Hydrochloric Acid → HCID 89812805, compound

HRID 1481153Notes

Reaction equation

HRID 1481153 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10](Br)[CH:9]=2)=[O:4].C([Sn](CCCC)(CCCC)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)CCC.CCOC(C)=O.Cl>CN(C=O)C.[Cl-].[Na+].O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH:9]=2)=[O:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 607632TributylphenyltinHCID 89813103Methyl 7-bromo-4-hydroxyisoquinoline-3-carboxylate

Product 1

HCID 89812805HCID 89812805, compoundYield 75.6%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 7-bromo-4-hydroxy-isoquinoline-3-carboxylic acid methyl ester (400 mg, 1.42 mmol), tributylphenyltin (0.6 mL, 1.70 mmol), and PdCl2(PPh3)2 (200 mg, 0.28 mmol) in DMF (14 mL) was heated at 120° C. for 2 h under N2 atmosphere. After cooling the mixture to r.t., brine (10 mL) and EtOAc (30 mL) were added. 1 M HCl was added with stirring until pH was ˜3. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, washed with water, and dried over MgSO4. After evaporating the solvent, the crude product was purified by column chromatography (0-40% EtOAc/hexanes) to give 300 mg of the title compound. 1H NMR (CDCl3, 200 MHz): δ ppm=11.7 (s, 1H), 8.87 (s, 1H), 8.46 (d, 1H, J=8.6 Hz), 8.15 (d, 1H, J=1.4 Hz), 8.04 (dd, 1H, J=8.6 Hz, 2.0 Hz), 7.65-7.80 (m, 2H), 7.40-7.60 (m, 3H), 4.12 (s, 3H).

Workup

  1. temperatureAfter cooling the mixture to r.t.
  2. extractionThe aqueous layer was extracted with additional EtOAc
  3. washwashed with water
  4. dry with materialdried over MgSO4
  5. customAfter evaporating the solvent
  6. customthe crude product was purified by column chromatography (0-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-108816d123b24f489d36597439284049
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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