Acetic Acid → HCID 68874923, compound

HRID 1435985Notes

Reaction equation

HRID 1435985 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[C:5](O)=[CH:4][N:3]=1.[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([O:27]S(C)(=O)=O)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C([O-])([O-])=O.[K+].[K+].C(O)(=O)C>CN(C)C=O.O.CO>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([O:27][C:8]2[CH:7]=[C:6]3[C:11](=[CH:10][C:9]=2[CH3:12])[C:2]([NH2:1])=[N:3][CH:4]=[CH:5]3)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine2×HCID 69017475HCID 69017475, compound

Product 1

HCID 68874923HCID 68874923, compoundYield 38.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

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. customwere microwaved at 100° C. for 10 minutes
  2. customthe mixture microwaved at 100° C. for a further 10 minutes
  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-83a63efb0dc94ef8a32f95a82ac36b7f
Source dataset
uspto-grants-2009_11
Patent number
US07618985B2

Reaction notes

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