3-(1-Amino-7-methylisoquinolin-6-yloxy)piperidine-1-carboxylic acid tert-butyl ester → 7-Methyl-6-(piperidin-3-yloxy)isoquinolin-1-ylamine

HRID 1435984Notes

Reaction equation

HRID 1435984 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([O:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][C:24]=2[CH3:25])[C:21]([NH2:26])=[N:20][CH:19]=[CH:18]3)[CH2:9]1)=O)(C)(C)C>ClCCl.FC(F)(F)C(O)=O>[CH3:25][C:24]1[CH:23]=[C:22]2[C:17]([CH:18]=[CH:19][N:20]=[C:21]2[NH2:26])=[CH:16][C:15]=1[O:14][CH:10]1[CH2:11][CH2:12][CH2:13][NH:8][CH2:9]1

Participants

4

Reactant 1

HCID 688754323-(1-Amino-7-methylisoquinolin-6-yloxy)piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 688757327-Methyl-6-(piperidin-3-yloxy)isoquinolin-1-ylamine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 3-hydroxypiperidine-1-carboxylic acid tert-butyl ester (231 mg, 1.15 mmol), triphenylphosphine (301 mg, 1.15 mmol), 1-amino-7-methylisoquinolin-6-ol (200 mg, 1.15 mmol) in DMF (5 ml) at 0° C., under argon, was added dropwise diethylazodicarboxylate (181 [μL, 1.15 mmol). The mixture was then warmed to ambient temperature and stirred for 24 h. Methanol was added and the mixture loaded onto a pre-acidified SCX column, washed with methanol and then eluted with 2M ammonia in methanol. The crude product was isolated and further purified using prep-HPLC to give 3-(1-Amino-7-methylisoquinolin-6-yloxy)piperidine-1-carboxylic acid tert-butyl ester. A mixture of the (3-(1-Amino-7-methylisoquinolin-6-yloxy)piperidine-1-carboxylic acid tert-butyl ester in dichloromethane (10 ml) and trifluoroacetic acid (3 ml) was stirred at ambient temperature overnight. The mixture was concentrated in vacuo to give a residue. The residue was loaded onto a pre-acidified SCX column, washed with methanol and then eluted with 2M ammonia in methanol. The crude product was isolated and further purified using prep-HPLC to give 7-methyl-6-(piperidin-3-yloxy)isoquinolin-1-ylamine, El-MS: m/z=258.3 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customto give a residue
  3. washwashed with methanol
  4. washeluted with 2M ammonia in methanol
  5. customThe crude product was isolated
  6. customfurther purified

Sources & evidence

ORD record
ord-dc205e06e0b046df87f7967c7e3ab4ca
Source dataset
uspto-grants-2009_11
Patent number
US07618985B2

Reaction notes

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