Process for the preparation of purine derivatives exhibiting cdk inhibitory activity

A process according to any preceding claim for preparing a compound of formula [1], or a pharmaceutically acceptable salt thereof:

• said process comprising the steps of:
• (i) forming a reaction mixture comprising a compound of formula [2], and a compound of formula [3];
• (ii) heating said reaction mixture to a temperature of at least about 130° C. to form a compound of formula [1];
• (iii) isolating said compound of formula [1] from the mixture and optionally recovering unreacted compound of formula [3];
• and
• (iv) optionally converting said compound of formula [1] into salt form.

A process for preparing a compound of formula [I], or a pharmaceutically acceptable salt thereof,

• wherein R1 and R2 are each independently H, alkyl or haloalkyl;
• R3 and R4 are each independently H, alkyl, haloalkyl or aryl;
• R5 is alkyl, alkenyl, cycloalkyl or cycloalkyl-alkyl, each of which may be optionally substituted with one or more OH groups;
• R6 is selected from cyclopropylamino, cyclopropylmethylamino, cyclobutylamino, cyclobutylmethylamino and
• where one of X, Y and Z is N and the remainder are CR9;
• R7, R8 and each R9 are independently H, alkyl or haloalkyl, wherein at least one of R7, R8 and R9 is other than H;
• said process comprising the steps of:
• (a) treating a compound of formula [VI] with R6—NH2 or a salt thereof to form a compound of formula [VII];
• (b) treating said compound of formula [VII] with R5Br to form a compound of formula [II];
• (c) forming a reaction mixture comprising a compound of formula [II], and a compound of formula [III] and heating said reaction mixture to a temperature of at least about 130° C. to form a compound of formula [I];
• (d) isolating said compound of formula [I] from the mixture and optionally recovering unreacted compound of formula [III];
• and
• (e) optionally converting said compound of formula [I] into salt form.

A process of preparing a compound of formula [1], or a pharmaceutically acceptable salt thereof, said process comprising the steps of:

• (a) treating a compound of formula [6] with a compound of formula [9], or a salt thereof, to form a compound of formula [7];
• (b) treating said compound of formula [7] with isopropyl bromide to form a compound of formula [2];
• (c) forming a reaction mixture comprising a compound of formula [2], and compound of formula [3] and heating said reaction mixture to a temperature of at least about 130° C. to form a compound of formula [1];
• (d) isolating said compound of formula [1] from the mixture and optionally recovering unreacted compound of formula [3];
• and
• (e) optionally converting said compound of formula [1] into salt form.

A process for preparing a compound of formula [I], or a pharmaceutically acceptable salt thereof,

• wherein:
• R1 and R2 are each independently H, alkyl or haloalkyl;
• R3 and R4 are each independently H, alkyl, haloalkyl or aryl;
• R5 is alkyl, alkenyl, cycloalkyl or cycloalkyl-alkyl, each of which may be optionally substituted with one or more OH groups;
• R6 is selected from cyclopropylamino, cyclopropylmethylamino, cyclobutylamino, cyclobutylmethylamino and
• where one of X, Y and Z is N and the remainder are CR9;
• R7, R8 and each R9 are independently H, alkyl or haloalkyl, wherein at least one of R7, R8 and R9 is other than H;
• said process comprising the steps of:
• (i) forming a reaction mixture comprising a compound of formula [II], and a compound of formula [III];
• (ii) heating said reaction mixture to a temperature of at least about 130° C. to form a compound of formula [I];
• (iii) optionally isolating said compound of formula [I] from the mixture and optionally recovering unreacted compound of formula [III];
• and
• (iv) optionally converting said compound of formula [I] into salt form.