Triphenylphosphine → Tert-butyl 2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidine-1-carboxylate

HRID 1778434Notes

Reaction equation

HRID 1778434 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:5]=[CH:4][C:3]=1[C:15]1[C:23]2[C:18](=[N:19][CH:20]=[N:21][C:22]=2[NH2:24])[NH:17][N:16]=1.O[CH2:26][CH:27]1[CH2:30][CH2:29][N:28]1[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[NH2:24][C:22]1[N:21]=[CH:20][N:19]=[C:18]2[N:17]([CH2:26][CH:27]3[CH2:30][CH2:29][N:28]3[C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[N:16]=[C:15]([C:3]3[CH:4]=[CH:5][C:6]([O:8][C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=4)=[CH:7][C:2]=3[F:1])[C:23]=12

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 14821739tert-Butyl 2-(hydroxymethyl)azetidine-1-carboxylateHCID 1785087183-(2-Fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 90001120Tert-butyl 2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidine-1-carboxylateYield 175.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 3-(2-fluoro-4-phenoxy-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (300 mg, 0.930 mmol), tert-butyl 2-(hydroxymethyl)azetidine-1-carboxylate (0.33 mL, 1.9 mmol) and PPh3 (733.86 mg, 2.8 mmol) in THF (10 mL) in ice bath, the DIAD (0.37 mL, 1.87 mmol) as a solution in 5 ml THF was slowly added. The mixture was stirred at RT overnight and then the solvent was removed. To the residue was added H2O and the mixture was extracted with EtOAc. The combined organic layer was washed with NaHCO3, then brine, and dried over Na2SO4. The solvent was removed to get tert-butyl 2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidine-1-carboxylate weighing 800 mg, which was used without further purification for the next step.

Workup

  1. customthe solvent was removed
  2. additionTo the residue was added H2O
  3. extractionthe mixture was extracted with EtOAc
  4. washThe combined organic layer was washed with NaHCO3
  5. dry with materialbrine, and dried over Na2SO4
  6. customThe solvent was removed

Sources & evidence

ORD record
ord-a338352a78564d6181cf7a80c617799b
Source dataset
uspto-grants-2016_02
Patent number
US09266895B2

Reaction notes

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