Water → HCID 86594554, compound

HRID 1744059Notes

Reaction equation

HRID 1744059 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:5]([CH2:6][NH:7][C@@H:8]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:9]([NH:11][CH2:12][C:13]#[N:14])=[O:10])=[CH:4][CH:3]=1.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=2)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].C(=O)([O-])[O-].[Na+].[Na+].O>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:13]([CH2:12][NH:11][C:9]([C@@H:8]([NH:7][CH2:6][C:5]1[CH:19]=[CH:20][C:2]([C:37]2[CH:36]=[CH:35][C:34]([N:31]3[CH2:30][CH2:29][N:28]([C:26]([O:25][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:27])[CH2:33][CH2:32]3)=[CH:39][CH:38]=2)=[CH:3][CH:4]=1)[CH2:15][CH:16]([CH3:18])[CH3:17])=[O:10])#[N:14]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 52330144-(4-BOC-Piperazino)phenylboronic acidHCID 44403029HCID 44403029, compound

Product 1

HCID 86594554HCID 86594554, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

To (2S)-2-[(4-bromobenzyl)amino]-N-(cyanomethyl)-4-methylpentanamide (285 mg, 0.843 mmol) and 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (315 mg, 1.02 mmol) in DMF (10 mL) under dry nitrogen was added aqueous sodium carbonate (2 M, 1.3 mL, 2.53 mmol) followed by the catalyst PdCl2(dppf) (25 mg, 0.026 mmol). The reaction was heated to 95° C. for 0.5 hours and more PdCl2(dppf) (25 mg, 0.026 mmol) was added and the reaction mixture was heated overnight. Water was added and the product extracted with ether (2×), dried over Na2SO4, concentrated in vacuo, and purified by flash chromatography over silica gel (EtOAc/Hex, 4/6) to afford tert-butyl 4-(4′-{[((1S)-1-{[(cyanomethyl)amino]carbonyl}-3-methylbutyl)amino]methyl}[1,1′-biphenyl]-4-yl)-1-piperazinecarboxylate.

Workup

  1. temperaturethe reaction mixture was heated overnight
  2. extractionthe product extracted with ether (2×)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. custompurified by flash chromatography over silica gel (EtOAc/Hex, 4/6)

Sources & evidence

ORD record
ord-4fac6f9dacb34f3ba119454af9ca403c
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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