Sodium Carbonate → {2-[7-(4-carbamoyl-phenyl)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester

HRID 1272211

Reaktionsgleichung

Reaktionsgleichung von HRID 1272211
Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[C:34]([O:38][C:39]([NH:41][C:42]([CH3:62])([CH3:61])[CH2:43][C:44]1[C:52]2[C:47](=[C:48](OS(C(F)(F)F)(=O)=O)[CH:49]=[CH:50][CH:51]=2)[NH:46][CH:45]=1)=[O:40])([CH3:37])([CH3:36])[CH3:35].C(=O)([O-])[O-].[Na+].[Na+]>CS(C)=O.[Cl-].[Na+].O.C(OCC)(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:34]([O:38][C:39](=[O:40])[NH:41][C:42]([CH3:62])([CH3:61])[CH2:43][C:44]1[C:52]2[C:47](=[C:48]([C:2]3[CH:10]=[CH:9][C:5]([C:6](=[O:7])[NH2:8])=[CH:4][CH:3]=3)[CH:49]=[CH:50][CH:51]=2)[NH:46][CH:45]=1)([CH3:37])([CH3:35])[CH3:36]

Komponenten

10

Edukt 5

HCID 10340Sodium CarbonateHCID 696834-BromobenzamideHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 86595245trifluoro-methanesulfonic acid 3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl ester

Produkt 1

HCID 69517685{2-[7-(4-carbamoyl-phenyl)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl esterAusbeute 58,5 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Katalysator2×HCID 679Dimethyl SulfoxideLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A solution of 4-bromobenzamide (150 mg, 0.75 mmol), bis(pinacolato)diboron (209 mg, 0.825 mmol), potassium acetate (0.221 g, 2.25 mmol) and {1,1′-bis(diphenylphosphino)-ferrocene} dichloropalladium dichloromethane complex (18 mg, 0.0225 mmol) in dimethylsulfoxide (5 mL) is heated to 80° C. for two hours. The mixture is cooled to 20° C. and trifluoro-methanesulfonic acid 3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl ester (262 mg, 0.600 mmol), {1,1′-bis(diphenylphosphino)-ferrocene} dichloropalladium dichloromethane complex (18 mg, 0.0225 mmol) and sodium carbonate (1.9 mL, 2M, 3.75 mmol) are added. The mixture is heated to 80° C. overnight. The mixture is diluted with brine and ethyl acetate. The organic fraction is washed seven times with brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The residue is purified using silica gel chromatography (dichloromethane/10% methanol, 0.7M ammonia in dichloromethane gradient elution) to give 143 mg of {2-[7-(4-carbamoyl-phenyl)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester (58%). FDMS m/e=408 (M++1).

Aufarbeitung

  1. temperatureThe mixture is cooled to 20° C.
  2. additionare added
  3. temperatureThe mixture is heated to 80° C. overnight
  4. washThe organic fraction is washed seven times with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue is purified
  9. washsilica gel chromatography (dichloromethane/10% methanol, 0.7M ammonia in dichloromethane gradient elution)

Quellen und Nachweise

ORD-Eintrag
ord-10fa76fa0a80485497781843058e586b
Quelldatensatz
uspto-grants-2007_04
Patentnummer
US07208505B2

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