Hydrochloric Acid → Ethyl 2-(8-carbamoyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)acetate

Participants

Reaction Steps

1,8-Diazabicycloundec-7-ene (DBU) (32 μL, 0.215 mmol, 1.5 eq.) was added dropwise to a suspension of the hydroxymethyl derivative of Temozolomide (3-(hydroxymethyl)-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide) (30 mg, 0.143 mmol) and ethyl iodoacetate (43 μL, 0.357 mmol, 2.5 eq.) in acetonitrile (700 μL). 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 ethyl iodoacetate. The precipitate was filtered to give 5 mg of the title compound as a yellow solid (13% crude). 1H NMR (DMSO d6): 8.93 (s, 1H), 7.89 (s, 1H), 7.75 (s, 1H), 5.23 (s, 2H), 4.20-4.23 (q, 2H, J=7.1 Hz), 1.22-1.26 (t, 3H, J=7.1 Hz). LCMS: 97% pure; m/z: 289.4 (M+Na+), 267.5 (MH+).

Provenance & Evidence