Ethyl Acetate → N-[6-chloro-5-(4-nitrophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

HRID 497689ノート

反応式

HRID 497689 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:17][C:18]1[CH:26]=[C:25]2[C:21]([C:22]([NH:35][C:36](=[O:40])[CH2:37][CH2:38][CH3:39])=[N:23][N:24]2[CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])=[CH:20][C:19]=1B1OC(C)(C)C(C)(C)O1.C(OCC)(=O)C>O.O1CCOCC1.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:17][C:18]1[CH:26]=[C:25]2[C:21]([C:22]([NH:35][C:36](=[O:40])[CH2:37][CH2:38][CH3:39])=[N:23][N:24]2[CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:32])[CH3:33])=[CH:20][C:19]=1[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1

参加物

8

反応物 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 114661-Bromo-4-nitrobenzeneHCID 22319527N-[6-chloro-5-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

生成物 1

HCID 22319608N-[6-chloro-5-(4-nitrophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide収率 115.9%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒2 回HCID 312751,4-Dioxane溶媒

実験手順

246 mg of 4-bromonitrobenzene, 1.2 g of sodium carbonate in 20 cm3 of water and 365 mg of tetrakis(triphenylphosphine)palladium are added to 2 g of N-[6-chloro-5-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 100 cm3 of dioxane. The medium is then refluxed for 20 hours and the resulting mixture is then allowed to return to room temperature and 100 cm3 of ethyl acetate and 100 cm3 of water are added. The reaction medium is filtered through a sinter funnel packed with Celite and the organic phase is separated out after settling of the phases has taken place, washed with 100 cm3 of water, with 100 cm3 of saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45° C.). The crude product is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60/μm; diameter 4 cm), eluting with a cyclohexane/ethyl acetate mixture (85/15 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). 690 mg of N-[6-chloro-5-(4-nitrophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide are obtained in the form of yellow crystals.

後処理

  1. temperatureThe medium is then refluxed for 20 hours
  2. customto return to room temperature
  3. filtrationThe reaction medium is filtered through a sinter funnel
  4. customthe organic phase is separated out
  5. washwashed with 100 cm3 of water, with 100 cm3 of saturated aqueous sodium chloride solution
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (2 kPa; 45° C.)
  9. customThe crude product is purified by chromatography under an argon pressure of 50 kPa
  10. washon a column of silica gel (particle size 40-60/μm; diameter 4 cm), eluting with a cyclohexane/ethyl acetate mixture (85/15 by volume)
  11. additionThe fractions containing the expected product
  12. customevaporated under reduced pressure (2 kPa; 50° C.)

出典と根拠

ORDレコード
ord-a22bbd3102614ef8b371505e04c8077c
出典データセット
uspto-grants-2005_09
特許番号
US06949579B2

反応ノート

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