Potassium Carbonate → Rac-3-iodo-1-[1-(2-methoxyethyl)tetrahydro-1h-3-pyrrolyl]-1h-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 2056122Notes

Reaction equation

HRID 2056122 reaction equation
Cl.[I:2][C:3]1[C:11]2[C:6](=[N:7][CH:8]=[N:9][C:10]=2[NH2:12])[N:5]([CH:13]2[CH2:17][CH2:16][NH:15][CH2:14]2)[N:4]=1.Br[CH2:19][CH2:20][O:21][CH3:22].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.[I-].[K+]>[I:2][C:3]1[C:11]2[C:6](=[N:7][CH:8]=[N:9][C:10]=2[NH2:12])[N:5]([CH:13]2[CH2:17][CH2:16][N:15]([CH2:19][CH2:20][O:21][CH3:22])[CH2:14]2)[N:4]=1

Participants

6

Reactant 3

HCID 11430Potassium Carbonate2×HCID 809722-Bromoethyl methyl ether2×HCID 223473313-iodo-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine hydrochloride

Product 1

HCID 69203235Rac-3-iodo-1-[1-(2-methoxyethyl)tetrahydro-1h-3-pyrrolyl]-1h-pyrazolo[3,4-d]pyrimidin-4-amineYield 84%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of rac-3-iodo-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine mono hydrochloride (0.350 g, 1.09 mmol) in N,N-dimethylformamide (10 mL) was added 2-bromoethylmethyl ether (0.159 g, 0.11 mL, 1.15 mmol), potassium carbonate (0.462 g, 3.34 mmol), and potassium iodide (0.008 g, 0.05 mmol). The reaction mixture stirred at 65° C. for 18 h and then additional 2-bromoethylmethyl ether (0.066 g, 0.040 mL, 0.48 mmol), potassium carbonate (0.130 g, 0.940 mmol), and potassium iodide (0.008 g, 0.05 mmol) were added. The reaction mixture was stirred for an additional 18 h and was then concentrated. The residue was partitioned between dichloromethane (10 mL) and water (10 mL). The organic phase was separated, washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated to afford rac-3-iodo-1-[1-(2-methoxyethyl)tetrahydro-1H-3-pyrrolyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a yellow solid (0.313 g, 84%) which was used in subsequent reactions without further purification. RP-HPLC Rt 5.089 min, 80% purity (5% to 85% acetonitrile/0.1M aqueous ammonium acetate, buffered to pH 4.5, over 20 min at 1 mL/min; λ=254 nm; Deltapak C18, 300 Å, 5 μm, 150×3.9 mm column); m/z 389 (MH+).

Workup

  1. stirringThe reaction mixture was stirred for an additional 18 h
  2. concentrationwas then concentrated
  3. customThe residue was partitioned between dichloromethane (10 mL) and water (10 mL)
  4. customThe organic phase was separated
  5. washwashed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-ba903f0ab0834b81a7d872d6afe5581d
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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