HCID 68874923, compound → HCID 68874874, compound

HRID 1435986Notes

Reaction equation

HRID 1435986 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([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)[CH2:10][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:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1

Participants

4

Reactant 1

HCID 68874923HCID 68874923, compound

Product 1

HCID 68874874HCID 68874874, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A suspension of 1-amino-7-methylisoquinolin4-ol (430 mg, 2.4 mmol), 4-methanesulfonyloxypiperidine-1-carboxylic acid tert-butyl ester (1.0 g) and K2CO3 (510 mg, 3.7 mmol) in anhydrous N, N-dimethylformamide (8 ml) were microwaved at 100° C. for 10 minutes. A further equivalent of 4-methanesulfonyloxypiperidine-1-carboxylic acid tert-butyl ester in N, N-dimethylformamide (4 ml) was added and the mixture microwaved at 100° C. for a further 10 minutes. The mixture was diluted with water, acidified with acetic acid and further diluted with methanol. The mixture 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 flash chromatography on silica (eluent: 9:1:0.1 dichloromethane : methanol :ammonium hydroxide) to afford 4-(1-amino-7-methylisoquinolin-6-yloxy)piperidine-1-carboxylic acid tert-butyl ester (327 mg). A mixture of the 4-(1-amino-7-methylisoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester in dichloromethane (5 ml) and trifluoroacetic acid (2 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 to give 7-methyl-6-(piperidin-4-yloxy)isoquinolin-1-ylamine (270 mg), El-MS: m/z=258.4 [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

Sources & evidence

ORD record
ord-d49115807b5c402c89a6e73171c7fc8f
Source dataset
uspto-grants-2009_11
Patent number
US07618985B2

Reaction notes

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