Potassium Iodide → HCID 86724038、化合物

HRID 1475510

反応式

HRID 1475510 の反応式
[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]

参加物

6

反応物 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

生成物 1

HCID 86724038HCID 86724038、化合物収率 49%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-e49a8faa92ce43f0bf93eb74afedb1c0
出典データセット
uspto-grants-2015_04
特許番号
US09018214B2

関連ノート

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