Methyl iodide → 6-Amino-2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]-7-methyl-7,9-dihydro-8H-purin-8-one

HRID 510106Notes

Reaction equation

HRID 510106 reaction equation
[F:1][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][C:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[N:7]([C:14]2[N:19]=[C:18]([NH2:20])[C:17]([NH2:21])=[C:16]([NH2:22])[N:15]=2)[N:6]=1.I[CH3:28].[O:29]1CCC[CH2:30]1>C(OCC)(=O)C>[NH2:20][C:18]1[N:19]=[C:14]([N:7]2[C:8]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[C:5]([CH2:4][C:3]3[CH:23]=[CH:24][CH:25]=[CH:26][C:2]=3[F:1])=[N:6]2)[N:15]=[C:16]2[C:17]=1[N:21]([CH3:28])[C:30](=[O:29])[NH:22]2

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 8028Tetrahydrofuran2×HCID 24794429HCID 24794429, compound

Product 1

HCID 666136126-Amino-2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]-7-methyl-7,9-dihydro-8H-purin-8-one

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

200 mg (0.392 mmol) of 2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidine-4,5,6-triamine (example 2A) were initially charged in tetrahydrofuran (11.1 ml) and the suspension was cooled to 0° C. Subsequently, 0.43 ml of a 1M solution of bis(trimethylsilyl)sodium amide in tetrahydrofuran was added and the mixture was stirred at 0° C. for a further 30 min. Thereafter, 24.4 μl (0.392 mmol) of iodomethane were added dropwise and the reaction mixture was stirred at RT overnight. The reaction mixture was again cooled to 0° C. and a further 12.2 μl (0.196 mmol) of iodomethane (dissolved in 1.0 ml of tetrahydrofuran) were added. Thereafter, the mixture was stirred at 0° C. for 1 h and then heated to reflux overnight. The reaction mixture was diluted with ethyl acetate and washed twice with saturated aqueous sodium hydrogencarbonate solution. The organic phase was dried over magnesium sulfate, filtered and concentrated by rotary evaporation. The residue was chromatographed on silica gel (eluent: dichloromethane/methanol 40:1) and the product fractions were concentrated. This gave 15.6 mg (10% of theory) of the title compound in solid form.

Workup

  1. stirringthe reaction mixture was stirred at RT overnight
  2. temperatureThe reaction mixture was again cooled to 0° C.
  3. stirringThereafter, the mixture was stirred at 0° C. for 1 h
  4. temperatureheated
  5. temperatureto reflux overnight
  6. washwashed twice with saturated aqueous sodium hydrogencarbonate solution
  7. dry with materialThe organic phase was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated by rotary evaporation
  10. customThe residue was chromatographed on silica gel (eluent: dichloromethane/methanol 40:1)
  11. concentrationthe product fractions were concentrated

Sources & evidence

ORD record
ord-e224b14e53ce495a8be786a2af0cba6c
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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