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Potassium Carbonate → Tert-butyl[1-(5-chloro-4-cyano-3-{6-[(dimethylamino)carbonyl]pyridin-3-yl}-2-ethoxyphenyl)ethyl]carbamate

HRID 510979
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HRID 510979 반응식
Br[C:2]1[C:3]([O:21][CH2:22][CH3:23])=[C:4]([CH:11]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH3:12])[CH:5]=[C:6]([Cl:10])[C:7]=1[C:8]#[N:9].[CH3:24][N:25]([CH3:37])[C:26]([C:28]1[N:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1)=[O:27].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:10][C:6]1[C:7]([C:8]#[N:9])=[C:2]([C:31]2[CH:32]=[N:33][C:28]([C:26]([N:25]([CH3:37])[CH3:24])=[O:27])=[CH:29][CH:30]=2)[C:3]([O:21][CH2:22][CH3:23])=[C:4]([CH:11]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH3:12])[CH:5]=1
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참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 53438177[6-(Dimethylcarbamoyl)pyridin-3-yl]boronic acidHCID 123418761Tert-butyl[1-(3-bromo-5-chloro-4-cyano-2-ethoxyphenyl)ethyl]carbamate

생성물 1

HCID 88540918Tert-butyl[1-(5-chloro-4-cyano-3-{6-[(dimethylamino)carbonyl]pyridin-3-yl}-2-ethoxyphenyl)ethyl]carbamate수율 84.6%

시약·촉매·용매 3

HCID 178418397
HCID 178418397, 화합물
촉매
HCID 962Water용매
HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

The tert-butyl [1-(3-bromo-5-chloro-4-cyano-2-ethoxyphenyl)ethyl]carbamate (0.05 g, 0.1 mmol, Example 179, peak 2) was combined with {6-[(dimethylamino)carbonyl]pyridin-3-yl}boronic acid (0.034 g, 0.17 mmol, Example 179, Step 5) in 1,4-dioxane (3.0 mL) and potassium carbonate (0.034 g, 0.25 mmol) dissolved in water (1.0 mL) in a tube. The reaction was degassed with nitrogen and the tetrakis(triphenylphosphine)palladium(0) (0.03 g, 0.02 mmol) was added and degassed again. The tube was sealed and heated in an oil bath to 90° C. After heating for 18 h the reaction was complete. This was allowed to cool to room temperature and partitioned between EtOAc and water. The organic layer was washed with brine, dried over magnesium sulfate and concentrated to give the crude as a dark oil. The product was purified by chromatography on silica gel eluting with hexane:EtOAc gradient to give tert-butyl [1-(5-chloro-4-cyano-3-{6-[(dimethylamino)carbonyl]pyridin-3-yl}-2-ethoxyphenyl)ethyl]carbamate as a viscous oil (0.04 g, 66%). LCMS calculated for C24H30ClN4O4 (M+H)+: m/z=473.2. found: 473.1.

후처리

  1. customThe reaction was degassed with nitrogen
  2. customdegassed again
  3. customThe tube was sealed
  4. temperatureAfter heating for 18 h the reaction
  5. temperatureto cool to room temperature
  6. custompartitioned between EtOAc and water
  7. washThe organic layer was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customto give the crude as a dark oil
  11. customThe product was purified by chromatography on silica gel eluting with hexane

출처 및 근거

ORD 기록
ord-77bac3aa11eb45c599734e8a28d5b3a5
출처 데이터셋
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09096600B2

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