Iodoethane → HCID 10387392, compound

HRID 1727020Notes

Reaction equation

HRID 1727020 reaction equation
Br[C:2]1[N:10]([CH2:11][C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:19])[C:9]2[C:8](=[O:20])[NH:7][C:6](=[O:21])[N:5]([CH3:22])[C:4]=2[N:3]=1.C([O-])([O-])=O.[K+].[K+].I[CH2:30][CH3:31].[NH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1>CN(C=O)C.O.CS(C)=O>[Cl:19][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]([F:18])[C:12]=1[CH2:11][N:10]1[C:9]2[C:8](=[O:20])[N:7]([CH2:30][CH3:31])[C:6](=[O:21])[N:5]([CH3:22])[C:4]=2[N:3]=[C:2]1[N:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

8

Reactant 4

HCID 6340IodoethaneHCID 8082PiperidineHCID 11430Potassium CarbonateHCID 980944HCID 980944, compound

Product 1

HCID 10387392HCID 10387392, compoundYield 56%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 8-bromo-7-(2-chloro-6-fluorobenzyl)-3-methyl-3,7-dihydro-1H-purine-2,6-dione (200 mg, 0.52 mmol) and K2CO3 (357 mg, 2.6 mmol) in 4 mL DMF was treated with iodoethane (412 μL, 5.2 mmol). The reaction was heated to 50° C. for 48 hr. The reaction mixture was cooled, diluted with H2O, and extracted 3× with 50% EtOAc:hexanes. The organic layers were combined and the solvent removed under reduced pressure (116 mg, 54% yield). The crude product (52 mg, 0.13 mmol) was dissolved in 200 μL DMSO and treated with piperidine (37 μL, 0.38 mmol). The reaction mixture was heated to 100° C. for 15 hr. The reaction mixture was cooled, diluted with H2O, and extracted 3× with 50% EtOAc:hexanes. The organic layers were combined, dried with Mg2SO4, and evaporated under reduced pressure. The crude product was purified by preparative thin layer chromatography (silica gel, 1 mm plate, EM Science 20×20 cm silica gel 60 F264) eluting with EtOAc:hexane (1:1) to give 31 mg (56% yield) of the title compound as a white solid: 1H NMR (CDCl3, 400 MHz) 7.21-7.14 (m, 1H), 7.13-7.09 (m, 1H), 6.96-6.90 (m, 1H), 5.53 (s, 2H), 3.96 (q, 2H, J=7.0 Hz), 3.49 (s, 3H), 3.09-3.00 (m, 4H), 1.54-1.46 (m, 6H), 1.13 (t, 3H, J=7.0 Hz); MS (ESP+) m/e 420 (MH+).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted 3× with 50% EtOAc
  3. customthe solvent removed under reduced pressure (116 mg, 54% yield)
  4. temperatureThe reaction mixture was heated to 100° C. for 15 hr
  5. temperatureThe reaction mixture was cooled
  6. extractionextracted 3× with 50% EtOAc
  7. dry with materialdried with Mg2SO4
  8. customevaporated under reduced pressure
  9. customThe crude product was purified by preparative thin layer chromatography (silica gel, 1 mm plate, EM Science 20×20 cm silica gel 60 F264)
  10. washeluting with EtOAc:hexane (1:1)

Sources & evidence

ORD record
ord-db159aba996743cdb30c566c8d1a4bbb
Source dataset
uspto-grants-2009_02
Patent number
US07495004B2

Reaction notes

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