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4-(Methylthio)phenylboronic acid → N1-(cyanomethyl)-N2-{[4-(methylsulfonyl)phenyl][4'-(methylthio)-1,1'-biphenyl-4-yl]methyl}-L-leucinamide

HRID 1620904
ノート
印刷プレビュー

反応式

HRID 1620904 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:21]2[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][CH:22]=2)[NH:9][C@H:10]([C:15]([NH:17][CH2:18][C:19]#[N:20])=[O:16])[CH2:11][CH:12]([CH3:14])[CH3:13])=[CH:4][CH:3]=1.[CH3:31][S:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1>COCCOC.C(=O)([O-])[O-].[Na+].[Na+].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:19]([CH2:18][NH:17][C:15](=[O:16])[C@H:10]([CH2:11][CH:12]([CH3:14])[CH3:13])[NH:9][CH:8]([C:21]1[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][CH:22]=1)[C:5]1[CH:6]=[CH:7][C:2]([C:36]2[CH:37]=[CH:38][C:33]([S:32][CH3:31])=[CH:34][CH:35]=2)=[CH:3][CH:4]=1)#[N:20]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 2

HCID 27339594-(Methylthio)phenylboronic acidHCID 44403034N2-{(4-bromophenyl)[4-(methylsulfonyl)phenyl]methyl}-N1-(cyanomethyl)-L-leucinamide

生成物 1

HCID 86609682N1-(cyanomethyl)-N2-{[4-(methylsulfonyl)phenyl][4'-(methylthio)-1,1'-biphenyl-4-yl]methyl}-L-leucinamide

試薬・触媒・溶媒 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒
HCID 8071
1,2-Dimethoxyethane
溶媒
HCID 10340Sodium Carbonate溶媒

反応条件

温度
85 °C

実験手順

A heterogeneous mixture of N2-{(4-bromophenyl)[4-(methylsulfonyl)phenyl]methyl}-N1-(cyanomethyl)-L-leucinamide from step 4 (72 mg, 0.15 mmol), 4-(methylthio)phenylboronic acid (37 mg, 0.22 mmol) in ethylene glycol dimethyl ether (1 mL) and 2M aqueous sodium carbonate was degassed under vacuum and purged with nitrogen. To this mixture was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), dichloromethane complex (19 mg, 0.023 mmol), followed by degassing and purging with nitrogen. The reaction mixture was heated at 85° C. for 16 hours with efficient stirring. The reaction mixture was partitioned between EtOAc and aqueous NH4OAc 25% w/v. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by chromatography using EtOAc and hexane as eluant to give the title compound as a colorless gum.

後処理

  1. customwas degassed under vacuum
  2. custompurged with nitrogen
  3. customby degassing
  4. custompurging with nitrogen
  5. customThe reaction mixture was partitioned between EtOAc and aqueous NH4OAc 25%
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by chromatography

出典と根拠

ORDレコード
ord-7736f61476de4959bef1b0a2c88e0629
出典データセット
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08772336B2

反応ノート

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