula (4′):
• iii) condensing the compound of formula (4′) with a hydrazine of formula
• or a salt thereof, optionally in the presence of a base, to form a compound of Formula V:
• iv) de-methylating the compound of Formula V to form an alcohol compound of formula (9′):
• v) chlorinating the alcohol compound of formula (9′) with phosphoryl chloride to form a compound of Formula VI:
• vi) reacting an amine of formula (17):
• with the compound of Formula VI, optionally in the presence of a base, to yield the compound of Formula IA.

A process of preparing a compound of Formula IA:

• comprising the step of:
• i) coupling an amide of formula (1′):
• with a pyrimidine compound of formula (2):
• in an aprotic organic solvent in the presence of a base, to form, after quenching with an acid, an intermediate of formula (3′):
• ii) at a pH>5, optionally in the presence of added N,O-dimethylhydroxylamine or a salt (e.g. HCl salt) thereof, allowing the mixture to react to form the compound of formula (4′):
• iiia) condensing the compound of formula (4′) with hydrazine (e.g., hydrazine hydrate) to form the compound of formula (24′):
• iiib) alkylating intermediate of formula (24′) with an alkylating agent of formula (23A) to provide the compound of Formula V:
• iv) de-methylating the compound of Formula V to form an alcohol compound of formula (9′):
• v) chlorinating the alcohol compound of formula (9′) with phosphoryl chloride o form a compound of Formula VI:
• vi) reacting an amine of formula (17):
• with the compound of Formula VIA, optionally in the presence of a base, to yield the compound of Formula IA, wherein X is a leaving group selected from —Br, —I, —Cl, —F, and a sulfonate ester (e.g., mesylate, tosylate or triflate).