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

HRID 1243230Notes

Reaction equation

HRID 1243230 reaction equation
C([Si](C)(C)[O:6][C@H:7]1[CH2:11][CH2:10][C@H:9]([N:12]2[C:17]3=[N:18][C:19]([NH:22][C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)=[N:20][CH:21]=[C:16]3[CH2:15][N:14]([C:30]3[CH:35]=[CH:34][C:33]([CH2:36][CH3:37])=[CH:32][CH:31]=3)[C:13]2=[O:38])[CH2:8]1)(C)(C)C.N1C=CC=CC=1.F>N1C=CC=CC=1>[CH2:36]([C:33]1[CH:34]=[CH:35][C:30]([N:14]2[CH2:15][C:16]3[C:17](=[N:18][C:19]([NH:22][C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)=[N:20][CH:21]=3)[N:12]([C@H:9]3[CH2:10][CH2:11][C@H:7]([OH:6])[CH2:8]3)[C:13]2=[O:38])=[CH:31][CH:32]=1)[CH3:37]

Participants

4

Reactant 2

HCID 64774Pyridine, hydrofluoride (1:1)HCID 69584210(+/-)-1-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Product 1

HCID 69582145(+/-)-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-1-(trans-3-hydroxy-cyclopentyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of (±)-1-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (47 mg, 0.08 mmol) in pyridine (1 mL) (Fisher) was treated at room temperature with hydrogen fluoride-pyridine (0.6 mL) (Aldrich) for 20 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 (±)-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-1-(trans-3-hydroxy-cyclopentyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as a white solid. (Yield 32 mg, 87%).

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-8a2ca0131da049f3a9c5362d066d6f68
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

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