Diisopropylethylamine → Doxorubicin

HRID 968449Notes

Reaction equation

HRID 968449 reaction equation
[CH3:1][C@@H:2]1[O:7][C@@H:6]([O:8][C@@H:9]2[C:14]3=[C:15]([OH:32])[C:16]4[C:28](=[O:29])[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][C:26]=5[O:30][CH3:31])[C:20](=[O:21])[C:17]=4[C:18]([OH:19])=[C:13]3[CH2:12][C@@:11]([OH:37])([C:33]([CH2:35][OH:36])=[O:34])[CH2:10]2)[CH2:5][C@H:4]([NH2:38])[C@@H:3]1[OH:39].Cl.C(N(C(C)C)CC)(C)C.CO.C(Cl)Cl>CN(C=O)C>[CH3:1][C@@H:2]1[O:7][C@@H:6]([O:8][C@@H:9]2[C:14]3=[C:15]([OH:32])[C:16]4[C:28](=[O:29])[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][C:26]=5[O:30][CH3:31])[C:20](=[O:21])[C:17]=4[C:18]([OH:19])=[C:13]3[CH2:12][C@@:11]([OH:37])([C:33]([CH2:35][OH:36])=[O:34])[CH2:10]2)[CH2:5][C@H:4]([NH2:38])[C@@H:3]1[OH:39]

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 443939Doxorubicin HydrochlorideHCID 21226129Dichloromethane methanol

Product 1

HCID 31703Doxorubicin

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of doxorubicin hydrochloride (58.5 mg, 0.10 mmol), phosphorylating agent (26.7 mg, 0.12 mmol) and diisopropylethylamine (45.5 μL, 0.26 mmol) in 3.0 mL of DMF was stirred for 19 h at room temperature. Treated with additional diisopropylethylamine (60 μL, 0.34 mmol) and phosphorylating agent (31.8 mg, 0.14 mmol) and stirred for an additional 31 h. The solvent was removed under reduced pressure and the residue was chromatographed on a short silica column eluting with 5% methanol in dichloromethane. The product obtained was treated with CH3OH/CH2Cl2 and precipitated with ether. The red solid was filtered, rinsed with ether and dried under vacuum at room temperature.

Workup

  1. stirringstirred for an additional 31 h
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was chromatographed on a short silica column
  4. washeluting with 5% methanol in dichloromethane
  5. customThe product obtained
  6. customprecipitated with ether
  7. filtrationThe red solid was filtered
  8. washrinsed with ether
  9. customdried under vacuum at room temperature

Sources & evidence

ORD record
ord-1df7a875897645eca9f8ceb64e7186e6
Source dataset
uspto-grants-2007_12
Patent number
US07303739B2

Reaction notes

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