Synthesis of Pyrazolo-pyridine Spiro Piperidine

Example 164

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Step 1.

5-(7-Methylpyrazolo[1,5-a]pyridin-6-yl)spiro[3H-benzofuran-2,4′-piperidine] 2HCl was synthesized using tert-butyl 5-(7-methylpyrazolo[1,5-a]pyridin-6-yl)spiro[3H-benzofuran-2,4′-piperidine]-1′-carboxylate and 4 M HCl in dioxane. Analysis: LCMS m/z=320 (M+1); ¹H NMR (400 MHz, DMSO-d₆) δ: 8.94 (dd, J=4.0, 1.8 Hz, 1H), 8.38 (dd, J=8.3, 1.8 Hz, 1H), 7.75 (d, J=8.8 Hz, 1H), 7.57 (d, J=8.5 Hz, 1H), 7.55-7.52 (m, 1H), 7.47 (d, J=1.5 Hz, 1H), 7.38 (dd, J=8.3, 2.0 Hz, 1H), 6.88 (d, J=8.3 Hz, 1H), 6.01 (s, 2H), 3.91 (s, 3H), 3.57-3.39 (m, 4H), 3.12 (s, 2H), 1.86-1.67 (m, 4H).

Step 2.

5-(7-Methylpyrazolo[1,5-a]pyridin-6-yl)spiro[3H-benzofuran-2,4′-piperidine]-1′-carboxamide was synthesized using 5-(7-methylpyrazolo[1,5-a]pyridin-6-yl)spiro[3H-benzofuran-2,4′-piperidine] 2HCl and trimethylsilyl isocyanate. Analysis: LCMS m/z=363 (M+1); ¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (d, J=2.3 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.27 (d, J=1.5 Hz, 1H), 7.16 (d, J=8.8 Hz, 2H), 6.86 (d, J=8.3 Hz, 1H), 6.68 (d, J=2.3 Hz, 1H), 6.01 (s, 2H), 3.53-3.37 (m, 4H), 3.10 (s, 2H), 2.65 (s, 3H), 1.83-1.67 (m, 4H).