Pyrrolo[2,3-D]pyrimidine derivatives; their intermediates and synthesis

摘要

A method of making a pyrrolo [2,3-d] pyrimidine compound of the Formula Iva comprising coupling an activated pyrrolopyrimidine compound of the Formula (lIa) wherein L1 is a leaving group and X1 is an activating group; with an amine of the Formula (lIla), or a salt thereof; wherein R1 is (C1 -C5)alkyl; a is an integer from 0 to 4; R2 is hydrogen or (C1 - C5) alkyl and P is a nitrogen protecting group; in the presence of a base to afford a coupled product of the Formula (IVa). Specifically novel synthetic methods and intermediates for the synthesis of 3- {(3R, 4R)-4-methyl-(7H-pyrrolo[2,3-d] pyrimidin-4-yl)-amino}-piperidin-l-yl)-3-oxo-propionitrile and its corresponding citrate salt are disclosed.