Water → 6-Methyl-N-[4-(methylsulfonyl)benzyl]-2-oxo-5-propionyl-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide

HRID 1888810ノート

反応式

HRID 1888810 の反応式
I[C:2]1[CH:3]=[C:4]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][CH:25]=2)=[O:21])[C:5](=[O:19])[N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[C:7]=1[CH3:8].C(N(CC)CC)C.C([O:43][CH:44]=[CH:45][CH3:46])C.O>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[CH3:8][C:7]1[N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:16])([F:17])[F:18])[CH:10]=2)[C:5](=[O:19])[C:4]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:31])=[O:32])=[CH:26][CH:25]=2)=[O:21])=[CH:3][C:2]=1[C:44](=[O:43])[CH2:45][CH3:46]

参加物

7

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 13570Ethyl 1-propenyl etherHCID 115199335-Iodo-6-methyl-N-[4-(methylsulfonyl)benzyl]-2-oxo-1-[3-(trifluoro-methyl)phenyl]1,2-dihydropyridine-3-carboxamide

生成物 1

HCID 667253236-Methyl-N-[4-(methylsulfonyl)benzyl]-2-oxo-5-propionyl-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide収率 99.9%

試薬・触媒・溶媒 2

HCID 2724231Bis(1,2-bis(diphenylphosphino)ethane)palladium(0)触媒HCID 6228Dimethylformamide溶媒

実験手順

A solution of 5-iodo-6-methyl-N-[4-(methylsulfonyl)benzyl]-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide (Example 1 (d), 1500 mg, 2.5 mmol), bis[1,2-bis(diphenylphosphino)ethane]palladium(0) (230 mg, 0.25 mmol), triethylamine (7.5 ml, 54 mmol) and ethylpropenyl ether (900 μl, 7.5 mmol) in DMF (45 ml) was heated at 100° C. overnight. After cooling, the reaction mixture was poured into water and extracted with ethyl acetate and the solvent was removed under reduced pressure. The crude product was then dissolved in DMF (25 ml) and 2M HCl (25 ml) and then stirred for 1.5 h. The reaction mixture was then poured into aqueous NaHCO3 and extracted with ethyl acetate. The extracts were separated, evaporated under reduced pressure, and the residue was chromatographed on silica using ethyl acetate/heptane (2/1, 4/1, 10/1) as eluent. Fractions containing the product were combined and evaporated to give the title compound (1.3 g, >99%).

後処理

  1. customwas heated at 100° C. overnight
  2. temperatureAfter cooling
  3. extractionextracted with ethyl acetate
  4. customthe solvent was removed under reduced pressure
  5. dissolutionThe crude product was then dissolved in DMF (25 ml)
  6. additionThe reaction mixture was then poured into aqueous NaHCO3
  7. extractionextracted with ethyl acetate
  8. customThe extracts were separated
  9. customevaporated under reduced pressure
  10. customthe residue was chromatographed on silica
  11. additionFractions containing the product
  12. customevaporated

出典と根拠

ORDレコード
ord-b7443b4b85084fd2a324d45aa8124fa5
出典データセット
uspto-grants-2013_08
特許番号
US08501784B2

反応ノート

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