Hydrochloric Acid → N-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-acetamide

HRID 1876191Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1876191
NCC1N=C(N(C2C=CC(OC)=CC=2)C)C2C(=CC=CC=2)N=1.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]([CH3:54])[C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[N:35]=[C:34]([CH2:42][N:43]3C(=O)C4[C:45](=CC=CC=4)[C:44]3=[O:53])[N:33]=2)=[CH:27][CH:26]=1.O.NN.Cl>CCO>[CH3:23][O:24][C:25]1[CH:26]=[CH:27][C:28]([N:31]([CH3:54])[C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[N:35]=[C:34]([CH2:42][NH:43][C:44](=[O:53])[CH3:45])[N:33]=2)=[CH:29][CH:30]=1

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 24654Hydrazine hydrate (1:1)HCID 44555457(2-Aminomethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amineHCID 592372612-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-isoindole-1,3-dione

Produkt 1

HCID 59242014N-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-acetamideAusbeute 52 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

(2-Aminomethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine: A solution of 2-{4-[(4-methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-isoindole-1,3-dione (8.561 g, 20.2 mmol) in EtOH (100 mL) was treated with hydrazine mono-hydrate (3.0 mL, 61.8 mmol) and heated to 60° C. for 2 h. The reaction was cooled to rt, HCl (2 N, 50 mL) added and the reaction heated to 60° C. for 30 min. After cooling to rt the solid was filtered off. The filtrate was concentrated, basified with 5% NaOH and extracted with CH2Cl2. The organic layers were combined, dried (MgSO4), filtered and concentrated. The residue was purified by gradient reverse phase MPLC (MeCN/H2O with 0.1% TFA) and the free base re-extracted as above to yield 3.10 g (52%) of the title compound. 1H NMR (CDCl3) δ 7.76 (d, 1H), 7.54 (ddd, 1H), 7.08-7.16 (m, 2H), 6.95-7.05 (m, 2H), 6.86-6.94 (m, 2H), 4.07 (s, 2H), 3.84 (s, 3H), 3.60 (s, 3H), 2.00 (s(br), 2H); 13C NMR (CDCl3) δ 165.9, 162.0, 158.2, 152.2, 141.6, 132.0, 128.2, 127.6, 126.5, 124.4, 115.5, 115.4, 55.7, 49.1, 43.0; HRMS (ES) calcd for C17H18N4O (M+H) 295.1553, found 295.1506.

Aufarbeitung

  1. temperatureThe reaction was cooled to rt
  2. temperaturethe reaction heated to 60° C. for 30 min
  3. temperatureAfter cooling to rt the solid
  4. filtrationwas filtered off
  5. concentrationThe filtrate was concentrated
  6. extractionextracted with CH2Cl2
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by gradient reverse phase MPLC (MeCN/H2O with 0.1% TFA)
  11. extractionthe free base re-extracted as above

Quellen und Nachweise

ORD-Eintrag
ord-387299232aad4dd3a9a1a7924292f7c2
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08309562B2

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