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

HRID 1022861Notes

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 1N 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-521ba40ea0b04945bfd6fc153fb49c55
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08722671B2

Reaction notes

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