4.1.2.2.2. 1,4-Diazabicyclo[3.2.2]nonan-4-yl(furan-2-yl)methanone fumarate (13). The title
compound was prepared according to the general procedure from 16 (180 mg, 0.90 mmol, 1
equiv), Cs2CO3 (1.47 g, 4.50 mmol, 5 equiv), and carbonyl chloride 67 (148 mg, 1.1 mmol, 0.11
mL, 1.2 equiv). After standard workup and subsequent reaction with fumaric acid (65 mg, 0.56
mmol, 1 equiv), the crude salt was recrystallized from MeOH/Et2O (4:1) to provide the pure
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fumarate salt 13 × C4H4O4 as a white solid (100 mg, 53% yield); mp = 180−182 °C. H NMR
(300 MHz, CD3OD): δ 7.72 (dd, J = 1.7, 0.7 Hz, 1H), 7.11 (d, J = 3.4 Hz, 1H), 6.69 (s, 2H), 6.62
(dd, J = 3.5, 1.8 Hz, 1H), 4.87–4.80 (m, 1H), 4.23 (s, br 2H), 3.52 (dt, J = 15.9, 6.8 Hz, 6H),
2.42–2.10 (m, 4H). 13C NMR (75 MHz, CD3OD): δ 171.27 (2C), 161.01, 148.34, 146.35, 136.10
(2C), 118.38, 112.63, 56.36, 46.96, 24.28. UPLC tR = 0.87 min; HRMS (ESI) m/z calcd for
C12H17N2O2 221.1290 [M + H]+, found 221.1288.
4.1.2.2.3. 1-(1,4-Diazabicyclo[3.2.2]nonan-4-yl)ethanone fumarate (14). The title compound
was prepared according to the general procedure from 16 (150 mg, 0.75 mmol, 1 equiv), Cs2CO3
(1.20 g, 3.80 mmol, 5 equiv), and carbonyl chloride 68 (200 mg, 1.50 mmol, 0.06 mL, 1.2
equiv). After standard workup and subsequent reaction with fumaric acid (54 mg, 0.46 mmol, 1
equiv), the crude salt was recrystallized from EtOH/Et2O (4:1) to provide the pure fumarate salt
14 × 0.75 C4H4O4 as a light brown solid (150 mg, 64% yield); mp = 169−170 °C. 1H NMR (300
MHz, CD3OD): δ 6.68 (s, 1.5H), 4.80–4.71 (m, 0.5H), 4.46–4.37 (m, 0.5H), 4.06–3.97 (m, 1H),
3.96–3.87 (m, 1H), 3.52–3.37 (m, 6H), 2.20–2.10 (m, 4H), 2.15 (s, 3H). 13C NMR (75 MHz,
CD3OD): δ 171.86, 171.62 (2C), 136.21 (2C), 56.83, 55.90, 47.08, 46.82, 46.26, 30.67, 23.65,
22.03. HRMS (ESI) m/z calcd for C9H17N2O 169.1341 [M + H]+, found 169.1341.
4.1.2.3. 4-Ethyl-1,4-diazabicyclo[3.2.2]nonane fumarate (15)
To a suspension of 14 (300 mg, 1.78 mmol, 1 equiv) in anhydrous Et2O (14 mL) was added
dropwise a suspension of LiAlH4 (152 mg, 4 mmol, 2.25 equiv) in anhydrous Et2O (4 mL) at 0
°C under inert and anhydrous atmosphere. After refluxing for 3 h, the reaction was quenched
with sodium sulfate decahydrate at 0 °C, the mixture was filtered, and the filtrate was
concentrated under vacuum. The resulting residue compound 15 as free base (1 equiv) was
reacted with fumaric acid (206 mg, 1.78 mmol, 1 equiv) at rt overnight. After evaporation of the
solvent under reduced pressure, the crude salt was recrystallized from MeOH/Et2O (4:1) to
provide the pure fumarate salt 15 × 2 C4H4O4 as a white solid (165 mg, 25% yield); mp =
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134−135 °C. H NMR (300 MHz, CD3OD): δ 6.71 (s, 4H), 3.74–3.65 (m, 1H), 3.52–3.44 (m,
2H), 3.37–3.22 (m, 6H), 3.10 (q, J = 7.2 Hz, 2H), 2.44–2.28 (m, 2H), 2.19–2.01 (m, 2H), 1.29 (t,
J = 7.2 Hz, 3H). 13C NMR (75 MHz, CD3OD): δ 170.22 (2C), 135.82 (2C), 55.75, 52.30, 52.22,
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