Potassium Carbonate → (S,E)-2-(2,6-dichlorobenzamido)-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester

HRID 230371

反応式

HRID 230371 の反応式
CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH3:23][O:24][C:25](=[O:41])[C@@H:26]([NH:30][C:31](=[O:40])[C:32]1[C:37]([Cl:38])=[CH:36][CH:35]=[CH:34][C:33]=1[Cl:39])[CH2:27][CH:28]=[CH2:29].I[C:43]1[CH:48]=[CH:47][C:46]([N:49]([CH3:56])[C:50]2[N:55]=[CH:54][CH:53]=[CH:52][N:51]=2)=[CH:45][CH:44]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C>[CH3:23][O:24][C:25](=[O:41])[C@@H:26]([NH:30][C:31](=[O:40])[C:32]1[C:33]([Cl:39])=[CH:34][CH:35]=[CH:36][C:37]=1[Cl:38])[CH2:27]/[CH:28]=[CH:29]/[C:43]1[CH:48]=[CH:47][C:46]([N:49]([CH3:56])[C:50]2[N:51]=[CH:52][CH:53]=[CH:54][N:55]=2)=[CH:45][CH:44]=1

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 80271Tri-o-tolylphosphineHCID 46184395HCID 46184395、化合物HCID 57762562(S)-2-(2,6-dichlorobenzamido)pent-4-enoic acid methyl ester

生成物 1

HCID 57762554(S,E)-2-(2,6-dichlorobenzamido)-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester収率 66.4%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

Under an argon atmosphere, palladium acetate (93.2 mg) and tris(2-methylphenyl)phosphine (121.2 mg) were added to a suspension of (S)-2-(2,6-dichlorobenzamido)pent-4-enoic acid methyl ester (1.20 g), N-(4-iodophenyl)-N-methylpyrimidin-2-amine (1.24 g) and potassium carbonate (824 mg) in DMF (20 ml), and the resulting mixture was stirred at 80° C. for 3 hours. After cooling the reaction solution to room temperature, ethyl acetate was added thereto, and the resulting mixture was washed twice with water and once with saturated brine, followed by drying the organic layers over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated. The residue was purified by column chromatography (silica gel, eluent: cyclohexane/chloroform=1/1→chloroform). The obtained crudely purified product was purified again by column chromatography (silica gel, eluent: cyclohexane/ethyl acetate=4/1→2/1) to obtain (S,E)-2-(2,6-dichlorobenzamido)-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester (1.28 g).

後処理

  1. temperatureAfter cooling the reaction solution to room temperature
  2. washthe resulting mixture was washed twice with water and once with saturated brine
  3. dry with materialby drying the organic layers over anhydrous sodium sulfate
  4. customAfter removing anhydrous sodium sulfate
  5. filtrationby filtration
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified by column chromatography (silica gel, eluent: cyclohexane/chloroform=1/1→chloroform)
  8. customThe obtained crudely purified product
  9. customwas purified again by column chromatography (silica gel, eluent: cyclohexane/ethyl acetate=4/1→2/1)

出典と根拠

ORDレコード
ord-4410d50445e34c7d95dbee0e1a452803
出典データセット
uspto-grants-2009_07
特許番号
US07566724B2

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