Cesium carbonate → 6-(4-Chloropyridin-3-yl)-2-methylpyrimidin-4-amine

HRID 1811897Notes

Reaction equation

HRID 1811897 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1B1OC(C)(C)C(C)(C)O1.Cl[C:18]1[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([NH2:25])[CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.[NH4+].[Cl-].[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[C:18]1[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([NH2:25])[CH:19]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 2867546-Chloro-2-methylpyrimidin-4-amineHCID 120670644-Chloropyridine-3-boronic acid, pinacol ester

Product 1

HCID 666002046-(4-Chloropyridin-3-yl)-2-methylpyrimidin-4-amineYield 15%

Reagents, catalysts & solvents 4

HCID 178478230HCID 178478230, compoundCatalystHCID 962WaterSolventHCID 25517Ammonium ChlorideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (239 mg, 998 μmol, Combi-Blocks, Inc., San Diego, Calif.), 6-chloro-2-methylpyrimidin-4-amine (143 mg, 998 μmol), dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium (II) (81 mg, 100 μmol), cesium carbonate (160 μl, 1996 μmol) in dioxane (2 mL) and water (0.5 mL) was stirred at 100° C. for 10 min. The mixture was cooled down to room temperature. The reaction mixture was diluted with saturated NH4Cl (5 mL) and extracted with EtOAc (2×30 mL). The organic extract was washed with saturated NaCl (5 mL), dried over Na2SO4, filtered, concentrated in vacuo and the residue was purified by silica gel chromatography, eluting with THF to give 6-(4-chloropyridin-3-yl)-2-methylpyrimidin-4-amine (32 mg, 15% yield). 1H NMR (300 MHz, MeOH) δ 8.66 (s, 1H); 8.57 (d, J=5.41 Hz, 1H); 7.66 (d, J=5.26 Hz, 1H); 6.64 (s, 1H); 2.04 (s, 3H). m/z (ESI, +ve ion) 221 (M+H)+.

Workup

  1. temperatureThe mixture was cooled down to room temperature
  2. extractionextracted with EtOAc (2×30 mL)
  3. extractionThe organic extract
  4. washwas washed with saturated NaCl (5 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthe residue was purified by silica gel chromatography
  9. washeluting with THF

Sources & evidence

ORD record
ord-2882fe36907c4c509ebf637ec17d5184
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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