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

HRID 1876191노트

반응식

HRID 1876191 반응식
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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 702Ethanol용매

반응 조건

온도
60 °C

실험 절차

(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.

후처리

  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

출처 및 근거

ORD 기록
ord-387299232aad4dd3a9a1a7924292f7c2
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08309562B2

반응 노트

불러오는 중…