Pyridine, hydrofluoride (1:1) → (R)-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-1-(2-hydroxy-1-methyl-ethyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

HRID 1243226Notes

Reaction equation

HRID 1243226 reaction equation
C([Si](C)(C)[O:6][CH2:7][C@H:8]([N:10]1[C:15]2=[N:16][C:17]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[N:18][CH:19]=[C:14]2[CH2:13][N:12]([C:28]2[CH:33]=[CH:32][C:31]([CH2:34][CH3:35])=[CH:30][CH:29]=2)[C:11]1=[O:36])[CH3:9])(C)(C)C.N1C=CC=CC=1.F>N1C=CC=CC=1>[CH2:34]([C:31]1[CH:32]=[CH:33][C:28]([N:12]2[CH2:13][C:14]3[C:15](=[N:16][C:17]([NH:20][C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)=[N:18][CH:19]=3)[N:10]([C@H:8]([CH3:9])[CH2:7][OH:6])[C:11]2=[O:36])=[CH:29][CH:30]=1)[CH3:35]

Participants

4

Reactant 2

HCID 64774Pyridine, hydrofluoride (1:1)HCID 11364631(R)-1-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Product 1

HCID 11362184(R)-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-1-(2-hydroxy-1-methyl-ethyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

(R)-1-[2-(tert-Butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (100 mg, 0.18 mmol) (from Example 38f supra) in pyridine (1.5 mL) (Fisher) was treated at room temperature with hydrogen fluoride-pyridine (0.6 mL) (Aldrich) for 15 minutes. The reaction mixture was quenched with 1 N aqueous hydrochloric acid at 0° C., then extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (50% ethyl acetate in hexanes) to give (R)-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-1-(2-hydroxy-1-methyl-ethyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as a colorless viscous oil. (Yield 45 mg, 61%).

Workup

  1. customThe reaction mixture was quenched with 1 N aqueous hydrochloric acid at 0° C.
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography (50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-99037ab23f4a436094b4af1af2e73bfd
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

Loading…