Sodium Hydroxide → 6-(Piperidin-4-yloxy)-isoquinolin-5-ylamine

HRID 1887081Notes

Reaction equation

HRID 1887081 reaction equation
[OH-].[Na+].[NH:3]1CCC[C@H]1C(O)=O.[N-]=[N+]=[N-].[Na+].C(OC([N:22]1[CH2:27][CH2:26][CH:25]([O:28][C:29]2[C:30](Br)=[C:31]3[C:36](=[CH:37][CH:38]=2)[CH:35]=[N:34][CH:33]=[CH:32]3)[CH2:24][CH2:23]1)=O)(C)(C)C>C(O)C.O.[Cu]I.C(OCC)(=O)C.O>[NH:22]1[CH2:27][CH2:26][CH:25]([O:28][C:29]2[C:30]([NH2:3])=[C:31]3[C:36](=[CH:37][CH:38]=2)[CH:35]=[N:34][CH:33]=[CH:32]3)[CH2:24][CH2:23]1

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 33557Sodium AzideHCID 145742L-ProlineHCID 576469744-(5-Bromo-isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 576469576-(Piperidin-4-yloxy)-isoquinolin-5-ylamineYield 123.4%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 19096565Water ethanolSolvent

Conditions

Temperature
95 °C

Procedure

60 μL of 1 N NaOH-solution, 6.9 mg (0.3 eq) of L-proline, 3.8 mg (0.1 eq) of CuI and 26 mg (0.4 mmol) of NaN3 were added to a solution of 82 mg (0.2 mmol) of 4-(5-Bromo-isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (11) in 2 mL of ethanol/water (7/3). The mixture was heated to 95° C. for 3 h in a microwave reactor (CEM Discover). After cooling water and ethyl acetate were added and the mixture was filtered through a celite cartridge. After removal of the solvents by distillation the remainder was subjected to preparative HPLC. The N-Boc-protected intermediate was deprotected by treatment with 2 mL 5-6 N HCl in isopropanol for 2 h at room temperature. Then water was added and all solvents were removed by freeze drying to yield 18 mg of compound 31 as hydrochloride.

Workup

  1. additionwere added
  2. filtrationthe mixture was filtered through a celite cartridge
  3. customAfter removal of the solvents
  4. distillationby distillation the remainder
  5. additionThen water was added
  6. customall solvents were removed by freeze
  7. customdrying

Sources & evidence

ORD record
ord-c1b63cf830554d0585a2dda9bd6cc5e6
Source dataset
uspto-grants-2013_08
Patent number
US08501736B2

Reaction notes

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