N,N-Dimethylethylenediamine → 17-Demethoxy-17-[[2-(dimethylamino)ethyl]amino]geldanamycin

Participants

Reaction Steps

A mixture of geldanamycin (1.5 g, 2.68 mmol) (NCI, Lot No. 3059-25-1) and N,N-dimethylethylenediamine (1.5 mL, 13.7 mmol) (Aldrich, Lot No. 04216AL) in dry methylene chloride (30 mL) (Burdick & Jackson, Lot No. BH516) was stirred at room temperature for 1 hour and subsequently poured into ice water (50 mL). After the organic layer and the aqueous layer became visually separated, the aqueous layer was extracted with methylene chloride (2×10 mL). The combined methylene chloride solution was washed with water (2×10 mL), dried with MgSO4 (J.T. Baker, Lot No. E01098) and evaporated in an aspirator. The remaining residue was purified by silica gel chromatography (30 g) (EM Science, Lot No. 325TA509634) eluting with 10% methanol (Chempure, Lot No. M178KMDH) in methylene chloride. The fractions containing product were combined and concentrated in an aspirator. The residue was then dissolved in hot methylene chloride (3 mL), cooled to room temperature and diluted with hexane (60 mL) (Chempure, Lot No. M148KMRC). This mixture was then stirred at room temperature for 30 minutes. A purple powder formed and was collected by filtration, washed with hexane (2×10 mL) and dried at 55° C./0.1 mmHg for 6 hours to give pure target compound. Approximately 1.59 g of 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (96%) was isolated and used in Example 1.

Provenance & Evidence