Iodine → 8-cyclopentyl-6-iodo-5-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one

HRID 272454Notes

Reaction equation

HRID 272454 reaction equation
[CH:1]1([N:6]2[C:11]3[N:12]=[C:13]([S:16][CH3:17])[N:14]=[CH:15][C:10]=3[C:9]([CH3:18])=[CH:8][C:7]2=[O:19])[CH2:5][CH2:4][CH2:3][CH2:2]1.II.FC(F)(F)C(OC1C(OC(=O)C(F)(F)F)=C([I:33])C=CC=1)=O.S([O-])([O-])(=O)=S.[Na+].[Na+]>ClCCl>[CH:1]1([N:6]2[C:11]3[N:12]=[C:13]([S:16][CH3:17])[N:14]=[CH:15][C:10]=3[C:9]([CH3:18])=[C:8]([I:33])[C:7]2=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 807IodineHCID 24477Sodium ThiosulfateHCID 112658248-Cyclopentyl-5-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-oneHCID 12041285Bistrifluoroacetoxyiodobenzene

Product 1

HCID 113954978-cyclopentyl-6-iodo-5-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-oneYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The sulfide, 8-cyclopentyl-5-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one (7.03 g, 25.51 mmol) and iodine (7.12 g, 28.06 mmol) were combined in dry dichloromethane (120 mL). The mixture was shielded from light and stirred at room temperature for 27 minutes. Bis(trifluoroacetoxy)iodobenzene (13.16 g, 30.61 mmol) was added in one portion and the reaction mixture was heated to 37° C. for 2 h, then cooled to room temperature for 2 h. 50% Aqueous (w/v) sodium thiosulfate (114 mL) was added and the two phases were stirred for 30 minutes then separated. The aqueous phase was extracted with dichloromethane (50 mL) and the combined organic phases were washed with 50% aqueous (w/v) sodium thiosulfate (50 mL) and water (4×130 mL). The organic phase was dried, filtered and concentrated in vacuo to give crude product which was purified by chromatography (15% heptane/dichloromethane) to give 8-cyclopentyl-6-iodo-5-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one (5.94 g, 58%) as a white solid. MS (ESI); M++1: Calc'd, 401. Found 401. 1H NMR δ (300 MHz, CDCl3) 8.91 (s, 1H), 6.12-6.00 (m, 1H), 2.70 (s, 3H), 2.62 (s, 3H), 2.30-2.24 (m, 2H), 2.15-2.08 (m, 2H), 1.93-1.81 (m, 2H), 1.75-1.57 (m, 2H)

Workup

  1. temperaturethe reaction mixture was heated to 37° C. for 2 h
  2. temperaturecooled to room temperature for 2 h
  3. stirringthe two phases were stirred for 30 minutes
  4. customthen separated
  5. extractionThe aqueous phase was extracted with dichloromethane (50 mL)
  6. washthe combined organic phases were washed with 50% aqueous (w/v) sodium thiosulfate (50 mL) and water (4×130 mL)
  7. customThe organic phase was dried
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give crude product which
  11. customwas purified by chromatography (15% heptane/dichloromethane)

Sources & evidence

ORD record
ord-333d37fbd0694312b9b1d84b8e3a0a4e
Source dataset
uspto-grants-2008_11
Patent number
US07456168B2

Reaction notes

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