Dichloromethane → 7-(3-methyl-2-oxotetrahydropyrimidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

HRID 1162931Notes

Reaction equation

HRID 1162931 reaction equation
[C:1](Cl)(Cl)=[O:2].C(Cl)Cl.[CH3:8][NH:9][CH2:10][CH2:11][CH2:12][NH:13][C:14]1[CH:23]=[C:22]2[C:17]([CH:18]=[C:19]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:31]([F:34])([F:33])[F:32])[NH:20][C:21]2=[O:24])=[CH:16][CH:15]=1.C(N(CC)CC)C>O>[CH3:8][N:9]1[CH2:10][CH2:11][CH2:12][N:13]([C:14]2[CH:23]=[C:22]3[C:17]([CH:18]=[C:19]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[C:31]([F:33])([F:34])[F:32])[NH:20][C:21]3=[O:24])=[CH:16][CH:15]=2)[C:1]1=[O:2]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 6371PhosgeneHCID 8471TriethylamineHCID 575581337-(3-methylaminopropylamino)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

Product 1

HCID 575579037-(3-methyl-2-oxotetrahydropyrimidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-oneYield 14%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Phosgene (294 μl, 0.559 mmol) was added at 0° C. to an anhydrous methylene chloride solution (2 ml) that contained the 7-(3-methylaminopropylamino)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (70 mg, 0.186 mmol) obtained in step B. The obtained mixture was stirred for 10 minutes. Thereafter, triethylamine (156 μl, 0.112 mmol) was added to the reaction solution, and the obtained mixture was then stirred for 30 minutes. Thereafter, water was added to the reaction solution. An organic layer was separated, and a water layer was then extracted with methylene chloride. The organic layer was mixed with the extract. The obtained mixture was washed with water and a saturated saline solution, and was then dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure. The obtained residue was purified by amino silica gel column chromatography (methylene chloride:methanol=40:1), so as to obtain 7-(3-methyl-2-oxotetrahydropyrimidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (10.2 mg, 14%).

Workup

  1. stirringthe obtained mixture was then stirred for 30 minutes
  2. customAn organic layer was separated
  3. extractiona water layer was then extracted with methylene chloride
  4. additionThe organic layer was mixed with the extract
  5. washThe obtained mixture was washed with water
  6. dry with materiala saturated saline solution, and was then dried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled away under reduced pressure
  8. customThe obtained residue was purified by amino silica gel column chromatography (methylene chloride:methanol=40:1)

Sources & evidence

ORD record
ord-1ec3d0687496447fa0a81e3669038f02
Source dataset
uspto-grants-2010_10
Patent number
US07820693B2

Reaction notes

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