Tetrahydrofuran → HCID 90402827, compound

HRID 2200727Notes

Reaction equation

HRID 2200727 reaction equation
[Cl:1][C:2]1[CH:36]=[CH:35][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:17][C:18](=[O:20])[CH3:19])[C:12](=[O:21])[N:11]([CH3:22])[C:10]=3[N:9]=[C:8]2[O:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]([F:34])([F:33])[F:32])[CH:25]=2)=[CH:4][CH:3]=1.[CH2:37]([Mg]Br)[CH2:38]C.[CH2:42]1COCC1>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]([CH2:17][C:18]([OH:20])([CH3:42])[CH2:19][CH2:37][CH3:38])[C:12](=[O:21])[N:11]([CH3:22])[C:10]=3[N:9]=[C:8]2[O:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]([F:34])([F:32])[F:33])[CH:25]=2)=[CH:35][CH:36]=1

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 90402895HCID 90402895, compoundHCID 178455851HCID 178455851, compound

Product 1

HCID 90402827HCID 90402827, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

7-(4-Chlorobenzyl)-3-methyl-1-(2-oxopropyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (0.25 g, 0.48 mmol, example 348) was dissolved in THF (6 mL), cooled to 0° C. and 2.0 M propyl magnesium bromide in THF (0.36 mL, 0.72 mmol) was added drop wise. The reaction was stirred in the cold for 15 min then warmed to room temperature and stirred 1 h. The reaction was diluted with water (100 mL) and extracted with ethyl acetate (3×75 mL). The combined extracts were dried with magnesium sulfate, filtered and evaporated under reduced pressure to a golden oil. The oil was purified using a 25 g silica gel flash column eluted with 20% ethyl acetate/hexanes to give 7-(4-chlorobenzyl)-1-(2-hydroxy-2-methylpentyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (0.88 g, 32% yield) as a clear oil. LCMS retention time=4.792 minutes and 98% purity, LCMS MH+=567. 1H NMR (DMSO-d6) δ 7.59 (t, 1H, J=8 Hz), 7.47-7.50 (m, 1H), 7.38-7.44 (m, 5H), 7.31 (d, 1H, J=8 Hz), 5.42 (s, 2H), 4.23 (s, 1H) 3.92-4.02 (dd, 2H, J=4 Hz and 16 Hz), 3.29 (s, 3H), 1.30-1.41 (m, 4H), 0.99 (s, 3H), 0.80 (t, 3H, J=8 Hz).

Workup

  1. temperaturethen warmed to room temperature
  2. stirringstirred 1 h
  3. extractionextracted with ethyl acetate (3×75 mL)
  4. dry with materialThe combined extracts were dried with magnesium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure to a golden oil
  7. customThe oil was purified
  8. washeluted with 20% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-bd62ea5b8527499f8fda7b48647667e3
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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