Trisodium Phosphate → Linifanib

HRID 409947Notes

Reaction equation

HRID 409947 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([NH:8][C:9]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:19]=[CH:20][CH:21]=[C:22]4[NH:26][N:25]=[C:24]([NH2:27])[C:23]=34)=[CH:16][CH:17]=2)=[O:10])[CH:7]=1.Cl.P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+]>C(OCC)(=O)C.C(O)C>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([NH:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[CH:20][CH:21]=[C:22]4[NH:26][N:25]=[C:24]([NH2:27])[C:23]=34)=[CH:14][CH:13]=2)=[O:10])[CH:7]=1

Participants

5

Reactant 2

HCID 24243Trisodium PhosphateHCID 86762482HCID 86762482, compound2×

Product 1

HCID 11485656LinifanibYield 92%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of ABT-869 hydrochloride in ethyl acetate and ethanol, in which the ABT-869 hydrochloride was completely soluble, was mixed with dibasic sodium phosphate. The organic layer was separated, treated with decolorizing carbon, and filtered. A small quantity of L-ascorbic acid was added, and the solution was concentrated. The ethyl acetate was removed by azeotropic distillation with ethanol. Additional ethanol may be added and the solution heated to dissolve any solid that forms. The solution was cooled to 25° C. and diluted with water, causing ABT-869•¼Ethanolate Crystalline Form 1 to crystallize. The product was isolated, washed with water, and dried under reduced pressure, while monitoring residual ethyl acetate and ethanol (by gas chromatography (GC)) and water (by Karl Fischer (KF)). A yield of 92% is typical.

Workup

  1. customThe organic layer was separated
  2. additiontreated with decolorizing carbon
  3. filtrationfiltered
  4. additionA small quantity of L-ascorbic acid was added
  5. concentrationthe solution was concentrated
  6. customThe ethyl acetate was removed by azeotropic distillation with ethanol
  7. additionAdditional ethanol may be added
  8. temperaturethe solution heated
  9. dissolutionto dissolve any solid that forms
  10. additiondiluted with water
  11. customto crystallize
  12. customThe product was isolated
  13. washwashed with water
  14. customdried under reduced pressure

Sources & evidence

ORD record
ord-ff5f5bc2074e4f99ac8924c15fd3527b
Source dataset
uspto-grants-2014_06
Patent number
US08759538B1

Reaction notes

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