Sodium Carbonate → N1-[1-[4'-(acetylamino)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N2-(3,4-dichlorophenyl)-N1-methyl-N2-[2-(methyloxy)ethyl]glycinamide

HRID 2114426Notes

Reaction equation

HRID 2114426 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:15]([CH3:32])[C:16](=[O:31])[CH2:17][N:18]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=2)[CH2:19][CH2:20][O:21][CH3:22])[CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[C:33]([NH:36][C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1)(=[O:35])[CH3:34].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.CS(C)=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]>[C:33]([NH:36][C:37]1[CH:42]=[CH:41][C:40]([C:2]2[CH:3]=[CH:4][C:5]([CH:8]([N:15]([CH3:32])[C:16](=[O:31])[CH2:17][N:18]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=3)[CH2:19][CH2:20][O:21][CH3:22])[CH2:9][N:10]3[CH2:14][CH2:13][CH2:12][CH2:11]3)=[CH:6][CH:7]=2)=[CH:39][CH:38]=1)(=[O:35])[CH3:34]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27346574-Acetamidophenylboronic acidHCID 59809653N1-[1-(4-bromophenyl)-2-(1-pyrrolidinyl)ethyl]-N2-(3,4-dichlorophenyl)-N1-methyl-N2-[2-(methyloxy)ethyl]glycinamide

Product 1

HCID 59809636N1-[1-[4'-(acetylamino)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N2-(3,4-dichlorophenyl)-N1-methyl-N2-[2-(methyloxy)ethyl]glycinamideYield 28.9%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
160 °C

Procedure

N1-[1-(4-bromophenyl)-2-(1-pyrrolidinyl)ethyl]-N2-(3,4-dichlorophenyl)-N1-methyl-N2-[2-(methyloxy)ethyl]glycinamide (150 mg, 0.276 mmol) was dissolved in 1 mL of 1,4-dioxane and combined with [4-(acetylamino)phenyl]boronic acid (74 mg, 0.413 mmol), Pd(dppf)2Cl2 (6.8 mg, 0.008 mmol), and 825 uL of 1M Na2CO3 in water in a glass reaction tube (0.5-2.0 mL Smith Process Vial) that was equipped with a magnetic stir bar. The tube was fitted with a rubber septum and hermetically sealed with a crimped metal foil seal. Using a Personal Chemistry Emrys Optimizer microwave unit, the reaction mixture was magnetically stirred and irradiated with microwave energy of dynamically adjusted power in order to maintain a temperature of 160° C. for 360 seconds. The reaction mixture was diluted with 2 mL of DMSO and filtered through a 0.2 micron PTFE filter and purified by preparative HPLC (Waters C18RP Xterra 5 micron 50×100 mm column, 45 mL/min flow rate, A: 0.1% TFA in acetonitrile B: 0.1% TFA in water, A: 10 to 95% over 20 min, UV detection at 215 nm) to give 47.7 mg (19%) of the title compound as a brown solid. MS (ES) m/e 598, 600 [M+H]+.

Workup

  1. customwas equipped with a magnetic stir bar
  2. customThe tube was fitted with a rubber septum
  3. customhermetically sealed with a crimped metal foil
  4. customseal
  5. customirradiated with microwave energy of dynamically adjusted power in order
  6. filtrationfiltered through a 0.2 micron PTFE
  7. filtrationfilter
  8. custompurified by preparative HPLC (Waters C18RP Xterra 5 micron 50×100 mm column, 45 mL/min flow rate

Sources & evidence

ORD record
ord-4372031b700e4abab8b2165e06389266
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

Loading…