Table 1.

Optimization of the Pictet–Spengler cyclization step^a

Entrya	Acid	Solvent	Tempb (°C)	Time (h)	Convc (%)
1	HCOOH	MeOH	rt	18	—
2	HCOOH	MeOH	80 °C	18	—
3	HCOOH	—	rt	18	—
4	HCOOH	—	80 °C	18	—
5	CF3COOH	MeOH	80 °C	18	Traces
6	CF3COOH	CH2Cl2	rt	18	Traces
7	CF3COOH	CH3CN	60 °C	18	Traces
8	CF3COOH	Toluene	80 °C	18	Traces
9	CF3COOH	—	50 °C	18	Traces
10	CH3SO3H	Toluene	80 °C	18	Traces
11	CH3SO3H	MeOH	80 °C	18	Traces
12	CH3SO3H	—	80 °C	18	Traces
13	CH3SO3H	—	rt	18	67d

^aReaction conditions: 1a (0.3 mmol), acid (30.0 mmol), solvent (3.0 mL).

^bThe reaction was performed under classical heating conditions.

^cDetermined by SFC–MS analysis of crude reaction mixture.

^dIsolated product.