2,2-Dimethylsuccinic anhydride → 4-{4-[5-(4-Iodo-3-methyl-phenylcarbamoyl)-pyridin-2-yl]-piperazin-1-yl}-dimethyl-4-oxo-butyric acid

HRID 2190647Notes

Reaction equation

HRID 2190647 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20](=[O:30])[NH:21][C:22]3[CH:27]=[CH:26][C:25]([I:28])=[C:24]([CH3:29])[CH:23]=3)=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.[CH3:31][C:32]1([CH3:39])[CH2:37]C(=O)[O:35][C:33]1=[O:34]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[I:28][C:25]1[CH:26]=[CH:27][C:22]([NH:21][C:20]([C:17]2[CH:18]=[CH:19][C:14]([N:11]3[CH2:10][CH2:9][N:8]([C:6](=[O:7])[CH2:31][C:32]([CH3:39])([CH3:37])[C:33]([OH:35])=[O:34])[CH2:13][CH2:12]3)=[N:15][CH:16]=2)=[O:30])=[CH:23][C:24]=1[CH3:29]

Participants

5

Reactant 2

HCID 870672,2-Dimethylsuccinic anhydrideHCID 593181204-[5-(4-Iodo-3-methyl-phenylcarbamoyl)-pyridin-2-yl]-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 593180564-{4-[5-(4-Iodo-3-methyl-phenylcarbamoyl)-pyridin-2-yl]-piperazin-1-yl}-dimethyl-4-oxo-butyric acid

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

4-[5-(4-Iodo-3-methyl-phenylcarbamoyl)-pyridin-2-yl]-piperazine-1-carboxylic acid tert-butyl ester (35 mg, 0.07 mmol) was dissolved in 30% TFA in CH2Cl2 solution at room temperature. The mixture was stirred for 30 min and then partitioned between EtOAc and H2O. The water layer was made basic by the addition of Na2CO3. The organic layer was then collected washed with water dried over Na2SO4, filtered and evaporated. The residue was dissolved in CH2Cl2 and treated with 2,2-dimethysuccinic anhydride (13 mg, 0.10 mmol). After stirring at room temperature for 4 h the mixture was concentrated to a residue and washed with excess of hexanes to afford the product. HRMS m/z calcd for C23H27N4O4I [M+H]+: 551.1150. Found: 551.1152.

Workup

  1. custompartitioned between EtOAc and H2O
  2. additionThe water layer was made basic by the addition of Na2CO3
  3. customThe organic layer was then collected
  4. washwashed with water
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe residue was dissolved in CH2Cl2
  9. stirringAfter stirring at room temperature for 4 h the mixture
  10. concentrationwas concentrated to a residue
  11. washwashed with excess of hexanes
  12. customto afford the product

Sources & evidence

ORD record
ord-fdf55c4b659b4186b67630dacaf57bb4
Source dataset
uspto-grants-2012_12
Patent number
US08324385B2

Reaction notes

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