Glycol monoethyl ether → 8-cyclopentyl-6-(2-ethoxy-ethoxy)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one

HRID 586498Notes

Reaction equation

HRID 586498 reaction equation
[H-].[Na+].[CH2:3]([O:5][CH2:6][CH2:7][OH:8])[CH3:4].[CH:9]1([N:14]2[C:19]3[N:20]=[C:21]([S:24][CH3:25])[N:22]=[CH:23][C:18]=3[CH:17]=[C:16](F)[C:15]2=[O:27])[CH2:13][CH2:12][CH2:11][CH2:10]1>C1COCC1>[CH:9]1([N:14]2[C:19]3[N:20]=[C:21]([S:24][CH3:25])[N:22]=[CH:23][C:18]=3[CH:17]=[C:16]([O:8][CH2:7][CH2:6][O:5][CH2:3][CH3:4])[C:15]2=[O:27])[CH2:13][CH2:12][CH2:11][CH2:10]1

Participants

5

Reactant 3

HCID 8076Glycol monoethyl etherHCID 24758Sodium hydrideHCID 223298828-Cyclopentyl-6-fluoro-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one

Product 1

HCID 111871828-cyclopentyl-6-(2-ethoxy-ethoxy)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of sodium hydride (45 mg, 1.1 mmol, 60% oil dispersion) in THF (10 mL), under nitrogen, was added 2-ethoxyethanol (113 mg, 1.25 mmol). The reaction mixture was stirred at RT for 30 min. To this mixture, 8-cyclopentyl-6-fluoro-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one was added. The reaction mixture was then heated to reflux and stirred overnight. The cooled solution was quenched with water (25 mL) and extracted with ethyl acetate (50 mL). The organic layer was subsequently washed twice with aq. NH4Cl (20 mL each) and brine (20 mL). The organic layer was dried over magnesium sulfate. Removal of the drying agents and evaporation of the solvent gave a yellow oil, which was chromatographed on silica gel eluted with an ethyl acetate/hexane gradient to give 8-cyclopentyl-6-(2-ethoxy-ethoxy)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one as a clear oil (289 mg, 0.83 mmol). 1H NMR δ(400 MHz, CDCl3) 8.52 (s, 1H), 6.77 (s, 1H), 6.04-5.95 (m, 1H), 4.16 (t, J=4.0 Hz, 2H), 3.86 (t, J=4.0 Hz, 2H), 3.58 (q, J=8.0 Hz, 2H), 2.59 (s, 3H), 2.34-2.25 (m, 2H), 2.13-2.03 (m, 2H), 1.91-1.82 (m, 2H), 1.71-1.60 (m, 2H), 1.20 (t, J=8.0 Hz, 3H); MS (APCI+) 350 (M+1).

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureto reflux
  3. stirringstirred overnight
  4. customThe cooled solution was quenched with water (25 mL)
  5. extractionextracted with ethyl acetate (50 mL)
  6. washThe organic layer was subsequently washed twice with aq. NH4Cl (20 mL each) and brine (20 mL)
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. customRemoval of the drying agents and evaporation of the solvent
  9. customgave a yellow oil, which
  10. customwas chromatographed on silica gel
  11. washeluted with an ethyl acetate/hexane gradient

Sources & evidence

ORD record
ord-b6d49ceea85c4a70b96e4965ca3d220a
Source dataset
uspto-grants-2005_08
Patent number
US06936612B2

Reaction notes

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