WO 2010038165 Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
Scaffold: 1,5-naphthyridine
Biological target:
Phosphoinositide 3-kinase alpha: PI3-Kα
Mammalian target of rapamycin protein kinase: mTOR
Activity:
Dual inhibitors
| Steps | Conditions | Reactions |
| a | EtOH | Secondary amine synthesis (Nucleophilic substitution) |
| b | Ph2O | Cyclisation |
| c | POCl3 | Chlorination |
| Steps | Conditions | Reactions |
| a | Pd(PPH3)4 / K2CO3 / toluene | Suzuki reaction |
| b | K2CO3 / DMA | Secondary amine synthesis (Aromatic substitution) |
| c | LIOH / MeOH / THF | Carboxylic acid synthesis (Ester hydrolysis) |
| d | DPPA / Et3N / DMF | Curtius rearrangement / Cyclisation |
| e | MeI / NaH / DMF | N-Methylation |
| f | TMSI / CHCl3 | CBz deprotection |
| Steps | Conditions | Reactions |
| a |
HCHO / HCOOH
|
N-Methylation |
| b |
CH3COCl / Et3N /DMSO
|
Acetylation |
| Steps | Conditions | Reactions |
| a |
|
Amide synthesis (HATU coupling) |
| b |
2-chloroacetamide / Et3N /DMSO
|
Tertiary amine synthesis (Nucleophilic substitution) |
| c |
Methyl isocyanate / Et3N / THF
|
Urea synthesis |
| Steps | Conditions | Reactions |
| a |
Et3N / DCM
|
Carbamate synthesis |
| b | NH3 / DMSO |
Urea synthesis |
| Steps | Conditions | Reactions |
| a |
Et3N / DCM
|
Amide synthesis |
| b | NH3 / DMSO |
Hydroxyl synthesis (Ester hydrolysis) |