Phenylurea → 4-Hydroxy-7-(3-phenyl-ureido)-isoquinoline-3-carboxylic acid ethyl ester

HRID 1481126Notes

Reaction equation

HRID 1481126 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11](Br)[CH:10]=2)=[O:5])[CH3:2].[C:18]1([NH:24][C:25]([NH2:27])=[O:26])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([NH:27][C:25]([NH:24][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:26])[CH:10]=2)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 6145PhenylureaHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 89813095Ethyl 7-bromo-4-hydroxyisoquinoline-3-carboxylate

Product 1

HCID 898131284-Hydroxy-7-(3-phenyl-ureido)-isoquinoline-3-carboxylic acid ethyl esterYield 84%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

7-Bromo-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester (250 mg, 0.8443 mmol) was combined in an oven-dried flask with phenyl urea (138 mg, 1.013 mmol), cesium carbonate (550 mg, 1.69 mmol), XantPhos (49 mg, 0.0844 mmol) and tris(dibenzylideneacetone)dipalladium(0) (25 mg, 0.0422 mmol). The flask was flushed with dry nitrogen and charged with dioxane (5 mL) and the solution brought to reflux. After 44 h, the reaction was cooled and the solution partitioned between equal volumes of ethyl acetate and brine resulting in precipitation. Filtration of the solid followed by vacuum drying provided the desired urea product in 84% yield. MS ESI(+) m/e: 352.0330 (M+1).

Workup

  1. customThe flask was flushed with dry nitrogen
  2. additioncharged with dioxane (5 mL)
  3. temperatureto reflux
  4. temperaturethe reaction was cooled
  5. customthe solution partitioned between equal volumes of ethyl acetate and brine resulting in precipitation
  6. filtrationFiltration of the solid
  7. customdrying

Sources & evidence

ORD record
ord-0eae81e3779b4a5a8f7b4fd44eee4c96
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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