Potassium Carbonate → Methyl 4-(benzyloxy)-7-(4-methoxybenzylamino)isoquinoline-3-carboxylate

HRID 1481144Notes

Reaction equation

HRID 1481144 reaction equation
[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15](Br)=[CH:16][CH:17]=2)[CH:12]=[N:11][C:10]=1[C:20]([O:22][CH3:23])=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24][O:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][NH2:31])=[CH:28][CH:27]=1.N1CCC[C@H]1C(O)=O.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.C(Cl)Cl.O.[Cu]I>[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([NH:31][CH2:30][C:29]3[CH:32]=[CH:33][C:26]([O:25][CH3:24])=[CH:27][CH:28]=3)=[CH:16][CH:17]=2)[CH:12]=[N:11][C:10]=1[C:20]([O:22][CH3:23])=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 754524-MethoxybenzylamineHCID 145742L-ProlineHCID 89812966Methyl 4-(benzyloxy)-7-bromoisoquinoline-3-carboxylate

Product 1

HCID 89812996Methyl 4-(benzyloxy)-7-(4-methoxybenzylamino)isoquinoline-3-carboxylate

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of methyl 4-(benzyloxy)-7-bromoisoquinoline-3-carboxylate (372.0 mg, 1.0 mmol), 4-methoxybenzylamine (0.2 mL, 1.5 mmol, TCI), CuI (19.0 mg, 0.1 mmol), proline (23.0 mg, 0.2 mmol) and K2CO3 (276.4 mg, 2.0 mmol) in DMSO (0.6 mL) was stirred at 80° C. for 24 hours under a nitrogen atmosphere. After cooling to room temperature, the mixture was diluted with CH2Cl2 (50 mL) and H2O (50 mL). The layers were separated and the aqueous layer was extracted twice with CH2Cl2. The combined organic layers were dried over MgSO4, concentrated, and purified by flash chromatography (0-30% EtOAc/CH2Cl2) to give the title compound in 137.0 mg. 1H NMR (CDCl3, 200 MHz): δ=8.82 (s, 1H), 7.96 (d, 1H, J=9.0 Hz), 7.54 (d, 2H, J=6.6 Hz), 7.42-7.27 (m, 5H), 7.05 (d, 1H, J=9.0 Hz), 6.93-6.87 (m, 3H), 5.18 (s, 2H), 4.38 (d, 2H, J=5.0 Hz), 4.00 (s, 3H), 3.82 (s, 3H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted twice with CH2Cl2
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated
  6. custompurified by flash chromatography (0-30% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-37ee1b77ee70472e80e0187f6dbaf32e
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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