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

HRID 1876191ノート

反応式

HRID 1876191 の反応式
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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
60 °C

実験手順

(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.

後処理

  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

出典と根拠

ORDレコード
ord-387299232aad4dd3a9a1a7924292f7c2
出典データセット
uspto-grants-2012_11
特許番号
US08309562B2

反応ノート

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