Sodium Carbonate → 3-[2(R)-{ethoxycarbonylpropyl-amino}-2-phenylethyl]-5-(2-chloro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-2,4(1H,3H)-dione

HRID 347787Notes

Reaction equation

HRID 347787 reaction equation
[NH2:1][C@H:2]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:3][N:4]1[C:9](=[O:10])[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[C:12]=2[Cl:19])=[CH:7][N:6]([CH2:20][C:21]2[C:26]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:24]=[CH:23][C:22]=2[F:31])[C:5]1=[O:32].C([O-])([O-])=O.[Na+].[Na+].Br[CH2:46][CH2:47][CH2:48][C:49]([O:51][CH2:52][CH3:53])=[O:50]>CN(C=O)C>[CH2:52]([O:51][C:49]([CH2:48][CH2:47][CH2:46][NH:1][C@H:2]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:3][N:4]1[C:9](=[O:10])[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[C:12]=2[Cl:19])=[CH:7][N:6]([CH2:20][C:21]2[C:26]([C:27]([F:28])([F:30])[F:29])=[CH:25][CH:24]=[CH:23][C:22]=2[F:31])[C:5]1=[O:32])=[O:50])[CH3:53]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 76300Ethyl 4-bromobutyrateHCID 11376252(R)-1-(2-fluoro-6-(trifluoromethyl)benzyl)-3-(2-amino-2-phenylethyl)-5-(2-chloro-3-methoxyphenyl)pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 865965103-[2(R)-{ethoxycarbonylpropyl-amino}-2-phenylethyl]-5-(2-chloro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-2,4(1H,3H)-dioneYield 53.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of compound 7h (2.0 g, 3.65 mmol) in DMF (8 mL) was added Na2CO3 (0.47 g, 4.38 mmol) followed by ethyl 4-bromobutyrate (0.83 mL, 5.48 mmol). The mixture was heated at 95° C. for 1.5 hours, cooled to room temperature, and partitioned between ethyl acetate and H2O. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel with ethyl acetate/hexanes/triethylamine 500/500/5 to afford compound 7i (1.29 g) as a white solid. MS (CI) m/z 662.2, 664.2 (MH+)

Workup

  1. temperaturecooled to room temperature
  2. custompartitioned between ethyl acetate and H2O
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel with ethyl acetate/hexanes/triethylamine 500/500/5

Sources & evidence

ORD record
ord-a6646119375548df86972d77fd474cb2
Source dataset
uspto-grants-2007_02
Patent number
US07176211B2

Reaction notes

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