Cesium carbonate → 5-Bromo-3-(2-(2-hydroxypropan-2-yl)pyrimidin-4-ylamino)-1-methylpyridin-2(1H)-one

HRID 1022091Notes

Reaction equation

HRID 1022091 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([OH:11])([CH3:10])[CH3:9])[N:3]=1.Br[C:13]1[C:14](=[O:21])[N:15]([CH3:20])[CH:16]=[C:17]([Br:19])[CH:18]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Br:19][C:17]1[CH:18]=[C:13]([NH:1][C:2]2[CH:7]=[CH:6][N:5]=[C:4]([C:8]([OH:11])([CH3:9])[CH3:10])[N:3]=2)[C:14](=[O:21])[N:15]([CH3:20])[CH:16]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 866844992-(4-Aminopyrimidin-2-yl)propan-2-ol

Product 1

HCID 866845005-Bromo-3-(2-(2-hydroxypropan-2-yl)pyrimidin-4-ylamino)-1-methylpyridin-2(1H)-oneYield 30%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 264a (300 mg, 2.0 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (800 mg, 3.0 mmol), Pd2(dba)3 (182 mg, 0.20 mmol), XantPhos (231 mg, 0.40 mmol), Cs2CO3 (1.30 g, 4.0 mmol), and 1,4-dioxane (20 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 15 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica-gel column chromatography eluting with 40:1 dichloromethane/methanol (40:1) and further purified by reverse-phase Combiflash to afford 264b as white solid (200 mg, 30%). MS-ESI: [M+H]+ 339.0

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by silica-gel column chromatography
  7. washeluting with 40:1 dichloromethane/methanol (40:1)
  8. customfurther purified by reverse-phase Combiflash

Sources & evidence

ORD record
ord-61e64b6a6ccd4a7b91e410b355bdec0a
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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