Table 1. Optimization of Ugi-4CR Conditions.
| entrya | amine component | solvent | T (°C) | yieldb |
|---|---|---|---|---|
| 1 | NH4Cl (9a) | MeOH/H2O = 3:1 | r.t. | 33% |
| 2 | NH4Cl | MeOH | r.t. | 41% |
| 3 | NH4Cl | MeOH/H2O = 3:1 | 55 °C | 33% |
| 4 | ammonia in water (9b) | TFE | r.t. | trace |
| 5 | ammonia in MeOH (9c) | TFE | 55 °C | 62% |
| 6 | ammonia in MeOH | TFE | r.t. | 75% |
| 7 | ammonia in MeOH | MeOH | r.t. | 60% |
| 8c | 2,4-dimethoxybenzylamine (9d) | TFE | r.t. | 59% |
a
Reaction conditions: 6a (1 mmol), 7a (1 mmol), 8a (1 mmol), 9 (1 mmol), solvent (1 mL).
b
Isolated yields.
c
Followed by HCl-catalyzed cleavage.