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

HRID 1876191Notes

Reaction equation

HRID 1876191 reaction equation
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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

(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.

Workup

  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

Sources & evidence

ORD record
ord-387299232aad4dd3a9a1a7924292f7c2
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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