Sodium Hydroxide → 4-(5-Amino-isoquinoline-6-yloxy)-piperidin-1-carboxylic acid tert-butyl ester

HRID 1887072Notes

Reaction equation

[OH-].[Na+].[NH:3]1CCC[C@H]1C(O)=O.[N-]=[N+]=[N-].[Na+].[C:15]([O:19][C:20]([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:21])([CH3:18])([CH3:17])[CH3:16]>O.[Cu]I.C(OCC)(=O)C>[C:15]([O:19][C:20]([N: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)=[O:21])([CH3:18])([CH3:17])[CH3:16]

Participants

Conditions

Temperature: 95 °C

Procedure

Under argon atmosphere 600 μL (0.6 mmol) of 1 N NaOH, 13.8 mg (0.12 mmol) L-proline, 7.6 mg (0.04 mmol) of CuI and 52 mg (0.8 mmol) of NaN3 were added to a solution of 163 mg (0.4 mmol) 4-(5-bromo-isoquinoline-6-yloxy)-piperidin-1-carboxylic acid tert-butyl ester (11) in 0.6 mL of water. The mixture was heated to 95° C. for 3 h in a microwave reactor (CEM Discovery). After cooling to room temperature water and ethyl acetate were added. The mixture was filtered through Celite, washed with ethyl acetate and concentrated. The crude product was purified by preparative HPLC to yield 42 mg of compound 18 (containing some 11 as impurity).

Workup

additionwere added
filtrationThe mixture was filtered through Celite
washwashed with ethyl acetate
concentrationconcentrated
customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record: ord-c2dadb485bdc4d3bbe5f614bb5c41563
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08501736B2

Reaction notes

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