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

HRID 12749

Reaction equation

HRID 12749 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.[F: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>[C:1]([N:9]1[C:14](=[O:15])[C:13]([C:29]2[C:24]([F: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

7

Reactant 4

HCID 10340Sodium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 27832702-Fluoropyridine-3-boronic acidHCID 589941523-Benzoyl-1-(4-chloro-butyl)-5-iodo-1H-pyrimidine-2,4-dione

Product 1

HCID 451178293-Benzoyl-1-(4-chloro-butyl)-5-(2-fluoro-pyridin-3-yl)-1H-pyrimidine-2,4-dioneYield 54.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

3-Benzoyl-1-(4-chloro-butyl)-5-iodo-1H-pyrimidine-2,4-dione (Prep129, 614 mg, 1.42 mmol) was dissolved in degassed DME-water solution (5-1, 35 ml). 2-Fluoro-pyridine 3-boronic acid (250 mg, 1.77 mmol), Na2CO3 (301 mg, 2.84 mmol), 2-(dicyclohexylphosphino)biphenyl (99 mg, 0.28 mmol) and Pd(PPh3)4 (328 mg, 0.28 mmol) were added and the mixture was refluxed for 3 hours. The solvents were evaporated under vacuum and the crude was partitioned between ethyl acetate and water. The organic phase was dried (Na2SO4) and evaporated; the crude (0.9 g, yellow oil) was purified by flash chromatography with ethyl acetate-petroleum ether (1-1) to give the title compound as yellow oil (310 mg, 54% yield).

Workup

  1. temperaturethe mixture was refluxed for 3 hours
  2. customThe solvents were evaporated under vacuum
  3. customthe crude was partitioned between ethyl acetate and water
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. customevaporated
  6. customthe crude (0.9 g, yellow oil) was purified by flash chromatography with ethyl acetate-petroleum ether (1-1)

Sources & evidence

ORD record
ord-f36738d46a914d64adcb7ef95c50ccd4
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Linked notes

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