Sodium Carbonate → 3-Benzoyl-1-(4-chloro-butyl)-5-(2-methyl-pyridin-3-yl)-1H-pyrimidine-2,4-dione

HRID 12679

Reaction equation

HRID 12679 reaction equation
[C:1]([N:9]1[C:14](=[O:15])[C:13](I)=[CH:12][N:11]([CH2:17][CH2:18][CH2:19][CH2:20][Cl:21])[C:10]1=[O:22])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23][C:24]1[C:29](B(O)O)=[CH:28][CH:27]=[CH:26][N:25]=1.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>COCCOC.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.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>[C:1]([N:9]1[C:14](=[O:15])[C:13]([C:29]2[C:24]([CH3:23])=[N:25][CH:26]=[CH:27][CH:28]=2)=[CH:12][N:11]([CH2:17][CH2:18][CH2:19][CH2:20][Cl:21])[C:10]1=[O:22])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 10340Sodium Carbonate2×HCID 27342162-(Dicyclohexylphosphino)biphenylHCID 201116472-Methylpyridine-3-boronic acid2×HCID 589941523-Benzoyl-1-(4-chloro-butyl)-5-iodo-1H-pyrimidine-2,4-dione

Product 1

HCID 451178303-Benzoyl-1-(4-chloro-butyl)-5-(2-methyl-pyridin-3-yl)-1H-pyrimidine-2,4-dioneYield 66.4%

Reagents, catalysts & solvents 3

HCID 27342162-(Dicyclohexylphosphino)biphenylCatalystHCID 178418397HCID 178418397, compoundCatalyst2×HCID 18180031Water 1,2-dimethoxyethaneSolvent2×

Procedure

3-Benzoyl-1-(4-chloro-butyl)-5-iodo-1H-pyrimidine-2,4-dione (Prep 44, 541 mg, 1.25 mmol) was dissolved in degassed DME-water solution (5-1, 37.5 mL). 2-Methyl-pyridine 3-boronic acid (325 mg, 1.9 mmol), Na2CO3 (265 mg, 2.5 mmol), 2-(dicyclohexylphosphino)biphenyl (52 mg, 0.15 mmol) and Pd(PPh3)4 (288 mg, 0.25 mmol) were added and the mixture was refluxed for 3 hours. A second batch was run in parallel in the same reaction conditions on 3-Benzoyl-1-(4-chloro-butyl)-5-iodo-1H-pyrimidine-2,4-dione (Prep 44, 108 mg, 0.25 mmol) using 2-Methyl-pyridine 3-boronic acid (65 mg, 0.375 mmol), Na2CO3 (53 mg, 0.5 mmol), 2-(dicyclohexylphosphino)biphenyl (17.5 mg, 0.05 mmol) and Pd(PPh3)4 (57.75 mg, 0.05 mmol) dissolved in degassed DME-water solution (5-1, 7.5 mL). The crudes were then mixed and the solvents were evaporated under vacuum and the residue was partitioned between ethyl acetate and water. The organic phase was dried (Na2SO4) and evaporated; the crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2) and then loaded on SCX cartridge washing with MeOH and eluting with MeOH/NH3 95:5 to give the title compound (330 mg, 56% yield).

Workup

  1. temperaturethe mixture was refluxed for 3 hours
  2. customparallel in the same reaction conditions on 3-Benzoyl-1-(4-chloro-butyl)-5-iodo-1H-pyrimidine-2,4-dione (Prep 44, 108 mg, 0.25 mmol)
  3. additionThe crudes were then mixed
  4. customthe solvents were evaporated under vacuum
  5. customthe residue was partitioned between ethyl acetate and water
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. customevaporated
  8. customthe crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2)
  9. washwashing with MeOH
  10. washeluting with MeOH/NH3 95:5

Sources & evidence

ORD record
ord-bf93c613eb994ddbbb7ea5a73a4f3a52
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Linked notes

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