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 422644노트

반응식

HRID 422644 반응식
[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

참가 물질

3

반응물 1

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

생성물 1

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

시약·촉매·용매 1

HCID 24813Phosphorus oxychloride용매

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온도
0 °C

실험 절차

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 ispropanol (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-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).

후처리

  1. temperatureThe reaction was heated for 2 h
  2. concentrationthen concentrated in vacuo
  3. customquenched with 2 M NH3 in ispropanol (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]

출처 및 근거

ORD 기록
ord-9874e7ab19eb4150baa40657fb727468
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101613B2

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