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 17977Notes

Reaction equation

HRID 17977 reaction equation
[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

Participants

3

Reactant 1

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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]

Sources & evidence

ORD record
ord-0930e77554c04451a327d99ee69a90a7
Source dataset
uspto-grants-2010_06
Patent number
US07741324B2

Reaction notes

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