N-(3-Aminopropyl)morpholine → N2-(3-chlorophenyl)-N4-(3-morpholin-4-yl-propyl)-pyrimidine-2,4-diamine

HRID 1803914Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1803914
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=2)[N:3]=1.C(N(C(C)C)CC)(C)C.[O:25]1[CH2:30][CH2:29][N:28]([CH2:31][CH2:32][CH2:33][NH2:34])[CH2:27][CH2:26]1>C1COCC1>[Cl:15][C:11]1[CH:10]=[C:9]([NH:8][C:4]2[N:3]=[C:2]([NH:34][CH2:33][CH2:32][CH2:31][N:28]3[CH2:29][CH2:30][O:25][CH2:26][CH2:27]3)[CH:7]=[CH:6][N:5]=2)[CH:14]=[CH:13][CH:12]=1

Komponenten

5

Edukt 3

HCID 61055N-(3-Aminopropyl)morpholine2×HCID 81531DiisopropylethylamineHCID 590282434-chloro-N-(3-chlorophenyl)pyrimidin-2-amine

Produkt 1

HCID 24797260N2-(3-chlorophenyl)-N4-(3-morpholin-4-yl-propyl)-pyrimidine-2,4-diamineAusbeute 41 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To 4-chloro-N-(3-chlorophenyl)pyrimidin-2-amine, 3, (0.2 g, 0.84 mmol) in THF (4 mL) is added diisopropylethylamine (0.29 mL, 1.67 mmol) followed by 3-morpholino-propylamine (0.245 mL, 1.67 mmol). The resulting mixture was heated to reflux for 6 hours. Another 2 equivalents of 3-morpholinopropylamine (0.245 mL, 1.67 mmol) is added and the reaction heated to reflux and stirred for 18 hours. The resulting mixture is heated to reflux for 18 hours. The reaction is cooled to room temperature and concentrated in vacuo. The residue is diluted with 5 mL water and extracted with EtOAc (3×25 mL). The combined organic layers are dried (MgSO4) and concentrated in vacuo. The residue is diluted with 5 mL water and extracted with EtOAc (3×25 mL). The combined organic layers are dried (MgSO4) and concentrated in vacuo. This residue is purified over silica (6% MeOH in CH2Cl2 with 0.7% Et3N) to afford 0.120 g (41% yield) of the desired compound. 1H NMR (DMSO-d6, 300 MHz): δ 1.68-1.75 (m, 2H), 2.34-2.40 (m, 6H), 3.30-3.35 (m, 2H), 3.55-3.58 (m, 4H), 5.97 (d, J=5.7 Hz, 1H), 6.88 (d, J=7.2 Hz, 1H), 7.19-7.28 (m, 2H), 7.59 (d, J=7.2 Hz, 1H), 7.80 (br s, 1H), 8.13 (br s, 1H), 9.19 (br s, 1H). MS (ESI, pos. ion) m/z: 348 (M+1).

Aufarbeitung

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 6 hours
  3. temperaturethe reaction heated
  4. temperatureto reflux
  5. temperatureThe resulting mixture is heated
  6. temperatureto reflux for 18 hours
  7. concentrationconcentrated in vacuo
  8. additionThe residue is diluted with 5 mL water
  9. extractionextracted with EtOAc (3×25 mL)
  10. dry with materialThe combined organic layers are dried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. additionThe residue is diluted with 5 mL water
  13. extractionextracted with EtOAc (3×25 mL)
  14. dry with materialThe combined organic layers are dried (MgSO4)
  15. concentrationconcentrated in vacuo
  16. customThis residue is purified over silica (6% MeOH in CH2Cl2 with 0.7% Et3N)

Quellen und Nachweise

ORD-Eintrag
ord-b223c7707a8c44b197b082d7901018ea
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354407B2

Notizen zur Reaktion

Wird geladen…