Potassium Carbonate → Ethyl 1-(4-methoxybenzylamino)isoquinoline-7-carboxylate

HRID 880967Notes

Reaction equation

HRID 880967 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH3:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH2:24])=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C.O>[CH3:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH:24][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:10]=3)[CH:5]=[CH:4][N:3]=2)=[CH:21][CH:20]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 754524-MethoxybenzylamineHCID 86664617Ethyl 1-chloroisoquinoline-7-carboxylate

Product 1

HCID 67491573Ethyl 1-(4-methoxybenzylamino)isoquinoline-7-carboxylateYield 55.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of ethyl 1-chloroisoquinoline-7-carboxylate (548 mg, 2.32 mmol) in N,N-dimethylformamide (9.3 mL) was added 4-methoxy-benzylamine (4.6 mL, 35 mmol) and potassium carbonate (5.14 g, 37.2 mmol). The reaction was heated to 70° C. and stirred overnight. The reaction was cooled to room temperature and was diluted with ethyl acetate and water. The layers were separated and the aqueous was extracted twice with ethyl acetate. The combined organics were washed with water and brine, dried over magnesium sulfate, filtered, and concentrated. Purification by flash column chromatography (0-35% ethyl acetate/heptanes) gave the title compound (430 mg, 55%) as a greenish oil. 1H NMR (400 MHz, CDCl3, δ): 8.49 (s, 1H), 8.16 (dd, J=8.6, 1.6 Hz, 1H), 8.09 (d, J=5.9 Hz, 1H), 7.69 (d, J=8.6 Hz, 1H), 7.33-7.40 (m, 2H), 6.96 (d, J=5.9 Hz, 1H), 6.87-6.93 (m, 2H), 5.67 (br. s., 1H), 4.76 (d, J=5.1 Hz, 2H), 4.41 (q, J =7.2 Hz, 2H), 3.81 (s, 3H), 1.37-1.43 (m, 3H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous was extracted twice with ethyl acetate
  4. washThe combined organics were washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash column chromatography (0-35% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-03542a47a4eb42f7b0d88d242c4c0c15
Source dataset
uspto-grants-2015_03
Patent number
US08993586B2

Reaction notes

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