Reaction #519347

Reaction equation

2-phenoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine

1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine

Intermediate N

1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine

sodium carbonate

acetonitrile

→

1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-(6-phenoxy-3-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Yield 71.9%

Solvents

ethylene glycol dimethyl ether

water

diethyl ether

Conditions

Workup

1. 1
   Otherethylene glycol dimethyl ether was removed under reduced pressure
2. 2
   FiltrationThe precipitate was collected by filtration
3. 3
   Washwashed with water once

Procedure

A mixture of 2-phenoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (Intermediate AG) (1.1 g, 0.0037 mol), 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate N) (1.29 g, 0.0032 mol), tetrakis(triphenylphosphine)palladium (0.22 g, 0.00019 mol) and sodium carbonate (0.85 g, 0.008 mol) was heated in a mixture of ethylene glycol dimethyl ether (40 mL) and water (20 mL) at 80° C. for 16 hours under an atmosphere of nitrogen. The mixture was allowed to cool to ambient temperature and ethylene glycol dimethyl ether was removed under reduced pressure. The precipitate was collected by filtration, washed with water once, acetonitrile twice and diethyl ether twice to give 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-(6-phenoxy-3-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine as an off-white solid (1.03 g, 0.0023 mol): 1H NMR (DMSO-d6, 400 MHz) 8.36 (s, 1H), 8.24 (s, 1H), 8.03 (d, 1H), 7.45 (t, 2H), 7.22 (m, 3H), 7.16 (d, 1H), 4.81 (m, 1H), 3.93 (s, 4H), 2.24 (m, 2H), 1.88 (m, 6H); MS: MH+445.

Source