Reaction #519326

Reaction equation

1,4-dioxaspiro[4.5]decan-8-ol

Intermediate M

1,4-dioxaspiro[4.5]decan-8-ol

triphenylphosphine

3-Iodo-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine

diethyl azodicarboxylate

→

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

Yield 54.8%

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   Temperatureto warm to room temperature for 1 hour
2. 2
   ConcentrationThe reaction mixture was concentrated under reduced pressure
3. 3
   workup.DISSOLUTIONThe residue was dissolved in ethyl acetate (300-400 mL)
4. 4
   workup.WAITto stand overnight
5. 5
   OtherA precipitate formed which
6. 6
   Filtrationwas collected by filtration
7. 7
   Washwashed with ethyl acetate
8. 8
   Otherdried on the lyophilizer

Procedure

3-Iodo-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine (Intermediate LA) (11 g, 0.042 mol) was suspended in tetrahydrofuran (500 mL) at room temperature under a nitrogen atmosphere. A solution of 1,4-dioxaspiro[4.5]decan-8-ol (Intermediate M) (19.98 g, 0.126 mol) in tetrahydrofuran (50 mL) and subsequently triphenylphosphine (22.1 g, 0.084 mol ) was added to the suspension. The suspension was cooled to 0° C. and then diethyl azodicarboxylate (14.67 g, 0.084 mol) was added slowly. After stirring the reaction mixture at 0° C. for 15 min, it was allowed to warm to room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (300-400 mL) and allowed to stand overnight. A precipitate formed which was collected by filtration, washed with ethyl acetate, and dried on the lyophilizer to give 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine as a pale yellow solid (54%, 9.12 g, 0.023 mol): 1H NMR (DMSO-d6, 400 MHz) 8.19 (s, 1H), 4.70 (m, 1H), 3.90 (m, 4H), 2.13 (m, 2H), 1.74 (m, 6H). TLC (dichloromethane/methanol=9:1) Rf 0.61.

Source