Ethyl Acetate → N1-(cyanomethyl)-N2-{(S)-(4-fluorophenyl)[4'-(methylsulfonyl)-1,1'-biphenyl-4-yl]methyl}-L-leucinamide

HRID 1009284ノート

反応式

HRID 1009284 の反応式
[C:1]([CH2:3][NH:4][C:5](=[O:27])[C@@H:6]([NH:11][C@@H:12]([C:20]1[CH:25]=[CH:24][C:23](Br)=[CH:22][CH:21]=1)[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)[CH2:7][CH:8]([CH3:10])[CH3:9])#[N:2].[CH3:28][S:29]([C:32]1[CH:37]=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][CH:33]=1)(=[O:31])=[O:30].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C=O)C.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:1]([CH2:3][NH:4][C:5](=[O:27])[C@H:6]([CH2:7][CH:8]([CH3:10])[CH3:9])[NH:11][C@H:12]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)[C:20]1[CH:25]=[CH:24][C:23]([C:35]2[CH:36]=[CH:37][C:32]([S:29]([CH3:28])(=[O:31])=[O:30])=[CH:33][CH:34]=2)=[CH:22][CH:21]=1)#[N:2]

参加物

7

反応物 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 27595302-(4-Methanesulfonylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86590549(2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino)-4-methylpentanoic acid cyanomethylamide

生成物 1

HCID 59715505N1-(cyanomethyl)-N2-{(S)-(4-fluorophenyl)[4'-(methylsulfonyl)-1,1'-biphenyl-4-yl]methyl}-L-leucinamide

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
82.5 °C

実験手順

A mixture of (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino}-4-methylpentanoic acid cyanomethylamide (0.27 g, 0.636 mmol), 2-(4-methanesulfonylphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.177 g, 0.626 mmol) and potassium carbonate (0.703 mL of a 2.0 M solution) in DMF (5 mL) was degassed. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), dichloromethane complex (27 mg, 0.038 mmol) was added. The reaction mixture was heated in a sealed tube at 80-85° C. for 3 hours and cooled to room temperature. Ethyl acetate (15 mL) was added. The reaction mixture was washed with brine (10 mL), saturated aqueous NaHCO3 (10 mL), brine (10 mL), filtered through a plug of MgSO4/DARCO activated charcoal/silica gel, concentrated in vacuo, and purified by preparative TLC (Chromatotron® using 5% ethyl acetate/dichloromethane to elute to give N1-(cyanomethyl)-N2-{(S)-(4-fluorophenyl) [4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]methyl}-L-leucinamide.

後処理

  1. customwas degassed
  2. temperaturecooled to room temperature
  3. washThe reaction mixture was washed with brine (10 mL), saturated aqueous NaHCO3 (10 mL), brine (10 mL)
  4. filtrationfiltered through a plug of MgSO4/DARCO
  5. concentrationconcentrated in vacuo
  6. custompurified by preparative TLC (Chromatotron®
  7. washto elute

出典と根拠

ORDレコード
ord-1cf5ec6f9d3745288bc63b203126d335
出典データセット
uspto-grants-2011_07
特許番号
US07973037B2

反応ノート

読み込み中…