Bromobenzene → HCID 86729370, compound

HRID 521208Notes

Reaction equation

HRID 521208 reaction equation
[NH2:1][C:2]1[C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][N:4]([C:11]2([CH2:24][C:25]#[N:26])[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[N:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[C:25]([CH2:24][C:11]1([N:4]2[CH:5]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[C:2]([NH:1][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[N:3]2)[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:15][CH2:16]1)#[N:26]

Participants

8

Reactant 4

HCID 7961BromobenzeneHCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86729369HCID 86729369, compound

Product 1

HCID 86729370HCID 86729370, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

To a microwave vessel was added tert-butyl 4-[3-amino-4-(methoxycarbonyl)-1H-pyrazol-1-yl]-4-(cyanomethyl)piperidine-1-carboxylate (0.400 g, 1.10 mmol), K3PO4 (467 mg, 2.20 mmol), bromobenzene (0.13 mL, 1.2 mmol), and dioxane (5.5 mL). The mixture was degassed by bubbling argon for 5 minutes. Pd2(dba)3 (50 mg, 0.05 mmol) and X-Phos (79 mg, 0.16 mmol) were added, and the vial was sealed and heated to 95° C. for 3 hours. The reaction was then cooled to ambient temperature, diluted with EtOAc, filtered through celite, and rinsed with EtOAc. The filtrate was concentrated in vacuo, and the residue was purified by MPLC on silica gel (using a gradient elution of 0-50% EtOAc/hexanes) to afford the title compound.

Workup

  1. customThe mixture was degassed
  2. customby bubbling argon for 5 minutes
  3. customthe vial was sealed
  4. temperatureThe reaction was then cooled to ambient temperature
  5. filtrationfiltered through celite
  6. washrinsed with EtOAc
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by MPLC on silica gel (
  9. washa gradient elution of 0-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d0b4fc414d5e41c8b8dd100bbcedc1f7
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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