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 538411

反応式

HRID 538411 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-ae80fab5652b4f25a6c815f1d1f9383a
出典データセット
uspto-grants-2014_10
特許番号
US08865732B2

関連ノート

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