Cyclobutanecarbonyl chloride → N-((5-Oxo-4,5-dihydro-1,2,4-triazin-6-yl)methyl)cyclobutanecarboxamide

HRID 2042279Notes

Reaction equation

HRID 2042279 reaction equation
[NH2:1][CH2:2][C:3]1[C:4](=[O:9])[NH:5][CH:6]=[N:7][N:8]=1.C(N(CC)C(C)C)(C)C.[CH:19]1([C:23](Cl)=[O:24])[CH2:22][CH2:21][CH2:20]1>CN(C)C=O.N1C=CC=CC=1>[O:9]=[C:4]1[C:3]([CH2:2][NH:1][C:23]([CH:19]2[CH2:22][CH2:21][CH2:20]2)=[O:24])=[N:8][N:7]=[CH:6][NH:5]1

Participants

6

Reactant 3

HCID 78705Cyclobutanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 1357424956-(Aminomethyl)-1,2,4-triazin-5(4H)-one

Product 1

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

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-aminomethyl-4H-[1,2,4]triazin-5-one (500 mg, 3.96 mmol) and N,N-diisopropylethylamine (DIEA) (0.829 mL, 4.76 mmol) in anhydrous N,N-dimethylforamide (DMF) (20 mL) and anhydrous pyridine (2 mL) was dropwise charged with cyclobutanecarbonyl chloride (0.451 mL, 3.96 mmol) at 0° C. then warmed to rt and stirred for an additional 1.5 h. The reaction mixture was quenched with H2O (2 mL) and concentrated in vacuo and was purified by chromatography on silica gel [eluting with 5% MeOH in DCM (200 mL)→10% MeOH in DCM (800 mL)], affording the title compound; 1H NMR (DMSO-d6, 400 MHz) δ 1.7-1.82 (m, 1H), 1.70-1.92 (m, 1H); 1.97-2.07 (m, 2H); 2.07-2.19 (m, 2H); 3.55-3.67 (m, 1H); 4.19 (d, 2H); 7.97 (brt, J=5.6 Hz, 1H); 8.67 (s, 1H); MS (ES+): m/z 209.25 (100) [MH+], HPLC: tR=1.56 min (MicromassZQ, polar—5 min).

Workup

  1. customThe reaction mixture was quenched with H2O (2 mL)
  2. concentrationconcentrated in vacuo
  3. customwas purified by chromatography on silica gel [eluting with 5% MeOH in DCM (200 mL)→10% MeOH in DCM (800 mL)]

Sources & evidence

ORD record
ord-321910d6cee940918ef0c07b2cc135d0
Source dataset
uspto-grants-2013_11
Patent number
US08586546B2

Reaction notes

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