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

HRID 1365711

반응식

HRID 1365711 반응식
[CH3:1][O:2][C:3](=[O:19])[C@@H:4]([NH:8][C:9](=[O:18])[C:10]1[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=1[Cl:17])[CH2:5][CH:6]=[CH2:7].I[C:21]1[CH:26]=[CH:25][C:24]([N:27]([CH:34]([CH3:36])[CH3:35])[C:28]2[N:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[CH3:1][O:2][C:3](=[O:19])[C@@H:4]([NH:8][C:9](=[O:18])[C:10]1[C:11]([Cl:17])=[CH:12][CH:13]=[CH:14][C:15]=1[Cl:16])[CH2:5]/[CH:6]=[CH:7]/[C:21]1[CH:26]=[CH:25][C:24]([N:27]([CH:34]([CH3:36])[CH3:35])[C:28]2[N:29]=[CH:30][CH:31]=[CH:32][N:33]=2)=[CH:23][CH:22]=1

참가 물질

8

반응물 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 57762562(S)-2-(2,6-dichlorobenzamido)pent-4-enoic acid methyl esterHCID 57762606N-(4-iodophenyl)-N-isopropylpyrimidin-2-amine

생성물 1

HCID 57762568(S,E)-2-(2,6-dichlorobenzamido)-5-[4-(isopropyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester수율 63.3%

시약·촉매·용매 3

HCID 80271Tri-o-tolylphosphine촉매HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

Under an argon atmosphere, palladium acetate (19.9 mg) and tris(2-methylphenyl)phosphine (25.9 mg) were added to a suspension of (S)-2-(2,6-dichlorobenzamido)pent-4-enoic acid methyl ester (514.4 mg), N-(4-iodophenyl)-N-isopropylpyrimidin-2-amine (577.4 mg) and potassium carbonate (352.9 mg) in DMF (6 ml), and the resulting mixture was stirred at 80° C. for 7 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 layer 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=2/1→1/1→1/3). The obtained crudely purified product was purified again by column chromatography (silica gel, eluent: cyclohexane/ethyl acetate=6/1→4/1→2/1) to obtain (S,E)-2-(2,6-dichlorobenzamido)-5-[4-(isopropyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester (553.6 mg).

후처리

  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 layer 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=2/1→1/1→1/3)
  8. customThe obtained crudely purified product
  9. customwas purified again by column chromatography (silica gel, eluent: cyclohexane/ethyl acetate=6/1→4/1→2/1)

출처 및 근거

ORD 기록
ord-82cb87fef33546bcab3eb0ecb5845bd1
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07893046B2

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