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

HRID 510105Notes

Reaction equation

HRID 510105 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[CH2:28][CH3:29].[O:30]1CCC[CH2:31]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]([CH2:28][CH3:29])[C:31](=[O:30])[NH:22]2

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 8028TetrahydrofuranHCID 24794429HCID 24794429, compound

Product 1

HCID 666139886-Amino-7-ethyl-2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]-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 (0.43 mmol) of bis(trimethylsilyl)sodium amide solution (1.0 M in tetrahydrofuran) was added and the mixture was stirred at 0° C. for a further 30 min Thereafter, 31.3 μl (0.392 mmol) of iodoethane were added dropwise and the reaction mixture was stirred at RT overnight. The reaction mixture was cooled again to 0° C. and a further 0.47 ml (0.47 mmol) of bis(trimethylsilyl)sodium amide solution was added. Thereafter, the reaction mixture was stirred at RT overnight and heated to reflux for a further 2 days. Subsequently, 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 separated by means of preparative HPLC (eluent: acetonitrile-water with 0.1% formic acid gradient) and the product fractions were concentrated. The crude product was extracted by stirring in methyl tert-butyl ether, and the solids were filtered off and dried under high vacuum. This gave 4.6 mg (2.9% of theory) of the title compound in solid form.

Workup

  1. stirringthe reaction mixture was stirred at RT overnight
  2. temperatureThe reaction mixture was cooled again to 0° C.
  3. stirringThereafter, the reaction mixture was stirred at RT overnight
  4. temperatureheated
  5. temperatureto reflux for a further 2 days
  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 separated by means of preparative HPLC (eluent: acetonitrile-water with 0.1% formic acid gradient)
  11. concentrationthe product fractions were concentrated
  12. extractionThe crude product was extracted
  13. stirringby stirring in methyl tert-butyl ether
  14. filtrationthe solids were filtered off
  15. customdried under high vacuum

Sources & evidence

ORD record
ord-1a547e7b188f493ea8a6a50afdd5dcee
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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