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

HRID 1271971Notes

Reaction equation

HRID 1271971 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-da2ff3bd5bf54d34a64c78b2faf389c7
Source dataset
uspto-grants-2007_04
Patent number
US07208489B2

Reaction notes

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