Trials of N-alkylation of 7 and 2a.
| Entry | Base (equiv.) | Solvent | T (°C) | 7 (equiv.) | Yieldb |
|---|---|---|---|---|---|
| 1 | TEA (2.2) | DMF | 60 | 1.5 | N. R.c |
| 2 | DIPEA (2.2) | DMF | 60 | 1.5 | N. R. |
| 3 | NaHCO3 (2.2) | DMF | 60 | 1.5 | Trace |
| 4 | DBU (2.2) | DMF | 60 | 1.5 | Trace |
| 5 | CH3ONa (1.1) | DMF | 60 | 1.5 | <10% |
| 6 | t-BuOK (1.1) | DMF | 60 | 1.5 | <10% |
| 7 | NaOH (1.1) | H2O | 60 | 1.5 | Trace |
| 8 | K2CO3 (2.2) | DMF | 60 | 1.5 | 25% |
| 9 | K2CO3 (2.2) | ACN | 60 | 1.5 | <15% |
| 10 | K2CO3 (2.2) | DMF | −20 | 1.5 | Trace |
| 11 | K2CO3 (2.2) | DMF | 0 | 1.5 | Trace |
| 12 | K2CO3 (2.2) | DMF | R. T. | 1.5 | 40%d |
| 13 | K2CO3 (2.2) | DMF | 40 | 1.5 | 51%d |
| 14 | K2CO3 (2.2) | DMF | 40 | 2.0 | 60%d |
a
The reaction was performed according to the conditions unless otherwise mentioned. A mixture of triazone 2 (100 mg) and base was added into 2 mL of solvent. After 30–60 min, de-methyl triazole 7 was added into the mixture and stirred for 5 h with hourly monitoring by TLC. If necessary, the crude product was obtained by common workup and purified by column purification.
b
TLC was used to monitor the reaction unless otherwise mentioned.
c
Not reacted.
d
Isolated yield.