2-Methyltetrahydrofuran → US9000184, 7, isomer 1

HRID 1468240Notes

Reaction equation

HRID 1468240 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.[Cl:25][C:26]1[CH:27]=[N:28][CH:29]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:31]=1.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>[Cl:25][C:26]1[CH:31]=[C:30]([C:2]2[CH:24]=[C:23]3[C:5]([CH2:6][CH2:7][C:8]4([C:16]53[N:20]=[C:19]([NH2:21])[C:18]([CH3:22])=[N:17]5)[CH2:9][CH2:10][CH:11]([O:14][CH3:15])[CH2:12][CH2:13]4)=[CH:4][CH:3]=2)[CH:29]=[N:28][CH:27]=1

Participants

9

Reactant 5

HCID 73012-MethyltetrahydrofuranHCID 11430Potassium CarbonateHCID 231578663-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 249491873-(Di-tert-butylphosphonium)propane sulfonateHCID 72714746US9000184, 5, isomer 1

Product 1

HCID 72714841US9000184, 7, 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, 0.2 g, 0.51 mmol), 3-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (123 mg, 0.51 mmol), 3-(di-tert-butylphosphonium)propane sulfonate (0.014 g, 0.05 mmol), sodium tetrachloropalladate(II) (7.54 mg, 0.03 mmol), 2-methyltetrahydrofuran (3 mL) and aq. potassium carbonate (2.0 M, 0.769 mL, 1.54 mmol) were added to microwave vial. The vial was sealed and heated in the 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. This procedure was repeated twice more. Water and 2-Me THF were added. The water phase was eliminated and the organic phase was washed once with brine and water. The organic phase was concentrated in vacuo. The product was purified using prep HPLC 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 water
  4. concentrationThe organic phase was concentrated in vacuo
  5. customThe product was purified
  6. customto give

Sources & evidence

ORD record
ord-48a7d74197bc4ce8bf9f7ba343716eec
Source dataset
uspto-grants-2015_04
Patent number
US09000184B2

Reaction notes

Loading…