Sodium Carbonate → 2-(5-Chloro-2-fluorophenyl)-5-methylpyrimidin-4-amine

HRID 1522558Notes

Reaction equation

HRID 1522558 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6](B(O)O)[CH:7]=1.Cl[C:13]1[N:18]=[C:17]([NH2:19])[C:16]([CH3:20])=[CH:15][N:14]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.[Cl-].[Na+].O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6]([C:13]2[N:18]=[C:17]([NH2:19])[C:16]([CH3:20])=[CH:15][N:14]=2)[CH:7]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 3718925(5-Chloro-2-fluoro-phenyl)boronic acidHCID 43021752-Chloro-5-methylpyrimidin-4-amine

Product 1

HCID 674696142-(5-Chloro-2-fluorophenyl)-5-methylpyrimidin-4-amine

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

trans-Dichlorobis(triphenylphosphine)palladium (II) (1.179 g, 1.680 mmol), 5-chloro-2-fluorophenylboronic acid (6.15 g, 35.3 mmol), 2-chloro-5-methylpyrimidin-4-amine (2.411 g, 16.80 mmol), were combined with 2M Na2CO3 (8.40 ml, 16.80 mmol) in dioxane (79 mL) and then heated at reflux for 1 hour. The reaction mixture was then cooled to room temperature and concentrated on a rotovap to afford a tan solid. The solid was suspended in brine (50 mL) and extracted with EtOAc (20 mL). The organic layer was dried over Na2SO4, filtered, and concentrated on a rotovap to afford an amber colored oil which was loaded onto silica (12 g) and purified by silica chromatography using a step gradient eluted with (10-75% ethyl acetate/hexanes) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.03 (3H, d, J=0.76 Hz) 6.85 (2H, br. s.) 7.31 (1H, dd, J=10.61, 8.84 Hz) 7.46-7.55 (1H, m) 7.88 (1H, dd, J=6.57, 3.03 Hz) 8.06 (1H, d, J=0.76 Hz). ESI-MS: m/z 238.1 (M+H).

Workup

  1. temperatureheated
  2. temperatureat reflux for 1 hour
  3. concentrationconcentrated on a rotovap
  4. customto afford a tan solid
  5. extractionextracted with EtOAc (20 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated on a rotovap
  9. customto afford an amber colored oil which
  10. custompurified by silica chromatography
  11. washeluted with (10-75% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-adca479a39d94c56b4865a00ca5ef992
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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