WO2010026122 Heterocyclic PIM-kinase inhibitors
| Steps | Conditions | Reactions |
| a | EtOH | Tertiary amine synthesis (Aromatic substitution) |
| b | H2 / Pd-C / EtOH | Primary amine synthesis (Nitro reduction) |
| Steps | Conditions | Reactions |
| a | N-(benzyloxycarbonyloxy)succinimide / DIEA / DCM | Cbz protection |
| b | DPPA / t-BuOH / DIEA | Curtius rearrangement |
| Steps | Conditions | Reactions |
| a | DAST / DCM | Fluorination |
| Steps | Conditions | Reactions |
| a | MsCl / Et3N / DCM | Mesyl synthesis |
| b | Pyridine | Cyclisation |
| c |
Boc2O / Et3N / DMAP / DCM |
Boc protection |
| Steps | Conditions | Reactions |
| a |
1. NH4OH / EtOH 2. Boc2O / Et3N / DCM |
Epoxide opening |
| Steps | Conditions | Reactions |
| a | NaHMDS / Boc2O / THF | Boc protection |
| b | H2 / Rh-C / PtO2 / AcOH | Piperidine synthesis (Pyridine reduction) |
| Steps | Conditions | Reactions |
| a | MeOH / EDCI / DMAP / DCM | Ester synthesis (Esterification) |
| b | NaBH4 / LiCl / THF | Hydroxyl synthesis (Ester reduction) |
| c |
Perfluorobutanesulfonylfluoride / triethylamine.3HF / Et3N / THF |
Fluorination |
| Steps | Conditions | Reactions |
| a | Imidazole / DMAP / TBDMSCl / DCM | TBDMS protection |
| b | H2 / Pd-C / EtOH:EtOAc 1:1 | CBz deprotection |
| Steps | Conditions | Reactions |
| a | Pd(dppf)Cl2-DCM / THF | Negishi coupling |
| Steps | Conditions | Reactions |
| a | Pd(dppf)Cl2-DCM / DIPEA / Toluene:EtOH (1:1) | Suzuki reaction |
| b | BBr3 / DCM | Methoxy deprotection |
| c |
1,1,1-trifluoro-N-Phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide / DIPEA / DCM |
Triflyl synthesis |
| Steps | Conditions | Reactions |
| a | Pd(OAc)2 / BINAP / Cs2CO3 / dioxane | Buchwald-hartwig amination |