Potassium Iodide → HCID 86724038, compound

HRID 1475510Notes

Reaction equation

HRID 1475510 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14]Cl)[N:11]([CH2:16][C:17]([N:19]2[C:27]3[CH:26]=[C:25]([CH2:28][C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=4[F:36])[N:24]=[CH:23][C:22]=3[C:21]([CH3:38])([CH3:37])[CH2:20]2)=[O:18])[CH2:10][C@H:9]1[CH3:39])=[O:7])([CH3:4])([CH3:3])[CH3:2].[I-].[K+].C(=O)([O-])[O-].[K+].[K+].[NH:48]1[CH:53]=[CH:52][CH:51]=[N:50][C:49]1=[O:54]>C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14][N:50]2[CH:51]=[CH:52][CH:53]=[N:48][C:49]2=[O:54])[N:11]([CH2:16][C:17]([N:19]2[C:27]3[CH:26]=[C:25]([CH2:28][C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=4[F:36])[N:24]=[CH:23][C:22]=3[C:21]([CH3:38])([CH3:37])[CH2:20]2)=[O:18])[CH2:10][C@H:9]1[CH3:39])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 684012(1H)-PyrimidinoneHCID 86724033(2R,5R)-5-Chloromethyl-4-{2-[6-(2,4-difluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-c]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 86724038HCID 86724038, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of (2R,5R)-5-chloromethyl-4-{2-[6-(2,4-difluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-c]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (124 mg, 0.23 mmol), potassium iodide (83 mg, 0.5 mmol), anhydrous potassium carbonate (276 mg, 2.0 mmol) and 1H-pyrimidin-2-one (48 mg, 0.5 mmol) in acetonitrile (5 mL) was stirred and held at reflux in a sealed tube for 16 hours. Upon cooling to room temperature the solvent was removed in vacuo and the residues partitioned between DCM and water. The organic layer was separated, the solvent removed in vacuo and the residues were purified by column chromatography (silica, elution with 30-100% ethyl acetate in petroleum ether then 0-50% methanol in ethyl acetate) to give (2R,5S)-4-{2-[6-(2,4-difluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-c]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-5-(2-oxo-2H-pyrimidin-1-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (70 mg, 49%) as a colourless solid. MS: [M+H]+=623. Compounds of Table 7 below were prepared using procedures analogous to that described in General Procedure 6 above, by reaction of the appropriate nucleophile with the appropriate substituted halopiperazine-amide (synthesised as described above, Preparation reference number given).

Workup

  1. temperatureat reflux in a sealed tube for 16 hours
  2. customwas removed in vacuo
  3. customthe residues partitioned between DCM and water
  4. customThe organic layer was separated
  5. customthe solvent removed in vacuo
  6. customthe residues were purified by column chromatography (
  7. washsilica, elution with 30-100% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-e49a8faa92ce43f0bf93eb74afedb1c0
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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