Formamidine acetate → 7-Aminopyrazolo(4,3-d)pyrimidine

HRID 1171020Notes

Reaction equation

HRID 1171020 reaction equation
[N+:1]([C:4]1[CH:5]=[N:6][NH:7][C:8]=1[C:9]#[N:10])([O-])=O.C(O)(=O)C.[CH:15](N)=[NH:16]>C(O)C.[Pd]>[NH:7]1[C:8]2[C:9]([NH2:10])=[N:16][CH:15]=[N:1][C:4]=2[CH:5]=[N:6]1

Participants

5

Reactant 2

HCID 160693Formamidine acetateHCID 3384184-nitro-1H-pyrazole-3-carbonitrile

Product 1

HCID 966007-Aminopyrazolo(4,3-d)pyrimidineYield 62.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

4-Nitro-1H-5-pyrazolecarbonitrile (6.25 g, 45.3 mmol) in ethanol (100 mL) was treated with 10% Palladium on carbon (0.50 g) and hydrogenated in a Parr shaker at 50 psi for 18 hours. The catalyst was removed by filtration through a pad of diatomaceous earth. The filtrate was then treated with formamidine acetate (37.7 g, 0.363 mol) then the mixture was heated at reflux for one hour. The mixture was cooled and then approximately 50 mL of the solvent was removed under reduced pressure. The precipitate which formed was isolated by filtration and washed with ethyl acetate (3×25 mL) then discarded. The filtrate was concentrated under reduced pressure to a volume of approximately 40 mL. The mixture was heated to dissolve all of the material then applied to a silica gel column which was eluted with ethyl acetate/methanol (8:2). The appropriate fractions were concentrated to give the title compound (3.85 g, 61%) which contained 18% formamidine acetate by weight as determined by 1H NMR: 1H NMR (DMSO-d6, 400 MHz) δ 13.3 bs, 1H), 8.15 (s, 1H) 8.07 (s, 1H), 7.47 (bs, 2H); RP-HPLC (Hypersil HS C18, 5 μm, 100 A, 250×4.6 mm; 5%-100% acetonitrile-0.05 M ammonium acetate over 25 min, 1 mL/min) tr 4.95 min; MS: MH+ 136.1, M−H+ 134.1

Workup

  1. customThe catalyst was removed by filtration through a pad of diatomaceous earth
  2. temperaturethe mixture was heated
  3. temperatureat reflux for one hour
  4. temperatureThe mixture was cooled
  5. customapproximately 50 mL of the solvent was removed under reduced pressure
  6. customThe precipitate which formed
  7. customwas isolated by filtration
  8. washwashed with ethyl acetate (3×25 mL)
  9. concentrationThe filtrate was concentrated under reduced pressure to a volume of approximately 40 mL
  10. temperatureThe mixture was heated
  11. dissolutionto dissolve all of the material
  12. washwas eluted with ethyl acetate/methanol (8:2)
  13. concentrationThe appropriate fractions were concentrated

Sources & evidence

ORD record
ord-7d90f24749d24034a2e5d18c84c1f108
Source dataset
uspto-grants-2010_11
Patent number
US07829570B2

Reaction notes

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