3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → HCID 71765515, compound

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-fluoro-2-methyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (75 mg, 0.15 mmol) was stirred in 4 N HCl in dioxane (5 mL) and evaporated. The residue was stirred in methanol (4 mL) and tert-butyl 3-oxoazetidine-1-carboxylate (110 mg, 0.61 mmol) was added. Sodium cyanoborohydride (86 mg, 1.4 mmol) was added and the mixture was warmed to 60° C. overnight and evaporated. Water was added and the mixture was extracted with ethyl acetate. The extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. The reactions were purified by prep HPLC on C-18 column eluting water:acetonitrile gradient buffered pH 10 to give two diastereomers (peak #1 and 2): Peak #1 (Example 26): LCMS calculated for C26H34ClFN7O3 (M+H)+: m/z=546.2; found: 546.2 1H NMR (300 MHz, CD3OD): δ 8.14 (s, 1 H), 7.38 (m, 1 H), 6.32 (m, 1 H), 4.11 (m, 1 H), 3.95 (m, 2 H), 3.78 (m, 2 H), 3.50 (m, 2 H), 2.92 (m, 2 H), 2.65 (m, 1 H), 2.60 (s, 3 H), 1.80 (m, 3 H), 1.42 (s, 9 H), 1.38 (m, 3 H). Peak #2 (Example 27): LCMS calculated for C26H34ClFN7O3 (M+H)+: m/z=546.2; Found: 546.2.

Provenance & Evidence