Dichloromethane → 5-(3-acetyl-6-cyano-2-ethoxy-5-methylphenyl)-N,N-dimethylpyridine-2-carboxamide

HRID 1499903노트

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HRID 1499903 반응식
C(=O)([O-])[O-].[Na+].[Na+].[C:7]([C:10]1[CH:17]=[C:16]([CH3:18])[C:13]([C:14]#[N:15])=[C:12](I)[C:11]=1[O:20][CH2:21][CH3:22])(=[O:9])[CH3:8].[CH3:23][N:24]([CH3:36])[C:25]([C:27]1[N:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)=[O:26].ClCCl>O.C(#N)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:7]([C:10]1[C:11]([O:20][CH2:21][CH3:22])=[C:12]([C:30]2[CH:29]=[CH:28][C:27]([C:25]([N:24]([CH3:36])[CH3:23])=[O:26])=[N:32][CH:31]=2)[C:13]([C:14]#[N:15])=[C:16]([CH3:18])[CH:17]=1)(=[O:9])[CH3:8]

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 53438177[6-(Dimethylcarbamoyl)pyridin-3-yl]boronic acidHCID 866778254-Acetyl-3-ethoxy-2-iodo-6-methylbenzonitrile

생성물 1

HCID 866778265-(3-acetyl-6-cyano-2-ethoxy-5-methylphenyl)-N,N-dimethylpyridine-2-carboxamide수율 75%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6342Acetonitrile용매

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온도
100 °C

실험 절차

Sodium carbonate (3 g, 30 mmol) in water (20 mL) was added to a mixture of 4-acetyl-3-ethoxy-2-iodo-6-methylbenzonitrile (3 g, 9 mmol) and {6-[(dimethylamino)carbonyl]pyridin-3-yl}boronic acid (1700 mg, 8.8 mmol, Example 313, Step 2) in acetonitrile (100 mL). The mixture was degassed with nitrogen and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (400 mg, 0.4 mmol) was added. The reaction was degassed again with nitrogen and was heated to 100° C. for 4 hrs. The reaction was allowed to cool to room temperature, diluted with water and extracted with EtOAc. The combined organic layer was washed with brine, dried over MgSO4, filtered and concentrated to give the crude product. The product was purified by FCC on silica gel eluting (hexane/EtOAc, 0-100%) gradient to give 5-(3-acetyl-6-cyano-2-ethoxy-5-methylphenyl)-N,N-dimethylpyridine-2-carboxamide product as yellow solid (2.3 g, 75%). LCMS calculated for C20H22N3O3(M+H)+: m/z=352.1; found: 352.2.

후처리

  1. additionwas added
  2. customThe reaction was degassed again with nitrogen
  3. temperatureto cool to room temperature
  4. additiondiluted with water
  5. extractionextracted with EtOAc
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give the crude product
  11. customThe product was purified by FCC on silica gel eluting (hexane/EtOAc, 0-100%) gradient

출처 및 근거

ORD 기록
ord-04680ddd7c784b08822bee3e40680eb1
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09199982B2

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