Chloroacetone → HCID 90402895, compound

HRID 2200725Notes

Reaction equation

HRID 2200725 reaction equation
[Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[NH:13][C:12](=[O:17])[N:11]([CH3:18])[C:10]=3[N:9]=[C:8]2[O:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]([F:30])([F:29])[F:28])[CH:21]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:40][C:41](=[O:43])[CH3:42]>CCCC[N+](CCCC)(CCCC)CCCC.[I-].CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:40][C:41](=[O:43])[CH3:42])[C:12](=[O:17])[N:11]([CH3:18])[C:10]=3[N:9]=[C:8]2[O:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]([F:30])([F:28])[F:29])[CH:21]=2)=[CH:31][CH:32]=1

Participants

7

Reactant 3

HCID 6571ChloroacetoneHCID 11430Potassium CarbonateHCID 90403003HCID 90403003, compound2×

Product 1

HCID 90402895HCID 90402895, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

7-(4-Chlorobenzyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (0.25 g, 0.54 mmol, intermediate 9), potassium carbonate (0.11 g, 0.80 mmol), TBAI (0.10 g) and 1-chloropropan-2-one (0.040 mL, 0.59 mmol) were combined in DMF (3 mL) and heated at 50° C. for 1.5 h. The reaction was cooled to room temperature, diluted with water (100 mL) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were washed with 1N lithium chloride (2×75 mL) dried with magnesium sulfate, filtered and evaporated under reduced pressure to an off-white solid. The solid was purified using a 25 g silica gel flash column eluted with 1% methanol/DCM to give 7-(4-chlorobenzyl)-3-methyl-1-(2-oxopropyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (0.22 g, 79% yield) as a white solid. LCMS retention time 4.433 minutes and 99% purity, LCMS MH+ 523. 1H NMR (DMSO-d6) δ 7.60 (t, 1H, J=8 Hz), 7.50-7.53 (m, 1H), 7.38-7.47 (m, 5H), 7.32 (d, 1H, J=8 Hz), 5.40 (s, 2H), 4.73 (s, 2H) 3.28 (s, 3H), 2.19 (s, 3H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. extractionextracted with ethyl acetate (3×75 mL)
  3. washThe combined organic extracts were washed with 1N lithium chloride (2×75 mL)
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure to an off-white solid
  7. customThe solid was purified
  8. washeluted with 1% methanol/DCM

Sources & evidence

ORD record
ord-e9ad4be4f6ee46ee875af6a940f923da
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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