Hydrochloric Acid → tert-Butyl 3-[9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-methyl-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]azetidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-methyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (100 mg, 0.2 mmol) was treated with 4 N HCl in dioxane (1 mL), and then the solvent was evaporated. The residue was stirred in methanol (5 mL) and tert-butyl 3-oxoazetidine-1-carboxylate (140 mg, 0.84 mmol) was added. Sodium cyanoborohydride (120 mg, 1.9 mmol) was added and the mixture was warmed to 60° C. for 1.5 hours. Purification by preparative LCMS (pH 10) gave the desired compound (3.3 mg, 10%). LCMS calculated for C26H35ClN7O3 (M+H)+: m/z=528.2; found: 528.3. 1H NMR (300 MHz, CD3OD): δ 8.14 (s, 1 H), 7.33 (s, 1 H), 6.33 (m, 1 H), 4.00 (m, 2 H), 3.82 (m, 1 H), 3.74 (m, 2 H), 3.63 (m, 3 H), 3.41 (m, 1 H), 2.76 (m, 2 H), 2.58 (s, 3 H), 2.37 (s, 3 H), 1.79 (m, 3 H), 1.42 (s, 9H).

Provenance & Evidence