Hydrochloric Acid → HCID 89812978, compound

HRID 1481134Notes

Reaction equation

HRID 1481134 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]#[C:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)CCC.O.Cl>CN(C=O)C.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.CCOC(C)=O>[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]#[C:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH:9]=2)=[O:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 630640Tributyl(2-phenylethynyl)stannaneHCID 89813103Methyl 7-bromo-4-hydroxyisoquinoline-3-carboxylate

Product 1

HCID 89812978HCID 89812978, compoundYield 104.3%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 7-bromo-4-hydroxy-isoquinoline-3-carboxylic acid methyl ester (500 mg, 1.77 mmol), tributyl(phenylethynyl)tin (0.8 mL, 2.13 mmol), and PdCl2(PPh3)2 (249 mg, 0.35 mmol) in DMF (18 mL) was heated at 120° C. for 2 h under N2 atmosphere. After cooling the mixture to r.t., water and EtOAc were added. 1 M HCl was added with stirring until pH was ˜2. 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 560 mg of the title compound as a yellow solid. MS: (+) m/z 304.10 (M+1).

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-56732a7944af4c9e92e2d625ecf15805
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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