Reaction Steps
To a solution of (1S,2R)-4′-(4-chlorophenyl)-2-(methoxymethyl)-2′,3′,9′-trimethylspiro[cyclopropane-1,6′-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine] (2.35 g, 5.69 mmol) in DCM (70 mL) at −78° C. was added a solution of boron tribromide (1M in DCM) (Compound 202; 17.07 mmol). The reaction was warmed to rt for 30 min before MeOH was added followed by sat. aq. NaHCO3. The product was extracted with DCM (repeated 4 times), dried over a cotton plug and concentrated to dryness under vacuum. The residue was purified by flash chromatography (MeOH/DCM 0.5:99.5 to 5:95) to give ((1S,2R)-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)methanol (Compound 203) (1.9 g) as a white solid and (1S,2R)-2-(bromomethyl)-4′-(4-chlorophenyl)-2′,3′,9′-trimethylspiro[cyclopropane-1,6′-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine] (Compound 237) (449 mg) as a side product. LRMS (M+H)+: 399 m/z. 1H NMR (two conformers detected in ˜1:1 ratio) (400 MHz, DMSO-d6) δ 7.41-7.53 (m, 4H), 4.64 (t, J=5.72 Hz, 0.5H), 4.51 (t, J=5.38 Hz, 0.5H), 3.95 (quin, J=6.20 Hz, 0.5H), 3.69 (quin, J=6.20 Hz, 0.5H), 3.10-3.18 (m, 0.5H), 3.01-3.09 (m, 0.5H), 2.60 (s, 3H), 2.39 (s, 1.5H), 2.38 (s, 1.5H), 2.14-2.23 (m, 0.5H), 1.96-2.04 (m, 0.5H), 1.57 (s, 1.5H), 1.55 (s, 1.5H), 1.32-1.37 (m, 0.5H), 1.25-1.32 (m, 0.5H), 0.96 (dd, J=5.26, 9.16 Hz, 0.5H), 0.58 (t, J=6.20 Hz, 0.5H).
