Water → HCID 86594552, compound

HRID 1744049Notes

Reaction equation

HRID 1744049 reaction equation
Br[C:2]1[CH:19]=[CH:18][C:5]([NH:6][C@@H:7]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:8]([NH:10][CH2:11][C:12]#[N:13])=[O:9])=[CH:4][CH:3]=1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].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:12]([CH2:11][NH:10][C:8]([C@@H:7]([NH:6][C:5]1[CH:18]=[CH:19][C:2]([C:36]2[CH:35]=[CH:34][C:33]([N:30]3[CH2:29][CH2:28][N:27]([C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])[CH2:32][CH2:31]3)=[CH:38][CH:37]=2)=[CH:3][CH:4]=1)[CH2:14][CH:15]([CH3:17])[CH3:16])=[O:9])#[N:13]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 52330144-(4-BOC-Piperazino)phenylboronic acidHCID 86594551HCID 86594551, compound

Product 1

HCID 86594552HCID 86594552, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
105 °C

Procedure

To (2S)-2-(4-bromoanilino)-N-(cyanomethyl)-4-methylpentanamide (555 mg, 1.71 mmol), and 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (520 mg, 1.71 mmol) in DMF (20 mL) under dry nitrogen was added aqueous sodium carbonate (2 M, 2.55 mL, 5.13 mmol) followed by the catalyst PdCl2(dppf) (42 mg, 0.051 mmol). The reaction was heated to 105° C. for 0.75 hours and more PdCl2(dppf) (42 mg, 0.051 mmol) was added and the reaction mixture was heated for another 4–5 hours. 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 then 1/1) to afford tert-butyl 4-{4′-[((1S)-1-{[(cyanomethyl)amino]carbonyl}-3-methylbutyl)amino][1,1′-biphenyl]-4-yl}-1-piperazinecarboxylate.

Workup

  1. temperaturethe reaction mixture was heated for another 4–5 hours
  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-6ab4f7a2e247469782745b72b4549539
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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