Reaction #519322

Reaction equation

3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Triphenylphosphine

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

Intermediate M

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

diethyl azodicarboxylate

Compound 15

3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

→

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

Solvents

tetrahydrofuran

Conditions

Workup

1. 1
   TemperatureThe reaction mixture was cooled in an ice-water bath
2. 2
   Other10 minutes
3. 3
   Othersolvent was removed
4. 4
   WashThe organic layer was washed
5. 5
   Otherdried
6. 6
   Otherevaporated
7. 7
   OtherThe crude product was purified via Biotage flash column chromatography

Procedure

3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Compound 15) (3.36 g, 11.1 mmol, 1,4-dioxaspiro[4.5]decan-8-ol (Intermediate M) (5.26 g, 33.3 mmol), Triphenylphosphine (5.81 g, 22.2 mmol) were suspended in 130 ml of tetrahydrofuran. The reaction mixture was cooled in an ice-water bath and diethyl azodicarboxylate (3.9 ml, 22.2 mmol) was added dropwise. 10 minutes later, the reaction mixture was allowed to warm up to room temperature. After stirring for 2 hours, solvent was removed and the residue was taking into ethyl acetate. The organic layer was washed, dried and evaporated. The crude product was purified via Biotage flash column chromatography using dichloromethane/ethyl acetate (from 50:50 to 10:90) as the mobile phase to yield 3.829 g of 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine. 1H NMR (CDCl3) 1.83 (m, 2H), 1.945 (m, 2H), 2.05 (m, 2H), 2.45 (m, 2H), 3.99 (s, 4H), 4.86 (m, 1H), 5.74 (bs, 2H), 7.09 (m, 2H), 7.15 (m, 3H), 7.39 (m, 2H), 7.66 (d, J=8.70 Hz, 2H), 8.37 (s, 1H); LC/MS (MH+32 444).

Source