Toluene → Tert-butyl 2-(2-(benzyloxy)-5-(methyl(2-(morpholin-4-yl)ethyl)amino)benzamido)-4-phenylbenzoate

HRID 454610

반응식

HRID 454610 반응식
[CH3:1][NH:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1.[CH2:26]([O:33][C:34]1[CH:61]=[CH:60][C:59](Br)=[CH:58][C:35]=1[C:36]([NH:38][C:39]1[CH:51]=[C:50]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[CH:49]=[CH:48][C:40]=1[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])=[O:37])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(Cl)(Cl)Cl.O>[CH2:26]([O:33][C:34]1[CH:61]=[CH:60][C:59]([N:2]([CH3:1])[CH2:3][CH2:4][N:5]2[CH2:10][CH2:9][O:8][CH2:7][CH2:6]2)=[CH:58][C:35]=1[C:36]([NH:38][C:39]1[CH:51]=[C:50]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[CH:49]=[CH:48][C:40]=1[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])=[O:37])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

참가 물질

10

반응물 4

HCID 1140TolueneHCID 62657Potassium Phosphate, Tribasic2회HCID 14979282Methyl(2-(morpholin-4-yl)ethyl)amine2회HCID 66990333Tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate

생성물 1

HCID 66990678Tert-butyl 2-(2-(benzyloxy)-5-(methyl(2-(morpholin-4-yl)ethyl)amino)benzamido)-4-phenylbenzoate수율 71.9%

시약·촉매·용매 5

HCID 167845palladium(II) acetate촉매2회HCID 9811564Bis(dibenzylideneacetone)palladium촉매2회HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl촉매2회HCID 962Water용매HCID 6212Chloroform용매

실험 절차

N-Methyl-2-(morpholin-4-yl)ethylamine (0.097 g), tripotassium phosphate (0.17 g), tris(dibenzylideneacetone)dipalladium(0) (2.5 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (6.4 mg), and palladium(II) acetate (1.2 mg) were added to a toluene (2.3 mL) solution of tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate (0.15 g), followed by heating to reflux under a nitrogen atmosphere for 1 hour and 30 minutes. The reaction mixture was cooled to room temperature, and then N-methyl-2-(morpholin-4-yl)ethylamine (0.019 g), tripotassium phosphate (0.029 g), tris(dibenzylideneacetone)dipalladium(0) (2.5 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (6.4 mg) and palladium(II) acetate (1.2 mg) were added to the reaction mixture, followed by heating to reflux under a nitrogen atmosphere for 6 hours. The reaction mixture was cooled to room temperature, and then water and chloroform were added thereto. The insoluble substance was removed by filtration. The organic layer was separated and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 100-90% chloroform/methanol] to obtain 0.12 g of tert-butyl 2-(2-(benzyloxy)-5-(methyl(2-(morpholin-4-yl)ethyl)amino)benzamido)-4-phenylbenzoate.

후처리

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 1 hour and 30 minutes
  3. temperatureby heating
  4. temperatureto reflux under a nitrogen atmosphere for 6 hours
  5. temperatureThe reaction mixture was cooled to room temperature
  6. customThe insoluble substance was removed by filtration
  7. customThe organic layer was separated
  8. dry with materialdried over anhydrous sodium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 100-90% chloroform/methanol]

출처 및 근거

ORD 기록
ord-7c23642f12df40259d96040db23b558e
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08492582B2

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