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

HRID 2180911Notes

Reaction equation

HRID 2180911 reaction equation
[CH3:1][C@@H:2]1[CH2:24][C:23]2[C:25](=[O:26])[C:18](=[CH:19][C:20]([C:22]=2OC)=[O:21])[NH:17][C:15](=[O:16])[C:14]([CH3:29])=[CH:13][CH:12]=[CH:11][C@H:10]([O:30][CH3:31])[C@@H:9]([O:32][C:33]([NH2:35])=[O:34])[C:8]([CH3:36])=[CH:7][C@H:6]([CH3:37])[C@@H:5]([OH:38])[C@@H:4]([O:39][CH3:40])[CH2:3]1.[CH3:41][N:42]([CH3:46])[CH2:43][CH2:44][NH2:45]>C(Cl)Cl>[CH3:1][C@@H:2]1[CH2:24][C:23]2[C:25](=[O:26])[C:18](=[CH:19][C:20]([C:22]=2[NH:45][CH2:44][CH2:43][N:42]([CH3:46])[CH3:41])=[O:21])[NH:17][C:15](=[O:16])[C:14]([CH3:29])=[CH:13][CH:12]=[CH:11][C@H:10]([O:30][CH3:31])[C@@H:9]([O:32][C:33]([NH2:35])=[O:34])[C:8]([CH3:36])=[CH:7][C@H:6]([CH3:37])[C@@H:5]([OH:38])[C@@H:4]([O:39][CH3:40])[CH2:3]1

Participants

4

Reactant 2

HCID 66053N,N-DimethylethylenediamineHCID 5288382Geldanamycin

Product 1

HCID 528867417-Demethoxy-17-[[2-(dimethylamino)ethyl]amino]geldanamycinYield 96.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  1. customAfter the organic layer and the aqueous layer became visually separated
  2. extractionthe aqueous layer was extracted with methylene chloride (2×10 mL)
  3. washThe combined methylene chloride solution was washed with water (2×10 mL)
  4. dry with materialdried with MgSO4 (J.T. Baker, Lot No. E01098)
  5. customevaporated in an aspirator
  6. customThe remaining residue was purified by silica gel chromatography (30 g) (EM Science, Lot No. 325TA509634)
  7. washeluting with 10% methanol (Chempure, Lot No. M178KMDH) in methylene chloride
  8. additionThe fractions containing product
  9. concentrationconcentrated in an aspirator
  10. dissolutionThe residue was then dissolved in hot methylene chloride (3 mL)
  11. temperaturecooled to room temperature
  12. additiondiluted with hexane (60 mL) (Chempure, Lot No. M148KMRC)
  13. stirringThis mixture was then stirred at room temperature for 30 minutes
  14. customA purple powder formed
  15. filtrationwas collected by filtration
  16. washwashed with hexane (2×10 mL)
  17. customdried at 55° C./0.1 mmHg for 6 hours
  18. customto give pure target compound

Sources & evidence

ORD record
ord-5b723eab1cab4474ad7cf0ac03a50f58
Source dataset
uspto-grants-2005_05
Patent number
US06890917B2

Reaction notes

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