Intermediates useful for the preparation of saxagliptin

A process for the preparation of compounds of formula (VI),

• wherein
• X is an oxygen atom or a NR1 group;
• R is a CONH2 group, a COOR2 group or a CN group;
• R1 is a hydrogen atom, a hydroxy group, an OR3 group, or an optionally substituted benzyl group;
• R2 is a linear or branched C1-10 alkyl group, an optionally substituted benzyl group;
• R3 is a linear or branched C1-10 alkyl group, an acetyl group, an optionally substituted benzyl group, a SO2R6 group;
• R4 and R5 taken together form a double bond or a three member ring;
• R6 is a linear or branched C1-10 alkyl group, or an optionally substituted aryl group;
• comprising:
• a) reacting an adamantane derivative of formula (VII)
• with a compound of formula (VIII)
• wherein R, R4 and R5 have the above reported meanings;
• in the presence of a condensing agent and optionally in the presence of a base, in an aprotic solvent to give compounds of formula (VI) wherein X represents an oxygen atom;
• and optionally
• b) reacting the compound formula (VI) obtained in step a) with NH2R1, in the presence of a base or an acid, in a polar solvent to give compounds of formula (VI) wherein X represents a N—R1 group, wherein R1 has the above reported meanings.

A process for the preparation of compounds of formula (VI),

• wherein
• X is an oxygen atom or a NR1 group;
• R is a CONH2 group, a COOR2 group or a CN group;
• R1 is a hydrogen atom, a hydroxy group, an OR3 group, or an optionally substituted benzyl group;
• R2 is a linear or branched C1-10 alkyl group, an optionally substituted benzyl group;
• R3 is a linear or branched C1-10 alkyl group, an acetyl group, an optionally substituted benzyl group, a SO2R6 group;
• R4 and R5 taken together form a double bond or a three member ring;
• R6 is a linear or branched C1-10 alkyl group, or an optionally substituted aryl group;
• comprising:
• a1) reacting an adamantane intermediate of formula (VII)
• with NH2R1 wherein R1 has the above reported meanings, in the presence of a base or an acid, in a polar solvent to give compounds of formula (IX)
• wherein R1 has the above reported meanings;
• and
• b1) reacting the compound of formula (IX) obtained in step a1) and a compound of formula (VIII)
• wherein R, R4 and R5 have the above reported meanings;
• in the presence of a condensing agent and a base, in a polar aprotic solvent to give compounds of formula (VI) wherein X and R1 have the above reported meanings.

A process for the preparation of compounds of formula (X)

• wherein R7 is a CONH2 group or a CN group,
• comprising reacting a compound of formula (VI-1)
• wherein
• R7 has the above reported meanings;
• R1 is a hydrogen atom, a hydroxy group, an OR3 group, or an optionally substituted benzyl group;
• R3 is a linear or branched C1-10 alkyl group, an acetyl group, a optionally substituted benzyl group, a SO2R6 group;
• R6 is a linear or branched C1-10 alkyl group, or an optionally substituted aryl group;
• with hydrogen, or hydrogen donor compounds, or hydrides, optionally in the presence of a suitable catalyst;
• or with reducing metals in the presence of a polar protic solvent.