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

HRID 2114339ノート

反応式

HRID 2114339 の反応式
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]

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
80 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-4cf856e32a4a4adbb99c0e4079074d81
出典データセット
uspto-grants-2008_10
特許番号
US07432258B2

反応ノート

読み込み中…