Dichloromethane → 6-(2-Fluoropyridin-3-yl)-2-methylpyrimidin-4-amine

HRID 1621875

反応式

HRID 1621875 の反応式
Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH2:9])[CH:3]=1.[F:10][C:11]1[C:16](B(O)O)=[CH:15][CH:14]=[CH:13][N:12]=1.ClCCl.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O>[F:10][C:11]1[C:16]([C:2]2[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH2:9])[CH:3]=2)=[CH:15][CH:14]=[CH:13][N:12]=1

参加物

7

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 2867546-Chloro-2-methylpyrimidin-4-amineHCID 27832702-Fluoropyridine-3-boronic acid

生成物 1

HCID 665999906-(2-Fluoropyridin-3-yl)-2-methylpyrimidin-4-amine収率 24.4%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

A mixture of 6-chloro-2-methyl-4-pyrimidinamine (SynChem, Inc., Des Plaines, Ill.) (0.500 g, 3.48 mmol), 2-fluoropyridin-3-ylboronic acid (0.589 g, 4.18 mmol), PdCl2 (dppf) complex with dichloromethane (0.199 g, 0.244 mmol) and 2 M Na2CO3 (aq., 5.22 mL, 10.45 mmol) in dioxane (17 mL) was stirred at 110° C. overnight. After cooling to RT, water was added and the mixture was filtered through Celite® (diatomaceous earth). The mixture was extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a silica gel column (40 g), eluting with a gradient of 0% to 5% MeOH in CH2Cl2, to provide 6-(2-fluoro-3-pyridinyl)-2-methyl-4-pyrimidinamine (0.173 g, 0.85 mmol, 24% yield) as an off-white solid. m/z (ESI, +ve) 205.1 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 8.52-8.62 (m, 1H); 8.27-8.34 (m, 1H); 7.44-7.61 (m, 2H); 7.00 (br. s., 1H); 6.75-6.83 (m, 1H); 2.39 (s, 3H).

後処理

  1. temperatureAfter cooling to RT
  2. filtrationthe mixture was filtered through Celite® (diatomaceous earth)
  3. extractionThe mixture was extracted with EtOAc (3×)
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by chromatography through a silica gel column (40 g)
  8. washeluting with a gradient of 0% to 5% MeOH in CH2Cl2

出典と根拠

ORDレコード
ord-b467e5a1609e49379f699786237547a9
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

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