Triethylamine → 3-iodo-1-[3-(4-methylpiperazino)propyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 898019Notes

Reaction equation

HRID 898019 reaction equation
Br[CH2:2][CH2:3][CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[N:12][C:13]([NH2:14])=[C:8]2[C:7]([I:15])=[N:6]1.[CH3:16][N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C(N(CC)CC)C>CN(C)C=O>[I:15][C:7]1[C:8]2[C:9](=[N:10][CH:11]=[N:12][C:13]=2[NH2:14])[N:5]([CH2:4][CH2:3][CH2:2][N:20]2[CH2:21][CH2:22][N:17]([CH3:16])[CH2:18][CH2:19]2)[N:6]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 223466991-(3-bromopropyl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 223466583-iodo-1-[3-(4-methylpiperazino)propyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 45.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of 1-(3-bromopropyl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.500 g, 1.31 mmol) in dimethylformamide (10 mL) was treated with 1-methylpiperazine (0.157 g, 1.572 mmol) and triethylamine (0.133 g, 1.31 mmol). The reaction mixture was stirred at 70° C. for 66.25 h. Solvent was removed under reduced pressure. Dichloromethane (15 mL) and 1 N hydrochloric acid (20 mL) were added. The layers were partitioned and the aqueous layer was washed with dichloromethane (100 mL). The aqueous layer was neutralized to pH 13 and then extracted with dichloromethane (250 mL). The organic layer was dried over magnesium sulfate, filtered and evaporated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a step-wise gradient; 20% methanol in dichloromethane to 50% methanol in dichloromethane over 55 minutes on a 35 g ISCO column. The column afforded 0.238 g (45%) of pure 3-iodo-1-[3-(4-methylpiperazino)propyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine. 1H NMR (DMSO-d6, 400 MHz) δ 8.191 (s, 1H), 4.308-4.273 (t, 2H), 2.262-2.228 (m, 10H), 1.944-1.877(m, 2H); LCMS (Thermoquest AQA single-quad MS, Genesis C18 column, 3 μm particle size, 33×4.6 mm; 70% 50 mM ammonium acetate in water to 95% acetonitrile over 6 min, 0.8 to 0.5 mL/min) Rt 0.75 min (100%), MH+ 402.1.

Workup

  1. customSolvent was removed under reduced pressure
  2. additionDichloromethane (15 mL) and 1 N hydrochloric acid (20 mL) were added
  3. customThe layers were partitioned
  4. washthe aqueous layer was washed with dichloromethane (100 mL)
  5. extractionextracted with dichloromethane (250 mL)
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe crude material was purified by flash chromatography on silica gel using a step-wise gradient
  10. wait20% methanol in dichloromethane to 50% methanol in dichloromethane over 55 minutes on a 35 g ISCO column

Sources & evidence

ORD record
ord-c3759a712c8542089ad485222915ce5f
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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