Iodoethane → HCID 10387391, compound

HRID 1727021Notes

Reaction equation

HRID 1727021 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])[N:7]([CH3:21])[C:6](=[O:22])[NH:5][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]([CH3:21])[C:6](=[O:22])[N:5]([CH2:30][CH3:31])[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 57565616HCID 57565616, compound

Product 1

HCID 10387391HCID 10387391, compoundYield 54%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

A solution of 8-bromo-7-(2-chloro-6-fluorobenzyl)-1-methyl-3,7-dihydro-1H-purine-2,6-dione (200 mg, 0.52 mmol) and K2CO3 (86 mg, 0.62 mmol) in 5.2 mL DMF was treated with iodoethane (412 μL, 5.2 mmol). The reaction was stirred at room temperature for 15 hr. The reaction mixture was diluted with H2O, and extracted 3× with 50% EtOAc:hexanes. The organic layers were combined and the solvent removed under reduced pressure (50 mg, 23% yield). The crude product (50 mg, 0.12 mmol) was dissolved in 200 μL DMSO and treated with piperidine (36 μL, 0.36 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 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 (2:3) to give 27 mg (54% yield) of the title compound as a white solid: 1H NMR (CDCl3, 400 MHz) 7.22-7.15 (m, 1H), 7.15-7.11 (m, 1H), 6.98-6.91 (m, 1H), 5.55 (s, 2H), 4.10 (q, 2H, J=7.1 Hz), 3.30 (s, 3H), 3.08-3.01 (m, 4H), 1.53-1.47 (m, 6H), 1.30 (t, 3H, J=7.1 Hz); MS (ESP+) m/e 420 (MH+); TLC (EtOAc:hexanes/1:2) Rf=0.24.

Workup

  1. extractionextracted 3× with 50% EtOAc
  2. customthe solvent removed under reduced pressure (50 mg, 23% yield)
  3. temperatureThe reaction mixture was heated to 100° C. for 15 hr
  4. temperatureThe reaction mixture was cooled
  5. extractionextracted 3× with 50% EtOAc
  6. customevaporated under reduced pressure
  7. customThe crude product was purified by preparative thin layer chromatography (silica gel, 1 mm plate, EM Science 20×20 cm silica gel 60 F264)
  8. washeluting with EtOAc:hexane (2:3)

Sources & evidence

ORD record
ord-c1f075d32e4f46d89630f89fb6eb4be0
Source dataset
uspto-grants-2009_02
Patent number
US07495004B2

Reaction notes

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