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

HRID 1744064Notes

Reaction equation

HRID 1744064 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[O:5][CH:6]([CH2:13][CH:14]([CH3:16])[CH3:15])[C:7]([NH:9][CH2:10][C:11]#[N:12])=[O:8].[CH:20]([Si:23]([CH:45]([CH3:47])[CH3:46])([CH:42]([CH3:44])[CH3:43])[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])([CH3:22])[CH3:21].C(=O)([O-])[O-].[K+].[K+].ClCCl>C1(C)C=CC=CC=1.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:11]([CH2:10][NH:9][C:7]([CH:6]([O:5][C:4]1[CH:3]=[C:2]([C:36]2[CH:35]=[CH:34][C:33]([N:30]3[CH2:31][CH2:32][N:27]([C:25]([O:24][Si:23]([CH:42]([CH3:44])[CH3:43])([CH:45]([CH3:47])[CH3:46])[CH:20]([CH3:21])[CH3:22])=[O:26])[CH2:28][CH2:29]3)=[CH:38][CH:37]=2)[CH:19]=[CH:18][CH:17]=1)[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:8])#[N:12]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 222357482-(3-bromophenoxy)-N-(cyanomethyl)-4-methylpentanamideHCID 222360254-(4-{[(Triisopropylsilyl)oxy]carbonyl}-1-piperazinyl)phenylboronic acid

Product 1

HCID 10282346Triisopropylsilyl 4-[3'-(1-{[(cyanomethyl)amino]carbonyl}-3-methylbutoxy)[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 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To 2-(3-bromophenoxy)-N-(cyanomethyl)-4-methylpentanamide (1 g, 3.07 mmoles) in toluene (20 mL) was added 4-(4-{[(triisopropylsilyl)oxy]carbonyl}-1-piperazinyl)phenylboronic acid (1.25g, 3.07 mmoles) followed by solid potassium carbonate (0.85 g, 6.14 mmoles) and finally [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (250 mg, 0.31 mmoles). The reaction was stirred overnight at 80° 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 triisopropylsilyl 4-[3′-(1-{[(cyanomethyl)amino]carbonyl}-3-methylbutoxy)[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-b89418703944482e83a19f87ffa28e84
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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