Acetic Anhydride → N-(((1S,2S)-4'-(4-Chlorophenyl)-2',3',9'-trimethylspiro [cyclopropane-1,6'-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin]-2-yl)methyl)acetamide

Participants

Reaction Conditions

Reaction Steps

To a solution of ((1S,2S)-4′-(4-chlorophenyl)-2′,3′,9′-trimethylspiro[cyclopropane-1,6′-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine]-2-yl)methanamine (Compound 206; 50 mg, 0.126 mmol) in DCM (2 mL) was added N,N-diisopropylethylamine (43.9 μl, 0.251 mmol). Once the reaction was cooled to 0° C., a solution of acetic anhydride in DCM (140 mg/mL) (14.23 μl, 0.151 mmol) was added. The reaction was stirred at 0° C. for 15 min before an aqueous solution of NaHCO3(sat.) was added for the quench. The product was extracted with DCM (repeated 4 times). The organic layers were combined, dried over Na2SO4 and concentrated to dryness. The residue was purified by flash chromatography (DCM/MeOH 10:0 to 9:1) to give the desired product as an off-white solid (33 mg). LRMS (M+H)+: 440 m/z. 1H NMR (two conformers detected in ˜1:1 ratio) (400 MHz, DMSO-d6) δ 8.08 (t, J=5.15 Hz, 0.5H), 7.75 (t, J=4.92 Hz, 0.5H), 7.44-7.56 (m, 4H), 3.45-3.51 (m, 1H), 2.78-2.86 (m, 0.5H), 2.64-2.72 (m, 0.5H), 2.56-2.63 (m, 3H), 2.35-2.42 (m, 3H), 2.13-2.22 (m, 0.5H), 2.00 (dd, J=5.04, 8.93 Hz, 0.5H), 1.86 (s, 1.5H), 1.71 (s, 1.5), 1.58 (m, 1.5H), 1.57 (m, 1.5H), 1.22-1.37 (m, 1H), 0.99 (dd, J=5.26, 9.16 Hz, 0.5H), 0.58 (t, J=5.95 Hz, 0.5H).

Provenance & Evidence