Tetrabutylammonium Fluoride → HCID 86696683, compound

HRID 1774184Notes

Reaction equation

HRID 1774184 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][CH2:27][CH:28]([N:36]1[CH:41]=[CH:40][C:39]([C:42]2[C:47]([F:48])=[CH:46][N:45]=[C:44]([NH:49][CH:50]3[CH2:55][CH2:54][O:53][CH2:52][CH2:51]3)[N:43]=2)=[CH:38][C:37]1=[O:56])[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[CH:30]=1)(C(C)(C)C)(C)C>C1COCC1>[Cl:35][C:31]1[CH:30]=[C:29]([CH:28]([N:36]2[CH:41]=[CH:40][C:39]([C:42]3[C:47]([F:48])=[CH:46][N:45]=[C:44]([NH:49][CH:50]4[CH2:55][CH2:54][O:53][CH2:52][CH2:51]4)[N:43]=3)=[CH:38][C:37]2=[O:56])[CH2:27][OH:26])[CH:34]=[CH:33][CH:32]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86696682HCID 86696682, compound

Product 1

HCID 86696683HCID 86696683, compoundYield 52.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1M Tetrabutylammonium fluoride in THF (0.165 mL, 0.165 mmol) was added to 1-(2-(tert-butyldimethylsilyloxy)-1-(3-chlorophenyl)ethyl)-4-(5-fluoro-2-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-4-yl)pyridin-2(1H)-one (0.0307 g, 0.0549 mmol) in THF (3 mL). The mixture was stirred at room temperature for 30 minutes. The reaction mixture was evaporated, and the residue was partitioned between water and EtOAc. The EtOAc was washed with brine, dried over MgSO4, filtered, and evaporated to yield a crude product as a film. The crude product was purified by chromatography on a 10 g Biotage SNAP column with EtOAc. Fractions 17-32 contained a glass (16.2 mg). The glass was triturated with water and dried to afford 1-(1-(3-chlorophenyl)-2-hydroxyethyl)-4-(5-fluoro-2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (0.0129 g, 0.0290 mmol, 52.8% yield) as a film. 1H NMR (400 MHz, CD3OD) δ 8.33 (d, 1H), 7.84 (d, 1H), 7.43-7.24 (m, 5H), 7.03-6.99 (m, 1H), 6.16-6.12 (m, 1H), 4.32-4.27 (m, 1H), 4.22-4.17 (m, 1H), 4.02-3.94 (m, 3H), 3.57-3.49 (m, 2H), 2.02-1.96 (m, 2H), 1.64-1.54 (m, 2H); m/z (APCI-pos) M+1=445.1.

Workup

  1. customThe reaction mixture was evaporated
  2. customthe residue was partitioned between water and EtOAc
  3. washThe EtOAc was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto yield a crude product as a film
  8. customThe crude product was purified by chromatography on a 10 g Biotage SNAP column with EtOAc
  9. customThe glass was triturated with water
  10. customdried

Sources & evidence

ORD record
ord-6932501761b048ab9a3f0781b18bd75b
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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