Triphenylphosphine → 3-(1-Amino-7-methylisoquinolin-6-yloxy)piperidine-1-carboxylic acid tert-butyl ester

HRID 1435983Notes

Reaction equation

HRID 1435983 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([OH:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:34][C:35]1[C:44]2[C:39](=[CH:40][C:41](O)=[C:42]([CH3:45])[CH:43]=2)[CH:38]=[CH:37][N:36]=1.CCOC(/N=N/C(OCC)=O)=O>CN(C=O)C.CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([O:14][C:41]2[CH:40]=[C:39]3[C:44](=[CH:43][C:42]=2[CH3:45])[C:35]([NH2:34])=[N:36][CH:37]=[CH:38]3)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 5456991-Boc-3-hydroxypiperidineHCID 5462977Diethyl azodicarboxylateHCID 1356269091-Amino-7-methylisoquinolin-6-ol

Product 1

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

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

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. washwashed with methanol
  2. washeluted with 2M ammonia in methanol
  3. customThe crude product was isolated
  4. customfurther purified

Sources & evidence

ORD record
ord-0372ae90a0f84d75914fc420beafd4aa
Source dataset
uspto-grants-2009_11
Patent number
US07618985B2

Reaction notes

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