Dichloromethane → Tivantinib

Participants

Reaction Steps

A feed solution for multicolumn chromatography (MCC) is prepared by dissolving Compound 8 DCM in methanol. The resulting DCM/methanol co-solvent is distilled until the residual level of DCM in the feed solution reaches a level acceptable for contact with the Chiral Stationary Phase (CSP), i.e., <0.1% by weight. The batch is diluted in a mixture of methanol/Acetonitrile (9:1) to a concentration of 50 mg/mL and introduced to the chromatographic system. Chiralpak AZ (CSP) can be utilized. The raffinate is monitored by chiral HPLC analysis and chromatographic parameters are tuned to obtain >99% chiral purity of (−)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione (Compound 10 in Scheme I). Raffinate is pooled and concentrated batchwise as the separation proceeds. The collected raffinate is taken to a larger reactor and the volume is reduced. Compound 10 is then isolated by crystallization.

Provenance & Evidence