Water → HCID 86610737, compound

HRID 1785354Notes

Reaction equation

HRID 1785354 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C@@H:8]([CH2:12][CH2:13][Br:14])[NH:7][CH2:6][CH2:5]2.[F:15][C:16]([F:21])([F:20])[C:17]([NH2:19])=[O:18].C(=O)([O-])[O-].[K+].[K+].[CH3:28][N:29]([CH3:33])[C:30](Cl)=[O:31].O>CN(C)C=O>[CH3:28][N:29]([CH3:33])[C:30]([O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C@@H:8]([CH2:12][CH2:13][Br:14])[NH:7][CH2:6][CH2:5]2)=[O:31].[F:15][C:16]([F:21])([F:20])[C:17]([NH2:19])=[O:18]

Participants

6

Reactant 4

HCID 962WaterHCID 6598Dimethylcarbamoyl ChlorideHCID 11430Potassium CarbonateHCID 86610735HCID 86610735, compound

Product 1

HCID 86610737HCID 86610737, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-hydroxy-1-(R)-(2-bromoethyl)-3,4-dihydro-1H-isoquinoline-trifluoroacetamide (270 mg, 0.77 mmol) obtained in step (d) of Example 190 and potassium carbonate (268 mg, 1.94 mmol) in dimethylformamide (3 ml) was added dimethylcarbamyl chloride (0.2 ml, 1.55 mmol) gradually with stirring under cooling in an ice bath. Subsequently, the resulting mixture was stirred at 40° C., and after confirming the disappearance of the starting material by thin layer chromatography, water was added to the reaction mixture, and the resulting mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of hexane and ethyl acetate (80:20) as the eluent to afford the title compound (170 mg, yield: 52%) as a colorless oil.

Workup

  1. temperatureunder cooling in an ice bath
  2. stirringSubsequently, the resulting mixture was stirred at 40° C.
  3. additionwas added to the reaction mixture
  4. extractionthe resulting mixture was extracted with ethyl acetate
  5. washThe extract was washed with saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated in vacuo
  8. customThe residue obtained
  9. customwas purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-d1e44508a28c4bb09872267ad0a0e331
Source dataset
uspto-grants-2009_03
Patent number
US07504437B2

Reaction notes

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