Tetrahydrofuran → 2-(2,5-Dimethyl-1H-pyrrol-1-yl)-4-methyl-8-(pyrrolidin-1-yl)pyrido[2,3-d]pyrimidin-7(8H)-one

HRID 2390004Notes

Reaction equation

HRID 2390004 reaction equation
Br[C:2]1[C:3]([N:16]([N:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)[C:17](=[O:20])[CH:18]=[CH2:19])=[N:4][C:5]([N:9]2[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]2[CH3:15])=[N:6][C:7]=1[CH3:8].C1COCC1>[Cl-].[Na+].O>[CH3:15][C:10]1[N:9]([C:5]2[N:6]=[C:7]([CH3:8])[C:2]3[CH:19]=[CH:18][C:17](=[O:20])[N:16]([N:21]4[CH2:25][CH2:24][CH2:23][CH2:22]4)[C:3]=3[N:4]=2)[C:13]([CH3:14])=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 59258866N-(5-Bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-methylpyrimidin-4-yl)-N-(pyrrolidin-1-yl)acrylamide

Product 1

HCID 592589832-(2,5-Dimethyl-1H-pyrrol-1-yl)-4-methyl-8-(pyrrolidin-1-yl)pyrido[2,3-d]pyrimidin-7(8H)-one

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
70 °C

Procedure

To a microwave vial was added N-(5-bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-methylpyrimidin-4-yl)-N-(pyrrolidin-1-yl)acrylamide (2.0 g, 4.95 mmol) silver carbonate (2.73 g, 9.89 mmol) and anhydrous THF (100 ml). The reaction suspension was bubbled in nitrogen for 2 mins and then added the palladium tetrakis tert-(triphenylphosphine) (286 mg, 0.25 mmol). After stirring at 70° C. oil bath for 3 h, the reaction mixture was cooled to R.T. and diluted with 20 ml of brine. After stirring at R.T. for 5 mins, the reaction mixture was filtered through a celite pad. The cake was washed with ethyl acetate. The layers were separated. The organic layer was washed with brine 20 ml, dried with potassium carbonate, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography eluted with 40% etoac:hex to give the titled compound weighted 480 mg 30%

Workup

  1. customThe reaction suspension was bubbled in nitrogen for 2 mins
  2. temperaturethe reaction mixture was cooled to R.T.
  3. stirringAfter stirring at R.T. for 5 mins
  4. filtrationthe reaction mixture was filtered through a celite pad
  5. washThe cake was washed with ethyl acetate
  6. customThe layers were separated
  7. washThe organic layer was washed with brine 20 ml
  8. dry with materialdried with potassium carbonate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue was purified by column chromatography
  12. washeluted with 40% etoac

Sources & evidence

ORD record
ord-44cf236a7e7b4755bfd0069f85a2091b
Source dataset
uspto-grants-2012_09
Patent number
US08273755B2

Reaction notes

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