Ethyl Acetate → 4'-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-2-biphenylcarboxamide

HRID 2114339노트

반응식

HRID 2114339 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:15]([CH3:29])[C:16](=[O:28])[CH2:17][N:18]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[CH3:19])[CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[NH2:30][C:31]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1B(O)O)=[O:32].C([O-])([O-])=O.[Na+].[Na+].C(OCC)(=O)C>CN(C=O)C.O.[Cl-].[Na+].O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:27][C:22]1[CH:21]=[C:20]([N:18]([CH3:19])[CH2:17][C:16]([N:15]([CH3:29])[CH:8]([C:5]2[CH:6]=[CH:7][C:2]([C:34]3[C:33]([C:31]([NH2:30])=[O:32])=[CH:38][CH:37]=[CH:36][CH:35]=3)=[CH:3][CH:4]=2)[CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[O:28])[CH:25]=[CH:24][C:23]=1[Cl:26]

참가 물질

9

반응물 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 2737809(2-Aminocarbonylphenyl)boronic acidHCID 59809676N1-[1-(4-bromophenyl)-2-(1-pyrrolidinyl)ethyl]-N2-(3,4-dichlorophenyl)-N1,N2-dimethylglycinamide

생성물 1

HCID 469412024'-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-2-biphenylcarboxamide수율 47.3%

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 57417360Sodium chloride; water용매

반응 조건

온도
80 °C

실험 절차

N1-[1-(4-bromophenyl)-2-(1-pyrrolidinyl)ethyl]-N2-(3,4-dichlorophenyl)-N1,N2-dimethylglycinamide (100 mg, 0.200 mmol) was dissolved in 1.5 mL of DMF and combined with [2-(aminocarbonyl)phenyl]boronic acid (40 mg, 0.240 mmol), Pd(dppf)2Cl2 (8 mg, 0.01 mmol), and 400 uL of 2M Na2CO3 in water. The reaction mixture was heated to at 80° C. and stirred for 18 h. Ethyl acetate (4 mL) and brine (4 mL) were added and the reaction mixture was filtered. The organic layer was separated and the solvent was removed under reduced pressure. The residue was dissolved in 1.0 mL DMSO and purified by preparative HPLC (Phenomenex 75×30 mm column, 40 mL/min flow rate, A: 0.1% TFA in acetonitrile B: 0.1% TFA in water, A: 10 to 100% over 15 min, UV detection at 215 nm) to give 51 mg (47%) of the title compound as a yellow solid. MS (ES) m/e 539/541 [M+H]+.

후처리

  1. filtrationthe reaction mixture was filtered
  2. customThe organic layer was separated
  3. customthe solvent was removed under reduced pressure
  4. dissolutionThe residue was dissolved in 1.0 mL DMSO
  5. custompurified by preparative HPLC (Phenomenex 75×30 mm column, 40 mL/min flow rate
  6. waitA: 0.1% TFA in acetonitrile B: 0.1% TFA in water, A: 10 to 100% over 15 min

출처 및 근거

ORD 기록
ord-4cf856e32a4a4adbb99c0e4079074d81
출처 데이터셋
uspto-grants-2008_10
특허 번호
US07432258B2

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