Water → 4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carboxylic acid

HRID 2105686Notes

Reaction equation

HRID 2105686 reaction equation
C[O:2][C:3]([C:5]12[CH2:12][CH2:11][C:8]([C:13](=O)[NH:14][C:15]3[C:16](=[O:29])[N:17]([CH2:26][CH2:27][CH3:28])[C:18](=[O:25])[N:19]([CH2:22][CH2:23][CH3:24])[C:20]=3[NH2:21])([CH2:9][CH2:10]1)[CH2:7][CH2:6]2)=[O:4].C(O)(C)C.[OH-].[K+].O>C1(C)C=CC=CC=1>[O:25]=[C:18]1[N:19]([CH2:22][CH2:23][CH3:24])[C:20]2[N:21]=[C:13]([C:8]34[CH2:11][CH2:12][C:5]([C:3]([OH:2])=[O:4])([CH2:10][CH2:9]3)[CH2:6][CH2:7]4)[NH:14][C:15]=2[C:16](=[O:29])[N:17]1[CH2:26][CH2:27][CH3:28]

Participants

6

Reactant 4

HCID 962WaterHCID 3776IsopropanolHCID 14797Potassium HydroxideHCID 865917464-(6-Amino-2,4-dioxo-1,3-dipropyl-1,2,3,4-tetrahydropyrimidin-5-ylcarbamoyl)bicyclo[2.2.2]octane-1-carboxylic acid methyl ester

Product 1

HCID 98865894-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carboxylic acid

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
17.5 °C

Procedure

4-(6-Amino-2,4-dioxo-1,3-dipropyl-1,2,3,4-tetrahydro-pyrimidin-5-ylcarbamoyl)-bicyclo[2.2.2]octane-1-carboxylic acid methyl ester (VII, Example 83b, 0.760 kg) and isopropanol (3.62 l) are combined. The mixture is stirred under nitrogen and potassium hydroxide (2 M, 3.62 l) is added. The contents are heated at reflux for 3 hr (test for reaction completion by NMR). The mixture is then allowed to cool to 10 to 25° C. Water (8.48 l) is added followed by toluene (0.95 l) and the contents are stirred vigorously for 5 to 15 minutes. The layers are separated. Extraction with toluene (0.95 l) is performed two additional times. The aqueous phase is then cooled to between 0 and 10° C. and acidified with concentrated hydrochloric acid (0.562 l). The mixture is stirred at between 0 and 10° C. for 60 minutes. Solid product is collected by filtration and dried under reduced pressure at 50 to 60° C. to give the title compound.

Workup

  1. temperatureThe contents are heated
  2. temperatureat reflux for 3 hr
  3. custom(test for reaction completion by NMR)
  4. stirringthe contents are stirred vigorously for 5 to 15 minutes
  5. customThe layers are separated
  6. extractionExtraction with toluene (0.95 l)
  7. temperatureThe aqueous phase is then cooled to between 0 and 10° C.
  8. stirringThe mixture is stirred at between 0 and 10° C. for 60 minutes
  9. filtrationSolid product is collected by filtration
  10. customdried under reduced pressure at 50 to 60° C.

Sources & evidence

ORD record
ord-9b9a2df4b5e24363b07796abff911b1c
Source dataset
uspto-grants-2009_08
Patent number
US07579354B2

Reaction notes

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