6-Methoxy-3-pyridinylamine → 2-chloro-5-iodo-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine

HRID 1621515ノート

反応式

HRID 1621515 の反応式
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([I:9])=[CH:4][N:3]=1.[NH2:10][C:11]1[CH:12]=[CH:13][C:14]([O:17][CH3:18])=[N:15][CH:16]=1.C(N(CC)C(C)C)(C)C>O1CCOCC1.O.[Cu]I>[Cl:1][C:2]1[N:7]=[C:6]([NH:10][C:11]2[CH:16]=[N:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:5]([I:9])=[CH:4][N:3]=1

参加物

7

反応物 3

HCID 811216-Methoxy-3-pyridinylamineHCID 81531DiisopropylethylamineHCID 2634382,4-Dichloro-5-iodopyrimidine

生成物 1

HCID 866470532-chloro-5-iodo-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine収率 67%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A mixture of 2,4-dichloro-5-iodopyrimidine (274 mg, 0.997 mmol), 5-amino-2-methoxypyridine (0.247 mL, 1.994 mmol), N,N-diisopropylethylamine (0.347 mL, 1.994 mmol) and copper(I) iodide (38 mg, 0.199 mmol) in dioxane (2 mL) was stirred at 100° C. for 3 h. The mixture was cooled down to room temperature. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2×30 mL). The organic extract was washed with saturated NaCl (10 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as orange oil. The crude product was purified by silica gel chromatography eluting with 40% EtOAc/hexanes to give 2-chloro-5-iodo-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine (242 mg, 0.667 mmol, 67.0% yield). 1H NMR (300 MHz, CDCl3) δ 8.44 (s, 1H); 8.28 (d, J=1.90 Hz, 1H); 7.83 (dd, J=8.84, 2.56 Hz, 1H); 7.01 (s, 1H); 6.81 (d, J=8.77 Hz, 1H); 3.96 (s, 3H). m/z (ESI, +ve ion) 362.9 (M+H)+.

後処理

  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 (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as orange oil
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 40% EtOAc/hexanes

出典と根拠

ORDレコード
ord-085ad31bc6314f528d71906b34f844d9
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

反応ノート

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