Phenylboronic Acid → HCID 57442337, compound

HRID 2262715Notes

Reaction equation

HRID 2262715 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]([N:17]3[CH2:22][CH2:21][N:20]([CH:23]4[CH2:26][CH2:25][CH2:24]4)[CH2:19][CH2:18]3)=[O:16])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[C:27]1(B(O)O)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>O1CCOCC1.C([O-])([O-])=O.[K+].[K+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:2]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:7]=[CH:6][CH:5]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]([N:17]3[CH2:22][CH2:21][N:20]([CH:23]4[CH2:26][CH2:25][CH2:24]4)[CH2:19][CH2:18]3)=[O:16])[CH2:10][CH2:9]2)[CH:3]=1

Participants

6

Reactant 2

HCID 66827Phenylboronic AcidHCID 57442338HCID 57442338, compound

Product 1

HCID 57442337HCID 57442337, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 11430Potassium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

In a sealed vial, dissolve 1-(3-bromophenyl)-4-[2-(4-cyclobutylpiperazin-1-yl)-2-oxoethyl]piperazine (17 mg, 0.04 mmol), phenyl boronic acid (9.8 mg, 0.08 mmol), and Pd(PPh3)4 (2.3 mg, 0.002 mmol) in dioxane (0.7 mL) and 2N K2CO3 (0.1 mL). Degas with N2 and seal the vial. Heat the mixture at 85° C. overnight. Cool and add partition EtOAc (0.5 mL) and 1N NaOH (0.5 mL). Extract the organic phase and place directly on SCX ion exchange resin. Wash the resin with EtOAc/MeOH (9:1). Discard this wash. Wash the resin with EtOAc/MeOH/TEA(9:1:1) and collect. Remove the solvent to yield the title compound. 1H NMR (CDCl3) δ 7.59-7.56 (m, 2H) 7.45-7.40 (m, 2H), 7.36-7.31 (m, 2H), 7.13-7.07 (m, 2H) 6.94-6.90 (m, 1H), 3.64 (t, 4H), 3.29-3.25 (m, 6H), 2.73-2.67 (m, 5H), 2.33-2.27 (m, 4H), 2.06-2.02 (m, 2H), 1.90-1.83 (m, 2H), 1.75-1.69 (m, 2H); LC-MS (M+1) 419.06.

Workup

  1. customDegas with N2
  2. customseal the vial
  3. temperatureCool
  4. additionadd
  5. custompartition EtOAc (0.5 mL) and 1N NaOH (0.5 mL)
  6. extractionExtract the organic phase and place directly on SCX ion exchange resin
  7. washWash the resin with EtOAc/MeOH (9:1)
  8. washWash the resin with EtOAc/MeOH/TEA(9:1:1)
  9. customcollect
  10. customRemove the solvent

Sources & evidence

ORD record
ord-e4df53cf2d0d458ca89c1cf461d192ff
Source dataset
uspto-grants-2010_12
Patent number
US07851474B2

Reaction notes

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