N-((5-Oxo-4,5-dihydro-1,2,4-triazin-6-yl)methyl)cyclobutanecarboxamide → 7-cyclobutyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

HRID 17977ノート

反応式

HRID 17977 の反応式
[O:1]=[C:2]1[C:7]([CH2:8][NH:9][C:10]([CH:12]2[CH2:15][CH2:14][CH2:13]2)=O)=[N:6][N:5]=[CH:4][NH:3]1>P(Cl)(Cl)(Cl)=O>[CH:12]1([C:10]2[N:6]3[C:7]([C:2](=[O:1])[NH:3][CH:4]=[N:5]3)=[CH:8][N:9]=2)[CH2:15][CH2:14][CH2:13]1

参加物

3

反応物 1

HCID 135993273N-((5-Oxo-4,5-dihydro-1,2,4-triazin-6-yl)methyl)cyclobutanecarboxamide

生成物 1

HCID 1359932727-cyclobutyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

試薬・触媒・溶媒 1

HCID 24813Phosphorus oxychloride溶媒

反応条件

温度
0 °C

実験手順

A solution of cyclobutanecarboxylic acid (5-oxo-4,5-dihydro-[1,2,4]triazin-6-ylmethyl)-amide (1.33 g, 6.39 mmol) in phosphorus oxychloride (POCl3) (10 mL) was heated to 55° C. The reaction was heated for 2 h then concentrated in vacuo and the crude oil was cooled to 0° C. in an ice-bath and quenched with 2 M NH3 in ispropanol (i-PrOH) until slightly basic. This crude reaction mixture was concentrated in vacuo and was partitioned between CH2Cl2 and H2O and separated. The aqueous layer was extracted with CH2Cl2 (3×) and the combined organic fractions were dried over sodium sulfate (Na2SO4), filtered and concentrated in vacuo. The crude material was purified by chromatography on silica gel [eluting with 5% MeOH in CH2Cl2], resulting in the title compound as an off-white solid; 1H NMR (DMSO-d6, 400 MHz) δ 1.86-1.96 (m, 1H), 2.00-2.13 (m, 1H); 2.26-2.46 (m, 4H); 3.87-4.00 (m, 1H); 7.71 (s, 1H); 7.87 (d, J=3.6 Hz, 1H); 11.7 (brs, 1H); MS (ES+): m/z 191.27 (100) [MH+], HPLC: tR=2.06 min (MicromassZQ, polar—5 min).

後処理

  1. temperatureThe reaction was heated for 2 h
  2. concentrationthen concentrated in vacuo
  3. customquenched with 2 M NH3 in ispropanol (i-PrOH) until slightly basic
  4. customThis crude reaction mixture
  5. concentrationwas concentrated in vacuo
  6. customwas partitioned between CH2Cl2 and H2O
  7. customseparated
  8. extractionThe aqueous layer was extracted with CH2Cl2 (3×)
  9. dry with materialthe combined organic fractions were dried over sodium sulfate (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude material was purified by chromatography on silica gel [eluting with 5% MeOH in CH2Cl2]

出典と根拠

ORDレコード
ord-0930e77554c04451a327d99ee69a90a7
出典データセット
uspto-grants-2010_06
特許番号
US07741324B2

反応ノート

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