Diisopropylethylamine → HCID 50908286, compound

HRID 2088474Notes

Reaction equation

HRID 2088474 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:13]([C:14]([OH:16])=O)=[CH:12][N:11]([CH2:17][CH2:18][OH:19])[C:10](=[O:20])[NH:9]2)=[CH:4][CH:3]=1.[CH3:21][O:22][C:23]1[C:28]([O:29][CH3:30])=[CH:27][C:26]([NH2:31])=[C:25]([CH3:32])[CH:24]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH3:21][O:22][C:23]1[C:28]([O:29][CH3:30])=[CH:27][C:26]([NH:31][C:14]([C:13]2[CH:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[NH:9][C:10](=[O:20])[N:11]([CH2:17][CH2:18][OH:19])[CH:12]=2)=[O:16])=[C:25]([CH3:32])[CH:24]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2665854,5-Dimethoxy-2-methylanilineHCID 2724699PyBOPHCID 58128622HCID 58128622, compound

Product 1

HCID 50908286HCID 50908286, compoundYield 23.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(4-Fluoro-phenyl)-1-(2-hydroxy-ethyl)-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid(180 mg), 4,5-dimethoxy-2-methyl-phenylamine (86 mg) and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP, 265 mg) were dissolved in 10 mL DMF, followed by 0.2 mL di-iso-propylethyl amine. The mixture was heated at 50° for 72 hours, then cooled, diluted with aqueous pH 2 buffer and ethyl acetate, and the layers separated. The organic layer was washed with saturated sodium bicarbonate and brine, then dried over Na2SO4, filtered and the solvent removed in vacuo. The residue was chromatographed in 3% MeOH/DCM. The fraction containing the product was washed with 10% aqueous HCl, and concentrated in vacuo to yield 52 mg of 4-(4-fluoro-phenyl)-1-(2-hydroxy-ethyl)-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid(4,5-dimethoxy-2-methyl-phenyl)-amide, MS (M+H)=430.

Workup

  1. temperatureThe mixture was heated at 50° for 72 hours
  2. temperaturecooled
  3. additiondiluted with aqueous pH 2 buffer
  4. customethyl acetate, and the layers separated
  5. washThe organic layer was washed with saturated sodium bicarbonate and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. customThe residue was chromatographed in 3% MeOH/DCM
  10. additionThe fraction containing the product
  11. washwas washed with 10% aqueous HCl
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cc677d51466342359ee19b2be44f07d7
Source dataset
uspto-grants-2013_05
Patent number
US08435990B2

Reaction notes

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