Acetic Anhydride → HCID 68089211, compound

HRID 449164Notes

Reaction equation

HRID 449164 reaction equation
C([O:4][C:5](=[O:7])[CH3:6])(=O)C.C([O-])=O.[Na+].I[C:13]1C=[CH:17][N:16]=[C:15]([C:19]2([NH:22][C:23]([C:25]3([NH:28][C:29]([C:31]4[N:35]5[C@@:36]([CH2:49][C:50]6[CH:55]=[CH:54][C:53]([C:56]#[N:57])=[CH:52][CH:51]=6)([CH3:48])[C:37](=[O:47])[N:38]([C:39]6[CH:44]=[C:43]([Cl:45])[CH:42]=[C:41]([Cl:46])[CH:40]=6)[C:34]5=[N:33][CH:32]=4)=[O:30])[CH2:27][CH2:26]3)=[O:24])[CH2:21][CH2:20]2)[CH:14]=1.[Cl-].[Li+]>CN(C=O)C.Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:56]([C:53]1[CH:54]=[CH:55][C:50]([CH2:49][C@@:36]2([CH3:48])[N:35]3[C:31]([C:29]([NH:28][C:25]4([C:23]([NH:22][C:19]5([C:15]6[CH:14]=[CH:13][C:6]([C:5]([OH:4])=[O:7])=[CH:17][N:16]=6)[CH2:20][CH2:21]5)=[O:24])[CH2:26][CH2:27]4)=[O:30])=[CH:32][N:33]=[C:34]3[N:38]([C:39]3[CH:44]=[C:43]([Cl:45])[CH:42]=[C:41]([Cl:46])[CH:40]=3)[C:37]2=[O:47])=[CH:51][CH:52]=1)#[N:57]

Participants

8

Reactant 4

HCID 7918Acetic AnhydrideHCID 433294Lithium ChlorideHCID 2723810Sodium FormateHCID 58430957HCID 58430957, compound

Product 1

HCID 68089211HCID 68089211, compoundYield 74.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent2×

Procedure

Acetic anhydride (0.58 mL, 6.13 mmol), sodium formate (625 mg, 9.19 mmol) diisopropylethylamine (1.06 mL, 6.13 mmol) and anhydrous DMF (10 mL) were added to a 50 mL glass pressure tube. The cap was sealed and reaction allowed to stir for 30 min To this mixture was then added (R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid {1-[1-(4-iodo-pyridin-2-yl)-cyclopropylcarbamoyl]-cyclopropyl}-amide (2.35 g, 3.07 mmol) as a solution in 5 mL of anhydrous DMF, followed by lithium chloride (389 mg, 9.19 mmol) and palladium acetate (34 mg, 0.15 mmol). The mixture was capped and then allowed to stir at 80° C. in an oil bath overnight (20 h). The reaction was cooled to room temperature. The reaction was diluted with 2N HCl (15 mL) and extracted with ethyl acetate (2×20 mL). The combined organics were dried (MgSO4) and concentrated. The residual material was dissolved in DMF and purified by reversed phase HPLC using 30-100% CH3CN/H2O as gradient to afford 1.56 g of the title compound.

Workup

  1. customThe cap was sealed
  2. customreaction
  3. customThe mixture was capped
  4. stirringto stir at 80° C. in an oil bath overnight (20 h)
  5. extractionextracted with ethyl acetate (2×20 mL)
  6. dry with materialThe combined organics were dried (MgSO4)
  7. concentrationconcentrated
  8. dissolutionThe residual material was dissolved in DMF
  9. custompurified by reversed phase

Sources & evidence

ORD record
ord-34a18523d13f446cb02623954ab44446
Source dataset
uspto-grants-2013_07
Patent number
US08481750B2

Reaction notes

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