Diisopropylethylamine → N4-(4-ethoxyphenyl)-N2-(3,4-ethylenedioxyphenyl)-5-fluoro-2,4-pyrimidinediamine

HRID 76681

Reaktionsgleichung

Reaktionsgleichung von HRID 76681
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH3:17])=[CH:11][CH:10]=2)[C:5]([F:18])=[CH:4][N:3]=1.C(N(C(C)C)C(C)C)C.[CH2:28]1[CH2:38][O:37][C:36]2[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][C:30]=2[O:29]1>C(O)CO>[CH2:16]([O:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][C:6]2[C:5]([F:18])=[CH:4][N:3]=[C:2]([NH:33][C:32]3[CH:34]=[CH:35][C:36]4[O:37][CH2:38][CH2:28][O:29][C:30]=4[CH:31]=3)[N:7]=2)=[CH:10][CH:11]=1)[CH3:17]

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 891481,4-Benzodioxan-6-ylamineHCID 220606042-chloro-N4-(4-ethoxyphenyl)-5-fluoro-4-pyrimidineamine

Produkt 1

HCID 22060247N4-(4-ethoxyphenyl)-N2-(3,4-ethylenedioxyphenyl)-5-fluoro-2,4-pyrimidinediamineAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 174Ethylene GlycolLösungsmittel

Reaktionsbedingungen

Temperatur
200 °C

Versuchsvorschrift

To a solution of 2-chloro-N4-(4-ethyloxyphenyl)-5-fluoro-4-pyrimidineamine (0.25 g, 0.93 mmol) in ethylene glycol (3 mL) under nitrogen at room temperature was added i-Pr2EtN, 0.93 mmol) followed by 3,4-ethylenedioxyaniline (0.17 g, 1.12 mmol). The reaction mixture was heated to 200° C. for 5 h and then cooled to room temperature. The mixture was partitioned between H2O (20 mL) and EtOAc (20 mL) and the aqueous layer was extracted with EtOAc (20 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude brown solid was purified by chromatography (2:1 CHCl3/EtOAc) to afford N4-(4-ethyloxyphenyl)-N2-(3,4-ethylenedioxyphenyl)-5-fluoro-2,4-pyrimidinediamine (0.21 g, 60%) as a tan solid: Rf 0.42 (4:1 CHCl3/EtOAc); mp 163.8-167.2° C. (DSC); 1H NMR (300 MHz, CDCl3) δ 7.89 (d, J=2.8 Hz, 1H), 7.50-7.45 (m, 2H), 7.17 (d, J=2.5 Hz, 1H), 6.92-6.86 (m, 3H), 6.80-6.75 (m, 2H), 6.64 (bs, 1H), 4.26-4.21 (m, 4H), 4.03 (q, J=7.0, 2H), 1.42 (t, J=6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 156.1, 150.6, 143.6, 142.8, 140.3, 140.0, 139.5, 139.3, 134.0, 130.8, 123.2, 117.2, 115.1, 113.6, 109.4, 64.6, 64.0, 15.1; IR (ATR) 3403 cm−1; ESI MS m/z 383 [C20H19FN4O3+H]+; HPLC (Method A) 98.1% (AUC), tR=12.0 min. Anal. Calcd for C20H19FN4O3: C, 62.82; H, 5.01; N, 14.65. Found: C, 62.06; H, 5.01; N, 14.35.

Aufarbeitung

  1. temperaturecooled to room temperature
  2. customThe mixture was partitioned between H2O (20 mL) and EtOAc (20 mL)
  3. extractionthe aqueous layer was extracted with EtOAc (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 (2:1 CHCl3/EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-3a1cfc3f7c014aca91626e107df2a6e1
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08835430B2

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