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 244131ノート

反応式

HRID 244131 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 crude 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 isopropanol (IPA) until slightly basic. This crude reaction mixture was concentrated in vacuo and was partitioned between DCM and H2O and separated. The aqueous layer was extracted with DCM (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 DCM], resulting in the title compound as an off-white solid; 1H NMR (DMSO-d, 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 isopropanol (IPA) until slightly basic
  4. customThis crude reaction mixture
  5. concentrationwas concentrated in vacuo
  6. customwas partitioned between DCM and H2O
  7. customseparated
  8. extractionThe aqueous layer was extracted with DCM (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 DCM]

出典と根拠

ORDレコード
ord-e442d8de119744c99d786b464913c901
出典データセット
uspto-grants-2014_02
特許番号
US08653268B2

反応ノート

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