Sodium Carbonate → 1-[1-(2-Methoxyethyl)-3-piperidyl]-3-(4-phenoxyphenyl)-1h-pyrazolo[3,4-d]pyrimidin-4-amine acetate

HRID 897856Notes

Reaction equation

HRID 897856 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH:12]2[CH2:17][CH2:16][CH2:15][N:14]([CH2:18][CH2:19][O:20][CH3:21])[CH2:13]2)[N:3]=1.[O:22]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:19]([OH:20])(=[O:22])[CH3:18].[CH3:21][O:20][CH2:19][CH2:18][N:14]1[CH2:15][CH2:16][CH2:17][CH:12]([N:4]2[C:5]3=[N:6][CH:7]=[N:8][C:9]([NH2:11])=[C:10]3[C:2]([C:32]3[CH:33]=[CH:34][C:29]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:30][CH:31]=3)=[N:3]2)[CH2:13]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343774-Phenoxyphenylboronic acidHCID 223468103-iodo-1-[1-(2-methoxyethyl)-3-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 223470271-[1-(2-Methoxyethyl)-3-piperidyl]-3-(4-phenoxyphenyl)-1h-pyrazolo[3,4-d]pyrimidin-4-amine acetateYield 116.7%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of racemic 3-iodo-1-[1-(2-methoxyethyl)-3-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.050 g, 0.00012 mol) in dimethoxyethane (2.5 mL) and water (5 mL) was treated with 4-phenoxyphenylboronic acid (0.029 g, 0.00014 mol), sodium carbonate (0.033 g, 0.00031 mol) and tetrakis(triphenylphosphine) palladium (0) (0.014 g, 0.00001 mol) at 80° C. for 20 hours. The organic solvent was removed in vacuo, and the crude material was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 A, 25 cm; 30% isocratic for five minutes, then 30%-60% acetonitrile-0.1M ammonium acetate over 15 min, 21 ml/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyopholyzed to give 1-[1-(2-methoxyethyl)-3-piperidyl]-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine acetate as a white solid (0.038 g, 0.00007 mol).

Workup

  1. customThe organic solvent was removed in vacuo
  2. customthe crude material was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 A, 25 cm
  3. wait30%-60% acetonitrile-0.1M ammonium acetate over 15 min
  4. customThe acetonitrile was removed in vacuo

Sources & evidence

ORD record
ord-d4a60952671e4d2db402e30d2b08e290
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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