1,2,3,4-Tetrahydroisoquinoline → HCID 67903286, compound

Participants

Reaction Steps

To a stirred solution of 1-[(3-fluoro-4-pyridinyl)propylamino]-3-methyl-1H-indol-5-ol (2.51 g) in anhydrous tetrahydrofuran (56 ml) was added 1,1'-carbonyl diimidazole (2.72 g) at room temperature under nitrogen. After 24 hours the reaction appeared complete by TLC (silica gel, 60% EtOAc/hexane) and acetic acid (1.60 ml) was added to the reaction mixture followed by the dropwise addition of a solution of 1,2,3,4-tetrahydroisoquinoline (1.58 ml) in tetrahydrofuran (5.0 ml) and acetic acid (0.75 ml). After 72 hours, the reaction was not complete by TLC (60% EtOAc/dichloromethane) and an additional equivalent of 1,2,3,4-tetrahydroisoquinoline (1.05 ml) was added as a tetrahydrofuran (5.0 ml) and acetic acid (0.51 ml) solution. After 1.5 hours the reaction appeared complete and the mixture was poured into NaHCO3 (aq) and ether. The layers were separated and the aqueous phase was extracted with ether (3x). The combined organic layers were washed successively with NaHCO3 (aq) and brine, and dried (Na2SO4). The organic phase was filtered and concentrated to give a crude product. Purification via flash column chromatography (silica gel., 30% EtOAc/dichloromethane) afforded 2.70 g of the desired product as an oil which solidified on standing. Recrystallization from ether (2x) gave a solid which was filtered and washed with ether, m.p. 157°-160° C.

Provenance & Evidence