4-Butyloxyaniline → N2-(4-n-Butyloxyphenyl)-N4-(3,4-ethylenedioxyphenyl)-5-fluoro-2,4-pyridinediamine

HRID 226836

反応式

HRID 226836 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]3[O:15][CH2:16][CH2:17][O:18][C:11]=3[CH:10]=2)[C:5]([F:19])=[CH:4][N:3]=1.[CH:20](N(CC)C(C)C)(C)C.[CH2:29]([O:33][C:34]1[CH:40]=[CH:39][C:37](N)=[CH:36][CH:35]=1)[CH2:30][CH2:31][CH3:32]>C(O)CO>[CH2:29]([O:33][C:34]1[CH:40]=[CH:39][C:37]([NH:7][C:2]2[CH:20]=[C:6]([NH:8][C:9]3[CH:14]=[CH:13][C:12]4[O:15][CH2:16][CH2:17][O:18][C:11]=4[CH:10]=3)[C:5]([F:19])=[CH:4][N:3]=2)=[CH:36][CH:35]=1)[CH2:30][CH2:31][CH3:32]

参加物

5

反応物 3

HCID 203524-ButyloxyanilineHCID 81531DiisopropylethylamineHCID 220603622-chloro-5-fluoro-N-(3,4-ethylenedioxyphenyl)-4-pyrimidineamine

生成物 1

HCID 22060376N2-(4-n-Butyloxyphenyl)-N4-(3,4-ethylenedioxyphenyl)-5-fluoro-2,4-pyridinediamine収率 49.4%

試薬・触媒・溶媒 1

HCID 174Ethylene Glycol溶媒

反応条件

温度
185 °C

実験手順

To a magnetically stirred solution of 2-chloro-N4-(3,4-ethylenedioxyphenyl)-5-fluoro-4-pyrimidineamine (0.25 g, 0.89 mmol) in ethylene glycol (3.0 mL) under nitrogen at room temperature was added N,N-diisopropylethylamine (0.12 g, 0.89 mmol) followed by 4-butoxyaniline (0.18 g, 1.1 mmol). The reaction mixture was heated to 185° C. for 5 h, cooled to room temperature, and partitioned between water (20 mL) and ethyl acetate (20 mL). The aqueous layer was extracted with ethyl acetate (20 mL) and the combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The crude brown solid was purified by chromatography (silica gel, 2:1 hexanes/ethyl acetate) to afford N2-(4-n-Butyloxyphenyl)-N4-(3,4-ethylenedioxyphenyl)-5-fluoro-2,4-pyridinediamine (0.18 g, 49%) as a tan solid: Rf0.66 (silica gel, 4:1 chloroform/ethyl acetate); mp 133–135° C.; 1H NMR (300 MHz, CDCl3) δ 7.89 (d, J=3.2 Hz, 1H), 7.39 (d, J=8.9 Hz, 2H), 7.28 (d, J=2.5 Hz, 1H), 6.95 (dd, J=8.7, 2.5 Hz, 1H) 6.90–6.81 (m, 4H), 6.60 (d, J=2.4 Hz, 1H), 4.27 (s, 4H), 3.94 (t, J=6.5 Hz, 2H), 1.80–1.71 (m, 2H), 1.55–1.42 (m, 2H), 0.97 (t, J=7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 156.3, 155.1, 150.4, 143.6, 142.7, 140.3, 140.0, 139.4, 133.0, 131.7, 121.9, 117.3, 115.0, 114.7, 110.8, 68.2, 64.7, 64.5, 31.6, 19.4, 14.0; IR (ATR) 3356 cm1; ESI MS m/z 411 [C22H23FN4O3+H]+; HPLC (Method A)>99% (AUC), tR=17.3 mm. Anal. Calcd for C22H23FN4O3: C, 64.38; H, 5.65; N, 13.65. Found C, 62.64; H, 5.59; N, 13.15.

後処理

  1. temperaturecooled to room temperature
  2. custompartitioned between water (20 mL) and ethyl acetate (20 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
  4. dry with materialthe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude brown solid was purified by chromatography (silica gel, 2:1 hexanes/ethyl acetate)

出典と根拠

ORDレコード
ord-bf5668fea8484daaacdc74b2a5bf2d26
出典データセット
uspto-grants-2009_07
特許番号
US07557210B2

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