Potassium Carbonate → HCID 135730636, compound

HRID 354197Notes

Reaction equation

HRID 354197 reaction equation
C(=O)([O-])[O-].[K+].[K+].Cl.Cl.[CH3:9][N:10]([CH3:20])[C:11]1[N:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.[C:21]([C:24]1[CH:25]=[C:26]([C:33]2[NH:34][C:35](=[O:44])[C:36]3[C:37](=[C:39](Br)[N:40]([CH3:42])[N:41]=3)[N:38]=2)[C:27]([O:30][CH2:31][CH3:32])=[N:28][CH:29]=1)(=[O:23])[CH3:22]>O1CCOCC1.O.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>[C:21]([C:24]1[CH:25]=[C:26]([C:33]2[NH:34][C:35](=[O:44])[C:36]3[C:37](=[C:39]([C:14]4[CH:15]=[N:16][C:11]([N:10]([CH3:20])[CH3:9])=[CH:12][CH:13]=4)[N:40]([CH3:42])[N:41]=3)[N:38]=2)[C:27]([O:30][CH2:31][CH3:32])=[N:28][CH:29]=1)(=[O:23])[CH3:22]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 44118205[6-(Dimethylamino)pyridin-3-yl]boronic acid--hydrogen chloride (1/2)2×HCID 135730618HCID 135730618, compound

Product 1

HCID 135730636HCID 135730636, compoundYield 53.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

Potassium carbonate (35 mg, 0.25 mmol), 6-(dimethylamino)pyridin-3-yl boronic acid dihydrochloride (42 mg, 0.25 mmol) and 5-(5-acetyl-2-ethoxy-3-pyridinyl)-3-bromo-2-methyl-2,6-dihydro-7H-pyrazolo[4,3-d]-pyrimidin-7-one (Example 58) (50 mg, 0.13 mmol) were suspended in dioxan/water (2 mL of a 4:1 mix) and the reaction mixture was immersed in a pre-heated oil bath (120° C.) for 5 min. The mixture was cooled and Pd(PPh3)4 (14 mg, 0.012 mmol) was added. The mixture was reheated to reflux for 2 h. More Pd(PPh3)4 (15 mg, 0.012 mmol) and 6-(dimethyl-amino)pyridin-3-yl boronic acid dihydrochloride (32 mg, 0.25 mmol) were added and reflux was continued for 14 h. The cooled reaction mixture was concentrated and the residue partitioned between dichloromethane and water and filtered through a plug of Celite®. The organic layer was washed with saturated sodium bicarbonate and brine, dried (MgSO4), filtered and evaporated. The yellow residual solid was purified by flash column chromatography (gradient elution from dichloromethane/0.2% ammonia to 99% dichloromethane/methanol/0.5% ammonia) to give 30 mg of the title compound. Further purification by trituration with ether and recrystallisation from isopropyl alcohol to give 18 mg of pure product.

Workup

  1. additionmix) and the reaction mixture
  2. customwas immersed in a pre-heated oil bath
  3. temperatureThe mixture was cooled
  4. temperatureto reflux for 2 h
  5. temperaturereflux
  6. waitwas continued for 14 h
  7. customThe cooled reaction mixture
  8. concentrationwas concentrated
  9. customthe residue partitioned between dichloromethane and water
  10. filtrationfiltered through a plug of Celite®
  11. washThe organic layer was washed with saturated sodium bicarbonate and brine
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. customevaporated
  15. customThe yellow residual solid was purified by flash column chromatography (gradient elution from dichloromethane/0.2% ammonia to 99% dichloromethane/methanol/0.5% ammonia)

Sources & evidence

ORD record
ord-a54e58ec14d34a2c86849e2add8fb8a0
Source dataset
uspto-grants-2004_06
Patent number
US06756373B1

Reaction notes

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