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

HRID 432140Notes

Reaction equation

HRID 432140 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[N:20][C:21]=3[NH2:23])[NH:16][N:15]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:24]1[C:28]2([CH2:33][CH2:32][CH:31](O)[CH2:30][CH2:29]2)[O:27][CH2:26][CH2:25]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[O:24]1[C:28]2([CH2:33][CH2:32][CH:31]([N:16]3[C:17]4=[N:18][CH:19]=[N:20][C:21]([NH2:23])=[C:22]4[C:14]([C:11]4[CH:12]=[CH:13][C:8]([O:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)=[CH:9][CH:10]=4)=[N:15]3)[CH2:30][CH2:29]2)[O:27][CH2:26][CH2:25]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 5673521,4-Dioxaspiro(4.5)decan-8-ol2×HCID 178508717HCID 178508717, compound2×

Product 1

HCID 223467671-(1,4-dioxaspiro[4.5]dec-8-yl)-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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).

Workup

  1. temperatureThe reaction mixture was cooled in an ice-water bath
  2. custom10 minutes
  3. customsolvent was removed
  4. washThe organic layer was washed
  5. customdried
  6. customevaporated
  7. customThe crude product was purified via Biotage flash column chromatography

Sources & evidence

ORD record
ord-7dba250cc96f4c1db3089b569e373a93
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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