Indole-3-acetamide → 3-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione

Participants

Reaction Steps

In step 1 of scheme I, lilolidine (Compound 4), was treated with oxalylchloride to give the acyl chloride in methyl tert-butyl ether (MTBE) reaction solvent. The addition of methanol was sufficient to afford the intermediate ketoester, 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)oxoacetic acid methyl ester (Compound 5). In Step 2 of the reaction, Compound 5 and indole-3-acetamide (Compound 5a) were combined to produce 3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrole-2,5-dione (Compound 6). As described in detail in the following examples, it is not necessary to isolate intermediate Compound 5 to produce Compound 6. A solvent swap from MTBE into tetrahydrofuran (THF) was necessary prior to conducting Step 2, since both 5 and 5a have very poor solubility in MTBE. Following the addition of Compound 5a to consume Compound 5 in THF in the presence of base, HCl was added to complete the reaction to afford crude Compound 6. Crude Compound 6 was then purified from DCM and heptane to afford Compound 6 of sufficient purity to proceed to the next step. A detailed description of this process is shown in Example 1.

Provenance & Evidence