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

HRID 1272211

反応式

HRID 1272211 の反応式
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]

参加物

10

反応物 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

生成物 1

HCID 69517685{2-[7-(4-carbamoyl-phenyl)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester収率 58.5%

試薬・触媒・溶媒 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒2 回HCID 679Dimethyl Sulfoxide溶媒HCID 8857Ethyl Acetate溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-10fa76fa0a80485497781843058e586b
出典データセット
uspto-grants-2007_04
特許番号
US07208505B2

関連ノート

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