Water → HCID 69151040, compound

HRID 1744132Notes

Reaction equation

HRID 1744132 reaction equation
Br[C:2]1[C:3]([NH:14][C@H:15]([C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)=[O:21])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:4][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH:6]=1.[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][N:42]([C:45]2[CH:50]=[CH:49][C:48](B(O)O)=[CH:47][CH:46]=2)[CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].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:10]([O:9][C:7]([N:5]1[CH:6]=[C:2]([C:48]2[CH:47]=[CH:46][C:45]([N:42]3[CH2:41][CH2:40][N:39]([C:37]([O:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:38])[CH2:44][CH2:43]3)=[CH:50][CH:49]=2)[C:3]([NH:14][C@H:15]([C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)=[O:21])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:4]1)=[O:8])([CH3:13])([CH3:12])[CH3:11]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 52330144-(4-BOC-Piperazino)phenylboronic acidHCID 691517634-methoxybenzyl N-[4-bromo-1-(tert-butoxycarbonyl)-1H-pyrazol-3-yl]leucinate

Product 1

HCID 69151040HCID 69151040, 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 4-methoxybenzyl N-[4-bromo-1-(tert-butoxycarbonyl)-1H-pyrazol-3-yl]leucinate (1.45 g, 2.92 mmol), 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (1.117 g, 3.65 mmol, prepared as described in Example 1) and catalyst PdCl2(dppf) (75 mg, 0.09 mmol) in DMF (30 mL) under dry nitrogen was added aqueous sodium carbonate (2.0 M, 3.3 mL, 6.6 mmol). The reaction was heated to 90° C. for 0.5 hour and an additional aliquot of PdCl2(dppf) (20 mg, 0.022 mmol) was added and the reaction mixture was heated for 1½ hour. 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, 25/75) to afford 4-methoxybenzyl N-(1-(tert-butoxycarbonyl)-4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-1H-pyrazol-3-yl)leucinate.

Workup

  1. temperaturethe reaction mixture was heated for 1½ hour
  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, 25/75)

Sources & evidence

ORD record
ord-c849a78007c04c7eb8f4859a470a08a7
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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