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

HRID 2114339Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2114339
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]

Komponenten

9

Edukt 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

Produkt 1

HCID 469412024'-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-2-biphenylcarboxamideAusbeute 47,3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

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]+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-4cf856e32a4a4adbb99c0e4079074d81
Quelldatensatz
uspto-grants-2008_10
Patentnummer
US07432258B2

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