Process for preparing enantiomerically enriched substituted pyrrolo[2,3-d]pyrimidines

A process for preparing a compound of Formula I:

• wherein:
• Y1 is H or D;
• each Y2 is H or D, wherein each Y2 is identical;
• each Y3 is H or D, wherein each Y2 is identical;
• and
• (i) PG is H;
• or
• (ii) PG is a protecting group selected from:
• wherein the process comprises:
• (a) reacting a compound of Formula II:
• wherein each of Y1, Y2, Y3, and PG in Formula II is defined as in Formula I;
• with hydrogen gas in the presence of a hydrogenation catalyst comprising rhodium and a chiral phosphine ligand, (L), according to Formula III:
• wherein:
• R2a is independently H, CH3, CF3, or OCH3;
• R2b is independently H, CH3, CF3, or OCH3;
• R3a is independently H, CH3, CF3, or OCH3;
• R3b is independently H, CH3, CF3, or OCH3;
• R4 is independently H, CH3, CF3, or OCH3;
• and
• R5 is independently alkyl or cycloalkyl, wherein alkyl is independently secondary or tertiary;
• to provide the compound of Formula I above;
• or
• (b) reacting a compound of Formula VII:
• wherein each of Y2, Y3, and PG in Formula VII is defined as in Formula I;
• with hydrogen gas in the presence of a hydrogenation catalyst comprising rhodium and a chiral phosphine ligand according to Formula VI:
• wherein:
• each of R2a, R2b, R3a, R3b, and R4 in Formula VI is defined as in Formula III;
• and
• each R5a is phenyl;
• to provide the compound of Formula I above;
• or
• (c) reacting a compound of Formula VII:
• wherein each of Y2, Y3, and PG in Formula VII is defined as in Formula I;
• with hydrogen gas in the presence of a hydrogenation catalyst comprising rhodium and a chiral phosphine ligand according to Formula VIII:
• wherein:
• each of R2a, R2b, R3a, R3b, and R4 in Formula VIII is defined as in Formula III;
• and
• each R5a is C(CH3)3;
• to provide the compound of Formula I above.