2-Methyltetrahydrofuran → US9000184, 6, isomer 1

HRID 1468239Notes

Reaction equation

HRID 1468239 reaction equation
Br[C:2]1[CH:24]=[C:23]2[C:5]([CH2:6][CH2:7][C:8]3([C:16]42[N:20]=[C:19]([NH2:21])[C:18]([CH3:22])=[N:17]4)[CH2:13][CH2:12][CH:11]([O:14][CH3:15])[CH2:10][CH2:9]3)=[CH:4][CH:3]=1.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH:32]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:34]=1)[C:30]#[N:31].CC([PH+](C(C)(C)C)CCCS([O-])(=O)=O)(C)C.CC1CCCO1.C(=O)([O-])[O-].[K+].[K+]>[Na+].[Na+].Cl[Pd+2](Cl)(Cl)Cl.[Pd].O>[NH2:21][C:19]1[C:18]([CH3:22])=[N:17][C:16]2([C:23]3[C:5](=[CH:4][CH:3]=[C:2]([C:33]4[CH:32]=[C:29]([CH:28]=[C:27]([O:26][CH3:25])[CH:34]=4)[C:30]#[N:31])[CH:24]=3)[CH2:6][CH2:7][C:8]32[CH2:9][CH2:10][CH:11]([O:14][CH3:15])[CH2:12][CH2:13]3)[N:20]=1

Participants

9

Reactant 5

HCID 73012-MethyltetrahydrofuranHCID 11430Potassium CarbonateHCID 249491873-(Di-tert-butylphosphonium)propane sulfonateHCID 467393223-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 72714746US9000184, 5, isomer 1

Product 1

HCID 72714747US9000184, 6, isomer 1

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 178479786HCID 178479786, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
130 °C

Procedure

7′-Bromo-4-methoxy-5″-methyl-3′,4′-dihydrodispiro[cyclohexane-1,2′-naphthalene-1′,2″-imidazol]-4″-amine (Example 5, 0.184 g, 0.47 mmol), 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (0.122 g, 0.47 mmol), 3-(di-tert-butylphosphonium)propane sulfonate (0.013 g, 0.05 mmol), sodium tetrachloropalladate(II) (6.95 mg, 0.02 mmol), 2-methyltetrahydrofuran (3 mL) and potassium carbonate (2.0 M, 0.708 mL, 1.42 mmol) were added to a microwave vial. The vial was sealed and heated with MW for 30 min at 130° C. The same amount of ligand and Pd-catalyst were added again and the reaction was heated in the MW for 15 min at 130° C. Water and 2-Me THF was added and the water phase was eliminated. The organic phase was washed once with brine and once with water. The organic phase was concentrated in vacuo. The product was purified using prep HPLC. Fractions containing the isomeric products were collected separately and the MeOH was evaporated. DCM was added and the mixture was poured into a phase separator. The organic phase was concentrated in vacuo to give:

Workup

  1. customThe vial was sealed
  2. temperaturethe reaction was heated in the MW for 15 min at 130° C
  3. washThe organic phase was washed once with brine and once with water
  4. concentrationThe organic phase was concentrated in vacuo
  5. customThe product was purified
  6. additionFractions containing the isomeric products
  7. customwere collected separately
  8. customthe MeOH was evaporated
  9. additionDCM was added
  10. additionthe mixture was poured into a phase separator
  11. concentrationThe organic phase was concentrated in vacuo
  12. customto give

Sources & evidence

ORD record
ord-7dc2a86c95d54fa3ad825d9aeb760a3c
Source dataset
uspto-grants-2015_04
Patent number
US09000184B2

Reaction notes

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