Ammonium formate → 3-ethyl-1-(3-hydroxypropyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione

HRID 2200686Notes

Reaction equation

HRID 2200686 reaction equation
C([N:8]1[C:16]2[C:15](=[O:17])[N:14]([CH2:18][CH2:19][CH2:20][OH:21])[C:13](=[O:22])[N:12]([CH2:23][CH3:24])[C:11]=2[N:10]=[C:9]1[O:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([O:32][C:33]([F:36])([F:35])[F:34])[CH:27]=1)C1C=CC=CC=1.C([O-])=O.[NH4+]>C(O)C.[Pd]>[CH2:23]([N:12]1[C:11]2[N:10]=[C:9]([O:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([O:32][C:33]([F:35])([F:36])[F:34])[CH:27]=3)[NH:8][C:16]=2[C:15](=[O:17])[N:14]([CH2:18][CH2:19][CH2:20][OH:21])[C:13]1=[O:22])[CH3:24]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 904023497-benzyl-3-ethyl-1-(3-hydroxypropyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione

Product 1

HCID 904027233-ethyl-1-(3-hydroxypropyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dioneYield 117.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

7-benzyl-3-ethyl-1-(3-hydroxypropyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (0.62 g, 1.23 mmol, example 60) was dissolved in ethanol (20 mL); then the mixture was degassed and refilled with nitrogen three times. Ammonium formate (0.5 g, 7.94 mmol) and 10% Pd/C (30 mg) were added. The mixture was again degassed and refilled with nitrogen three times; then it was stirred at 80° C. overnight. The reaction was cooled and filtered. The filter cake was washed with methanol. The filtrate was concentrated to give 3-ethyl-1-(3-hydroxypropyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (0.6 g, 100% yield) as white solid. 1H-NMR (DMSO-d6) δ 7.61-7.57(t, 1H), 7.50(s, 1H), 7.40-7.38(dd, 1H), 7.31-7.29(d, 1H), 4.50(s, 1H), 3.95-3.85(m, 4H), 3.44-3.43(m, 2H), 1.73-1.66(t, 2H), 1.17-1.13(t, 3H). LCMS retention time 1.350 min; LCMS MH+ 415.

Workup

  1. customthen the mixture was degassed
  2. additionrefilled with nitrogen three times
  3. customThe mixture was again degassed
  4. additionrefilled with nitrogen three times
  5. temperatureThe reaction was cooled
  6. filtrationfiltered
  7. washThe filter cake was washed with methanol
  8. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-3c4e9b4f71d34749bae3ce3224f7e5b1
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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