Hydrochloric Acid → 4-Oxo-3-(2-oxobutyl)-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide

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Reaction Steps

1,8-Diazabicycloundec-7-ene (DBU) (150 μL, 1.00 mmol, 1.4 eq.) was added dropwise to a suspension of the hydroxymethyl derivative of temozolomide (150 mg, 0.71 mmol) and 1-bromo-2-butanone (90%, stabilized with CaCO3) (330 μL, 2.91 mmol, 4.1 eq.) in acetonitrile (4 mL). The resulting green suspension became homogeneous and was stirred overnight. The reaction was acidified with 1 N HCl and the yellow solution was extracted four times with ethyl acetate. The combined organic extracts were washed with water and then dried over MgSO4. The solvent was removed under vacuum and the pale yellow solid was triturated with diethyl ether to remove the excess of 1-bromo-2-butanone. The precipitate was filtered and washed with diethyl ether and 59 mg of a pale yellow/green solid were obtained (33% crude). LCMS: crude product (99.5% pure); m/z: 523.4 (2M+Na)+, 273.2 (M+Na)+, 251.3 ((MH+)+, 100). 1H NMR (d6 DMSO): 8.90 (s, 1H), 7.90 (s, 1H), 7.75 (s, 1H), 5.37 (s, 2H), 2.67-2.72 (q, 2H, J=7.2 Hz), 0.99-1.03 (t, 3H, J=7.2 Hz).

Provenance & Evidence