Pyridine → Doxorubicin

HRID 1168106Notes

Reaction equation

HRID 1168106 reaction equation
N1C=CC=CC=1.[CH3:7][C@@H:8]1[O:13][C@@H:12]([O:14][C@@H:15]2[C:20]3=[C:21]([OH:38])[C:22]4[C:34](=[O:35])[C:33]5[C:28](=[CH:29][CH:30]=[CH:31][C:32]=5[O:36][CH3:37])[C:26](=[O:27])[C:23]=4[C:24]([OH:25])=[C:19]3[CH2:18][C@@:17]([OH:43])([C:39]([CH2:41][OH:42])=[O:40])[CH2:16]2)[CH2:11][C@H:10]([NH2:44])[C@@H:9]1[OH:45].Cl.C(N(CC)CC)C>C(Cl)Cl>[CH3:7][C@@H:8]1[O:13][C@@H:12]([O:14][C@@H:15]2[C:20]3=[C:21]([OH:38])[C:22]4[C:34](=[O:35])[C:33]5[C:28](=[CH:29][CH:30]=[CH:31][C:32]=5[O:36][CH3:37])[C:26](=[O:27])[C:23]=4[C:24]([OH:25])=[C:19]3[CH2:18][C@@:17]([OH:43])([C:39]([CH2:41][OH:42])=[O:40])[CH2:16]2)[CH2:11][C@H:10]([NH2:44])[C@@H:9]1[OH:45]

Participants

5

Reactant 3

HCID 1049PyridineHCID 8471TriethylamineHCID 443939Doxorubicin Hydrochloride

Product 1

HCID 31703Doxorubicin

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3 g of mPEG-PLGA obtained above and 80 mg of p-nitrofluoroformate, a linker compound, were dissolved in 30 ml of methylene chloride. Then, 63 mg of pyridine was added to the solution, and reacted for 3 hours under a stream of nitrogen gas. And then, reaction product was precipitated by adding cold diethylether, filtered on a filter paper and dried under a reduced pressure. After dissolving 0.25 g of dried reaction product in 7.5 ml of dimethylformamide, 10 mg of doxorubicin-HCl(Sigma Chem. Co., U.S.A.) and 6.75 mg of triethylamine were added and reacted at room temperature for 24 hours under a nitrogen gas to obtain doxorubicin-conjugated micelle monomer(see: FIG. 2). The said micelle monomers were dispersed in 300 ml of triple distilled water to form doxorubicin-conjugated sustained release micelles, and free doxorubicin was removed by dialyzing the mixture 5 times against 3 L of triple distilled water each time. Doxorubicin-conjugated sustained release micelles were pelletized by ultracentrifugation, and freeze-dried after removing supernatant, and then, stored in the form of doxorubicin-conjugated micelle monomer.

Workup

  1. customreacted for 3 hours under a stream of nitrogen gas
  2. customAnd then, reaction product
  3. customwas precipitated
  4. additionby adding cold diethylether
  5. filtrationfiltered on a filter paper
  6. customdried under a reduced pressure
  7. dissolutionAfter dissolving
  8. custom0.25 g of dried reaction product in 7.5 ml of dimethylformamide
  9. customreacted at room temperature for 24 hours under a nitrogen gas

Sources & evidence

ORD record
ord-b0fc7084691d42c0aa052f0f232efca3
Source dataset
uspto-grants-2003_09
Patent number
US06623729B2

Reaction notes

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