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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 2223509
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HRID 2223509 반응식
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]
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참가 물질

6

반응물 2

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

생성물 1

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

시약·촉매·용매 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매
HCID 8071
1,2-Dimethoxyethane
용매
HCID 10340Sodium Carbonate용매

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온도
85 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-7a6d6c1918864a66942dd2ba91587203
출처 데이터셋
uspto-grants-2008_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07375134B2

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