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

HRID 71569

반응식

HRID 71569 반응식
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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 174Ethylene Glycol용매

반응 조건

온도
185 °C

실험 절차

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: Rf 0.66 (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 cm−1; ESI MS m/z 411 [C22H23FN4O3+H]+; HPLC (Method A)>99% (AUC), tR=17.3 min. Anal. Calcd for C22H23FN4O3: C, 64.38; H, 5.65; N, 13.65. Found: C, 62.64; H, 5.59; N, 13.15.

후처리

  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)

출처 및 근거

ORD 기록
ord-ab7189789a534ce8b6bc292b022bc1f8
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822685B2

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