Dichloromethane → Tert-butyl 4-{4'-[(1-{[(cyanomethyl)amino]carbonyl}-3-methylbutoxy)methyl][1,1'-biphenyl]-4-yl}-1-piperazinecarboxylate

HRID 1744069Notes

Reaction equation

HRID 1744069 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:5]([CH2:6][O:7][CH: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+].ClCCl>CN(C=O)C.C(OC(=O)C)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]([CH:8]([O: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

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 52330144-(4-BOC-Piperazino)phenylboronic acidHCID 222359802-[(4-bromobenzyl)oxy]-N-(cyanomethyl)-4-methylpentanamide

Product 1

HCID 22235855Tert-butyl 4-{4'-[(1-{[(cyanomethyl)amino]carbonyl}-3-methylbutoxy)methyl][1,1'-biphenyl]-4-yl}-1-piperazinecarboxylate

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To 2-[(4-bromobenzyl)oxy]-N-(cyanomethyl)-4-methylpentanamide (646 mg, 1.9 mmoles) in DMF (12.5 mL) was added 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (640 mg, 2.1 mmoles) followed by 2 M aqueous sodium carbonate (2.85 mL, 5.7 mmoles) and finally [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (78 mg, 0.1 mmoles). The reaction was stirred overnight at 85° C. and cooled to room temperature prior to taking it up in ethylacetate. The organic phase was washed three times with 1.2 N hydrochloric acid, washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography (10% EtOAc, 90% Hexanes) to give tert-butyl 4-{4′-[(1-{[(cyanomethyl)amino]carbonyl}-3-methylbutoxy)-methyl][1,1 ′-biphenyl]-4-yl}-1-piperazinecarboxylate.

Workup

  1. temperaturecooled to room temperature
  2. washThe organic phase was washed three times with 1.2 N hydrochloric acid
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by chromatography (10% EtOAc, 90% Hexanes)

Sources & evidence

ORD record
ord-11ce43679b7942799cdd19db158db7d9
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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