Trifluoroacetic acid → 2-(4-(4-(4-(2-Aminopropan-2-yl)phenyl)-5-chloropyrimidin-2-ylamino)phenyl)ethanol

HRID 1359448

Reaktionsgleichung

Reaktionsgleichung von HRID 1359448
C(OC([NH:8][C:9]([C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:23]([Cl:24])=[CH:22][N:21]=[C:20](Cl)[N:19]=2)=[CH:14][CH:13]=1)([CH3:11])[CH3:10])=O)(C)(C)C.[NH2:26][C:27]1[CH:35]=[CH:34][C:30]([CH2:31][CH2:32][OH:33])=[CH:29][CH:28]=1.FC(F)(F)C(O)=O>C(OCCO)C>[NH2:8][C:9]([C:12]1[CH:13]=[CH:14][C:15]([C:18]2[C:23]([Cl:24])=[CH:22][N:21]=[C:20]([NH:26][C:27]3[CH:35]=[CH:34][C:30]([CH2:31][CH2:32][OH:33])=[CH:29][CH:28]=3)[N:19]=2)=[CH:16][CH:17]=1)([CH3:10])[CH3:11]

Komponenten

5

Edukt 3

HCID 6422Trifluoroacetic acidHCID 669044-Aminophenethyl alcoholHCID 181832304-[4-(1-Tert-butoxycarbonylamino-1-methylethyl)phenyl]-2,5-dichloropyrimidine

Produkt 1

HCID 99080262-(4-(4-(4-(2-Aminopropan-2-yl)phenyl)-5-chloropyrimidin-2-ylamino)phenyl)ethanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8076Glycol monoethyl etherLösungsmittel

Versuchsvorschrift

A mixture of 4-[4-(1-tertbutoxycarbonylamino-1-methylethyl)phenyl]-2,5-dichloropyrimidine (1.53 g, 4.0 mmol) and 4-aminophenethyl alcohol (1.10 g, 8.0 mmol) in 2-ethoxyethanol (15 ml) was heated to reflux for 18 h. The reaction was cooled to room temperature, trifluoroacetic acid (2 ml) added and the reaction stirred for 30 min. Solvent was removed in vacuo and the residue partitioned between CH2Cl2 (100 ml) and saturated, aqueous Na2CO3 (80 ml). The aqueous layer was re-extracted with CH2Cl2 (2×80 ml) and the combined CH2Cl2 layer washed with aqueous Na2CO3 (80 ml), brine (80 ml), dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica, 10-15% methanol in CH2Cl2) to give the title compound as a buff solid (1.30 g) m.p. 162-163°. δH (d6DMSO) 9.74 (1H, s), 8.55 (1H, s), 7.76 (2H, d, J 8.5 Hz), 7.68 (2H, d, J 8.5 Hz), 7.62 (2H, d, J 8.5 Hz), 7.12 (2H, d, J 8.5 Hz), 4.57 (1H, bs), 3.55 (2H, m), 2.65 (2H, t, J 7.2 Hz), 1.41 (6H, s); MS (ESI) 383 (MH+, 35Cl, 100%).

Aufarbeitung

  1. temperaturewas heated
  2. temperatureto reflux for 18 h
  3. customSolvent was removed in vacuo
  4. customthe residue partitioned between CH2Cl2 (100 ml)
  5. extractionThe aqueous layer was re-extracted with CH2Cl2 (2×80 ml)
  6. washthe combined CH2Cl2 layer washed with aqueous Na2CO3 (80 ml), brine (80 ml)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography (silica, 10-15% methanol in CH2Cl2)

Quellen und Nachweise

ORD-Eintrag
ord-8e969767587e4fc185332acaf09ac5a9
Quelldatensatz
uspto-grants-2003_07
Patentnummer
US06600037B1

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