Water → HCID 22236145, compound

HRID 1744054Notes

Reaction equation

HRID 1744054 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][CH:9]([CH2:16][CH:17]([CH3:19])[CH3:18])[C:10]([NH:12][CH2:13][C:14]#[N:15])=[O:11])=[N:6][CH:7]=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:14]([CH2:13][NH:12][C:10]([CH:9]([NH:8][C:5]1[N:4]=[CH:3][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:7][N:6]=1)[CH2:16][CH:17]([CH3:19])[CH3:18])=[O:11])#[N:15]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 52330144-(4-BOC-Piperazino)phenylboronic acidHCID 22235943HCID 22235943, compound

Product 1

HCID 22236145HCID 22236145, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

To 2-[(5-bromo-2-pyrimidinyl)amino]-N-(cyanomethyl)-4-methylpentanamide (123 mg, 0.377 mmol) and 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (140 mg, 0.453 mmol) in DMF (10 mL) under dry nitrogen was added aqueous sodium carbonate (2 M, 0.6 mL, 1.2 mmol) followed by the catalyst PdCl2(dppf) (15 mg, 0.0113 mmol). The reaction was heated to 90° C. for 0.5 hours and more PdCl2(dppf) (15 mg, 0.0113 mmol) was added and the reaction mixture was heated for another 5.5 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, 7/3) to afford tert-butyl 4-(4-{2-[(1-{[(cyanomethyl)amino]carbonyl}-3-methylbutyl)amino]-5-pyrimidinyl}phenyl)-1-piperazinecarboxylate.

Workup

  1. temperaturethe reaction mixture was heated for another 5.5 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, 7/3)

Sources & evidence

ORD record
ord-82f9b3ba0cb745bf866b5fd563b128c7
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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