Reaction #965605

Reaction equation

product

(4s)-4-(6-Nitropyridin-3-yloxy)-1-azatricyclo[3.3.1.13,7]decane hydrochloride

→

title compound

(4s)-4-(6-Aminopyridin-3-yloxy)-1-azatricyclo[3.3.1.13,7]decane

Solvents

THF MeOH

Conditions

Workup

1. 1
   OtherAfter removing the catalyst
2. 2
   Filtrationby filtration
3. 3
   Otherthe product was purified by preparative HPLC [Waters® XTerra RP18 column, 5μ, 30×100 mm, flow rate 40 mL/minutes, 5-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide), with UV detection at 254 nm]
4. 4
   workup.ADDITIONFractions containing the desired compound
5. 5
   Concentrationconcentrated under vacuum
6. 6
   workup.ADDITIONdiluted with methanol
7. 7
   Filtrationfiltered

Procedure

A solution of the product of Example 16B (380 mg, 1.2 mmol) in THF-MeOH (10 mL, 1:1) was treated with Raney nickel (401 mg, 6.83 mmol) under an atmosphere of hydrogen (60 psi), and the mixture was warmed to 50° C. for 1 hour. After removing the catalyst by filtration, the product was purified by preparative HPLC [Waters® XTerra RP18 column, 5μ, 30×100 mm, flow rate 40 mL/minutes, 5-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide), with UV detection at 254 nm]. Fractions containing the desired compound were pooled, concentrated under vacuum, diluted with methanol, and filtered to afford the title compound: 1H NMR (300 MHz, methanol-D4) δ ppm 1.66 (s, 1H), 1.80 (d, J=12.5 Hz, 2H), 1.99 (s, 2H), 2.28-2.39 (m, 2H), 3.01-3.12 (m, 4H), 3.24 (ddd, J=14.1, 2.4, 2.2 Hz, 2H), 4.45 (t, J=3.2 Hz, 1H), 6.57 (dd, J=9.2, 0.7 Hz, 1H), 7.27 (dd, J=9.0, 2.9 Hz, 1H), 7.67 (dd, J=3.1, 0.7 Hz, 1H). MS (+ESI) m/z=246 (M+H)+.

Source