4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyridiniumolate → 3-(4-phenoxyphenyl)-1-(4-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 2056161Notes

Reaction equation

HRID 2056161 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:24]3[CH:29]=[CH:28][N+:27]([O-])=[CH:26][CH:25]=3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)[C:3]=12.O.[PH2]([O-])=O.[Na+]>[Pd].C(O)(=O)C>[O:17]([C:14]1[CH:13]=[CH:12][C:11]([C:10]2[C:3]3[C:4](=[N:5][CH:6]=[N:7][C:2]=3[NH2:1])[N:8]([C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)[N:9]=2)=[CH:16][CH:15]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 2

HCID 223472784-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyridiniumolateHCID 178418950HCID 178418950, compound2×

Product 1

HCID 223472473-(4-phenoxyphenyl)-1-(4-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 20%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst3×HCID 176Acetic AcidSolvent

Procedure

A suspension of 4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyridiniumolate (0.100 g, 0.00025 mol) and 10% palladium on carbon (0.016 g, 0.00002 mol) in acetic acid (3 mL) was reacted with sodium hypophosphite monohydrate (0.033 g, 0.00038 mol) at 60° C. After 2 hours, an additional 10% palladium on carbon (0.016 g, 0.00002 mol) was added. The mixture was stirred 18 hours after which time additional 10% palladium on carbon (0.016 g, 0.00002 mol) and sodium hypophosphite monohydrate (0.033 g, 0.00038 mol) was added. The mixture was stirred for an additional 24 hours. The mixture was filtered through Celite® 521, washing with acetic acid. The solvent was removed in vacuo, and the residue was purified by preparative RP-HPLC (Rainin C18, 8 mm, 300 Å, 25 cm; 40% isocratic for five minutes, then 40%-100% acetonitrile—0.1M ammonium acetate over 30 min, 21 mL/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyopholyzed to give 3-(4-phenoxyphenyl)-1-(4-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.020 g, 0.00005 mol) as a white solid:

Workup

  1. additionwas added
  2. filtrationThe mixture was filtered through Celite® 521
  3. washwashing with acetic acid
  4. customThe solvent was removed in vacuo
  5. customthe residue was purified by preparative RP-HPLC (Rainin C18, 8 mm, 300 Å, 25 cm
  6. wait40% isocratic for five minutes
  7. wait40%-100% acetonitrile—0.1M ammonium acetate over 30 min
  8. customThe acetonitrile was removed in vacuo

Sources & evidence

ORD record
ord-e6a4dab063ba442da0fc71b130384bab
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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