Ethyl Acetate → N1-[1-(4'-chloro-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N2-(3,4-dichlorophenyl)-N1,N2-dimethylglycinamide

HRID 2114336노트

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HRID 2114336 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.[Cl:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.C([O-])([O-])=O.[Na+].[Na+].C(OCC)(=O)C>O1CCOCC1.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:30][C:31]1[CH:36]=[CH:35][C:34]([C:2]2[CH:3]=[CH:4][C:5]([CH:8]([N:15]([CH3:29])[C:16](=[O:28])[CH2:17][N:18]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=3)[CH3:19])[CH2:9][N:10]3[CH2:11][CH2:12][CH2:13][CH2:14]3)=[CH:6][CH:7]=2)=[CH:33][CH:32]=1

참가 물질

9

반응물 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 59809676N1-[1-(4-bromophenyl)-2-(1-pyrrolidinyl)ethyl]-N2-(3,4-dichlorophenyl)-N1,N2-dimethylglycinamide

생성물 1

HCID 59809655N1-[1-(4'-chloro-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N2-(3,4-dichlorophenyl)-N1,N2-dimethylglycinamide수율 47.1%

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매HCID 57417360Sodium chloride; water용매

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온도
185 °C

실험 절차

N1-[1-(4-bromophenyl)-2-(1-pyrrolidinyl)ethyl]-N2-(3,4-dichlorophenyl)-N1,N2-dimethylglycinamide (50 mg, 0.100 mmol) was dissolved in 500 uL of 1,4-Dioxane and combined with (4-chlorophenyl)boronic acid (23 mg, 0.150 mmol), Pd(dppf)2Cl2 (2 mg, 0.003 mmol), and 300 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 185° C. for 360 seconds. Ethyl acetate (2 mL) and brine (2 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 25 mg (47%) of the title compound as a tan solid. MS (ES) m/e 530/532 [M+H]+.

후처리

  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. filtrationthe reaction mixture was filtered
  7. customThe organic layer was separated
  8. customthe solvent was removed under reduced pressure
  9. dissolutionThe residue was dissolved in 1.0 mL DMSO
  10. custompurified by preparative HPLC (Phenomenex 75×30 mm column, 40 mL/min flow rate

출처 및 근거

ORD 기록
ord-5e70262193ef48e1a658b03844b87aba
출처 데이터셋
uspto-grants-2008_10
특허 번호
US07432258B2

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