Reaction #519364

Reaction equation

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

2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]-pyrimidine

sodium carbonate

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-[4-(2-pyrimidinyloxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Yield 75.7%

Solvents

1,2-dimethoxyethane

water

Conditions

Workup

1. 1
   Temperatureto cool to ambient temperature
2. 2
   FiltrationThe precipitate was filtered
3. 3
   Washwashed with 1,2-dimethoxyethane
4. 4
   Otherdried in vacuo

Procedure

A mixture of 1-(1,4-dioxaspiro[4,5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate N) (1.50 g, 0.00374 mol), 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]-pyrimidine (intermediate BA) (1.23 g, 0.00412 mol), tetrakis(triphenylphosphine)palladium(0) (0.26 g, 0.00022 mol) and sodium carbonate (0.993 g, 0.00937 mol) in 40 mL 1,2-dimethoxyethane and 20 mL water was heated at 80° C. for eighteen hours, after which time additional 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.15 g, 0.00037 mol) was added. The mixture was stirred for an additional hour and then allowed to cool to ambient temperature. The precipitate was filtered and washed with 1,2-dimethoxyethane and dried in vacuo, to give 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-[4-(2-pyrimidinyloxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a white solid (1.26 g, 0.00283 mol): 1H NMR (DMSO-d6, 400 MHz) 8.68 (d, 2H), 8.254 (s, 1H), 7.73 (d, 2H), 7.37 (d, 2H), 7.31 (t, 1H), 6.30-7.20 (bs, 2H), 4.78-4.84 (m, 1H), 3.91 (s, 4H), 2.22-2.30 (m, 2H), 1.73-1.92 (m, 6H).

Source