Potassium Carbonate → HCID 24957430, compound

HRID 1522834Notes

Reaction equation

HRID 1522834 reaction equation
[C:1]1([OH:12])[C:10]2[C:5](=[CH:6][C:7]([OH:11])=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.I[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1.N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[K+].[K+]>[Cu]I.O.CS(C)=O>[OH:11][C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[C:1](=[O:12])[N:2]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[CH:3]=[CH:4]2

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 696764-IodoanisoleHCID 145742L-ProlineHCID 178515735HCID 178515735, compound

Product 1

HCID 24957430HCID 24957430, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
130 °C

Procedure

6-Methoxyisoquinoline-1-ol was prepared as described above, followed by deprotection of the methoxy group using chlorobenzene and boron tribromide (6 equivalents, neat) added dropwise under argon atmosphere at room temperature, to obtain isoquinoline-1,6-diol (14v). Compound 14v (11.5 mmol) reacted with 4-iodoanisole (4.01 g, 17.13 mmol), copper (I) iodide (0.44 g, 2.28 mmol). L-proline (0.53 g, 4.57 mmol) and anhydrous potassium carbonate (3.16 g, 22.84 mmol) were placed in a dry 250 mL three-necked round-bottomed flask fitted with a stirring bar and reflux condenser. The reaction flask was vacuumed and refilled with dry argon. 50 mL of anhydrous methyl sulfoxide was added via syringe. The reaction mixture was stirred and heated to 130° C. for 20 hours. 50 mL of water was added to quench the reaction, and solid precipitated out. The solid was filtered, washed with water (2×20 mL) and dried in air. This solid was purified by flash column chromatography (silica gel, ethyl acetate) to give 6-hydroxy-2-(4-methoxyphenyl)isoquinolin-1(2H)-one (14w) a brown solid product. Compound 14w (1.8 mmol) was placed in a dry 250 mL single-necked round-bottomed flask fitted with a stirring bar and septa. Acetonitrile (10 mL) was added via a syringe under argon atmosphere at room temperature. N-Bromosuccinimide or NBS (0.33 g, 1.87 mmol) was added portionwise under argon atmosphere at room temperature. The reaction mixture was allowed to stir at room temperature for 2 hours. 20 mL of saturated sodium bicarbonate solution was then added. The mixture was extracted with ethyl acetate (3×10 mL). Organic layers were separated, dried over anhydrous magnesium sulfate and concentrated under vacuum. The residue was purified by flash column chromatography (silica gel, hexanes/EtOAc=2/3 v/v) to give white solid of 4-bromo-6-hydroxy-2-(4-methoxyphenyl)isoquinolin-1(2H)-one (14xME)

Workup

  1. customfitted with a stirring bar
  2. temperaturereflux condenser
  3. additionrefilled with dry argon
  4. customto quench
  5. customthe reaction, and solid
  6. customprecipitated out
  7. filtrationThe solid was filtered
  8. washwashed with water (2×20 mL)
  9. customdried in air
  10. customThis solid was purified by flash column chromatography (silica gel, ethyl acetate)

Sources & evidence

ORD record
ord-1f3197f81dab4d9b933d143e1e4567ba
Source dataset
uspto-grants-2015_07
Patent number
US09078888B2

Reaction notes

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