Propylphosphonic anhydride → Camptothecin

HRID 1068537

Reaction equation

HRID 1068537 reaction equation
[CH3:1][CH2:2][C@@:3]1([OH:26])[C:8](=[O:9])[O:7][CH2:6][C:5]2[C:10]([N:12]3[C:24](=[CH:25][C:4]1=2)[C:23]1[N:22]=[C:21]2[C:16]([CH:17]=[CH:18][CH:19]=[CH:20]2)=[CH:15][C:14]=1[CH2:13]3)=[O:11].C(O)(C(F)(F)F)=O.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.CN(C)N1C=CC=CC1>C(OCC)(=O)C.ClCCl>[CH3:1][CH2:2][C@@:3]1([OH:26])[C:8](=[O:9])[O:7][CH2:6][C:5]2[C:10]([N:12]3[C:24](=[CH:25][C:4]1=2)[C:23]1[N:22]=[C:21]2[C:16]([CH:17]=[CH:18][CH:19]=[CH:20]2)=[CH:15][C:14]=1[CH2:13]3)=[O:11]

Participants

6

Reactant 3

HCID 111923Propylphosphonic anhydrideHCID 6453552N,N-dimethylpyridin-1-amineHCID 86584209HCID 86584209, compound

Product 1

HCID 24360CamptothecinYield 8,851.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2.0 g (0.10 mmoles) of m-PEG20k acid, 60 mg (0.06 mmoles) of diaminopimelic camptothecin TFA salt, 0.064 mo (0.10 mmoles) of a 50% solution of 1-propanephosphonic acid cyclic anhydride in ethyl acetate and 25 mg (0.20 mmoles) of N-dimethylamino pyridine in 20 ml of dry dichloromethane was stirred at room temperature overnight followed by washing with 1% aqueous sodium bicarbonate and 0.1N HCl solution. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation in vacuo. The residue was crystallized from 2-propanol to yield 1.85 g (93% yield)of product.

Workup

  1. washby washing with 1% aqueous sodium bicarbonate and 0.1N HCl solution
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. customthe solvent was removed by distillation in vacuo
  4. customThe residue was crystallized from 2-propanol

Sources & evidence

ORD record
ord-e17ba7ea6d124281af76da0b7571ec03
Source dataset
uspto-grants-2001_06
Patent number
US06251382B1

Linked notes

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