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

HRID 1620904Notes

Reaction equation

HRID 1620904 reaction equation
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]

Participants

6

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
85 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-7736f61476de4959bef1b0a2c88e0629
Source dataset
uspto-grants-2014_07
Patent number
US08772336B2

Reaction notes

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