Potassium Carbonate → 5-{2-Butoxy-5-[3-(trifluoromethyl)phenyl]-3-pyridinyl}-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7h-pyrazolo[4,3-d]pyrimidin-7-one

HRID 354172Notes

Reaction equation

HRID 354172 reaction equation
[CH2:1]([O:5][C:6]1[C:11]([C:12]2[NH:13][C:14](=[O:27])[C:15]3[C:16](=[C:18]([CH2:25][CH3:26])[N:19]([CH2:21][CH2:22][O:23][CH3:24])[N:20]=3)[N:17]=2)=[CH:10][C:9](I)=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4].C([O-])([O-])=O.[K+].[K+].B(O)(O)[C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([F:45])([F:44])[F:43])[CH:37]=1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:5][C:6]1[C:11]([C:12]2[NH:13][C:14](=[O:27])[C:15]3[C:16](=[C:18]([CH2:25][CH3:26])[N:19]([CH2:21][CH2:22][O:23][CH3:24])[N:20]=3)[N:17]=2)=[CH:10][C:9]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([F:45])([F:44])[F:43])[CH:37]=2)=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 1354560315-(2-Butoxy-5-iodo-3-pyridinyl)-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

Product 1

HCID 1357306445-{2-Butoxy-5-[3-(trifluoromethyl)phenyl]-3-pyridinyl}-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7h-pyrazolo[4,3-d]pyrimidin-7-oneYield 70%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

5-(2-Butoxy-5-iodo-3-pyridinyl)-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (Example 1) (140 mg, 0.28 mmol), K2CO3 (78 mg, 0.56 mmol) and 3-trifluoromethylboronic acid (60 mg, 0.34 mmol) were stirred together in aqueous dioxan under a nitrogen atmosphere. The mixture was immersed in a pre-heated oil bath at 120° C. for a few minutes and Pd(PPh3)4 (34 mg, 0.028 mmol) was added. The mixture was heated at reflux for 2 h and then cooled. The cooled mixture was concentrated and partitioned between ethyl acetate and water. This was then filtered through an Arbocel® pad to remove the palladium residues and the organic layer separated, washed with sodium bicarbonate solution then brine, dried (MgSO4) and concentrated. Recrystallisation from ethyl acetate gave the title compound (101 mg, 70%).

Workup

  1. waitThe mixture was immersed in a pre-heated oil bath at 120° C. for a few minutes
  2. temperatureThe mixture was heated
  3. temperatureat reflux for 2 h
  4. temperaturecooled
  5. concentrationThe cooled mixture was concentrated
  6. custompartitioned between ethyl acetate and water
  7. filtrationThis was then filtered through an Arbocel® pad
  8. customto remove the palladium residues
  9. customthe organic layer separated
  10. washwashed with sodium bicarbonate solution
  11. dry with materialbrine, dried (MgSO4)
  12. concentrationconcentrated
  13. customRecrystallisation from ethyl acetate

Sources & evidence

ORD record
ord-fa7e0f3b7abf4ea8897a81890f16500f
Source dataset
uspto-grants-2004_06
Patent number
US06756373B1

Reaction notes

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