Cesium carbonate → 4-(4-bromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amine

HRID 1091615Notes

Reaction equation

HRID 1091615 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([C:22]([CH3:25])([CH3:24])[CH3:23])[N:5]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9](Cl)[N:8]=1.[CH3:26][O:27][C:28]1[CH:33]=[C:32]([NH2:34])[CH:31]=[CH:30][N:29]=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+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[Br:1][C:2]1[N:3]=[C:4]([C:22]([CH3:25])([CH3:24])[CH3:23])[N:5]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:34][C:32]2[CH:31]=[CH:30][N:29]=[C:28]([O:27][CH3:26])[CH:33]=2)[N:8]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 2808912-Methoxypyridin-4-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866514104-(4-bromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine

Product 1

HCID 665912424-(4-bromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amineYield 65.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(4-bromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine (500 mg, 1.1 mmol; Example 6, Step 4), 2-methoxypyridin-4-amine (153 mg, 1.2 mmol), Pd(OAc)2 (30 mg, 0.14 mmol), XANTPHOS (117 mg, 0.20 mmol), cesium carbonate (731 mg, 2.2 mmol) in dry dioxane (9 ml) was sparged with N2 for 5 min. The reaction was sealed and heated at 100° C. for 2 hr. The reaction was allowed to cool to rt and partitioned between EtOAc and water. The layers were separated and the aqueous portion was extracted with EtOAc. The combined organic portions were dried (MgSO4) and concentrated to an orange residue which as purified by column chromatography (SiO2, 100:0-0:100, hexanes-EtOAc) to provide 386 mg of 4-(4-bromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amine: LCMS (m/z): 533.2 (MH+), tR=0.92 min.

Workup

  1. customwas sparged with N2 for 5 min
  2. customThe reaction was sealed
  3. temperatureto cool to rt
  4. custompartitioned between EtOAc and water
  5. customThe layers were separated
  6. extractionthe aqueous portion was extracted with EtOAc
  7. dry with materialThe combined organic portions were dried (MgSO4)
  8. concentrationconcentrated to an orange residue which
  9. customas purified by column chromatography (SiO2, 100:0-0:100, hexanes-EtOAc)

Sources & evidence

ORD record
ord-0cf6b5b5d5b14a7eb6e2cfceff67e6f3
Source dataset
uspto-grants-2012_03
Patent number
US08129394B2

Reaction notes

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