Chloroform → HCID 58087997, compound

Temperature

80 °C

To N-(2-(1H-imidazole-1-carbothioamido)benzo[d]thiazol-6-yl)acetamide (300 mg, 0.95 mmol) in N,N-dimethylformamide (10 mL) was added (S)-3-(aminomethyl)quinuclidin-3-ol, 2HCl (238 mg, 1 mmol) and triethylamine (0.39 mL, 2.84 mmol). The reaction was heated to 80° C. for 3 hours. N,N′-diisopropylcarbodiimide (0.59 mL, 3.78 mmol) was then added to the reaction mixture. The mixture was heated at 80° C. for another 2 hours. The reaction was cooled, then chloroform and water were added to the mixture. The organic layer concentrated in vacuo to yield crude product. The crude material was purified via flash chromatography (2-20% [10% ammonium hydroxide/methanol-chloroform). The product fractions were then triturated with ether to yield (R)—N-(2-(4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octane]-2-ylamino)benzo[d]thiazol-6-yl)acetamide (144.5 mg, 0.39 mmol, 41.2% yield) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.98 (1 H, s), 8.93 (1 H, br. s.), 8.12 (1 H, d, J=1.83 Hz), 7.52 (1 H, d, J=8.42 Hz), 7.38 (1 H, dd, J=8.60, 2.01 Hz), 3.88 (1 H, d, J=9.88 Hz), 3.62 (1 H, d, J=9.88 Hz), 3.02 (2 H, s), 2.74-2.85 (2 H, m), 2.66 (2 H, t, J=7.68 Hz), 2.05 (4 H, s), 1.91 (1 H, br. s.), 1.41-1.64 (3 H, m). MS (LC/MS) R.T.=1.55; [M+H]+=372.2.

1. temperatureThe mixture was heated at 80° C. for another 2 hours
2. temperatureThe reaction was cooled
3. concentrationThe organic layer concentrated in vacuo
4. customto yield crude product
5. customThe crude material was purified via flash chromatography (2-20% [10% ammonium hydroxide/methanol-chloroform)
6. customThe product fractions were then triturated with ether

ORD record

ord-f3ae0e89ace5445295d6263352129123

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07863291B2