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

HRID 2114339Notes

Reaction equation

HRID 2114339 reaction equation
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]

Participants

9

Reactant 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

Product 1

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

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-4cf856e32a4a4adbb99c0e4079074d81
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

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