Scheme 4. Synthetic Route for 29-31.
Reagents and conditions: a) (R)-piperidine-3-carboxylic acid, Na2CO3, THF, H2O, rt, 98%; b) 4,4-difluoropiperidine, HATU, DIEA, DMF, rt, 32%; c) dimethylphosphine oxide or diethylphosphine oxide, Pd(OAc)2, XantPhos, K3PO4, DMF, 120 °C, 88-95%; d) i. LiOH, THF, H2O, rt; ii. 4,4-difluoropiperidine, HATU, DIEA, DMF, rt, 83-95%.