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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
ノート
印刷プレビュー

反応式

HRID 510979 の反応式
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
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418397
HCID 178418397、化合物
触媒
HCID 962Water溶媒
HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-77bac3aa11eb45c599734e8a28d5b3a5
出典データセット
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09096600B2

反応ノート

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