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

HRID 1522568Notes

Reaction equation

HRID 1522568 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]([CH2:20]F)=[CH:15][N:14]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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

6

Reactant 3

HCID 10340Sodium CarbonateHCID 3718925(5-Chloro-2-fluoro-phenyl)boronic acidHCID 867043652-Chloro-5-fluoromethylpyrimidin-4-amine

Product 1

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

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

trans-Dichlorobis(triphenylphosphine)palladium (II) (1.179 g, 1.680 mmol), 5-chloro-2-fluorophenylboronic acid (6.1 g, 35.3 mmol), 2-chloro-5-fluoromethylpyrimidin-4-amine (2.411 g, 16.80 mmol), 2M Na2CO3 (8.40 mL, 16.80 mmol) were combined in dioxane (79 mL) and refluxed for 1 hour. The reaction was cooled, concentrated and the solids were suspended in brine (50 mL) and then extracted with EtOAc (20 mL). The layers were separated, the organics were dried over Na2SO4, filtered and concentrated to give a residue which was passed through a silica plug (12 g) to give 2-(5-chloro-2-fluorophenyl)-5-methylpyrimidin-4-amine which was without further purification. 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. temperaturerefluxed for 1 hour
  2. temperatureThe reaction was cooled
  3. concentrationconcentrated
  4. extractionextracted with EtOAc (20 mL)
  5. customThe layers were separated
  6. dry with materialthe organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a residue which

Sources & evidence

ORD record
ord-2a89c29a3d3b45e683111a3f6d19ae7b
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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