Ammonia → 6-Ethyl-3-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-1,2,4-triazine-5-amine

HRID 2278863Notes

Reaction equation

HRID 2278863 reaction equation
[CH2:1]([C:3]1[N:8]=[N:7][C:6]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])[N:10]=2)=[N:5][C:4]=1O)[CH3:2].P(Cl)(Cl)(Cl)=O.[NH3:32]>C(#N)C>[CH2:1]([C:3]1[N:8]=[N:7][C:6]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])[N:10]=2)=[N:5][C:4]=1[NH2:32])[CH3:2]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 24813Phosphorus oxychlorideHCID 178437953HCID 178437953, compound

Product 1

HCID 716218466-Ethyl-3-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-1,2,4-triazine-5-amine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1.800 g (5.138 mmol) of 6-ethyl-3-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-1,2,4-triazin-5-ol were admixed with 25 ml of phosphoryl chloride and stirred overnight at RT. The reaction mixture was diluted with 100 ml of dry acetonitrile and, with ice-cooling, stirred into 375 ml of concentrated aqueous ammonia solution (25% strength). Stirring was carried out for 4 h at RT. Concentration on a rotary evaporator was carried out and the residue was partitioned between water and ethyl acetate. The organic phase was dried over sodium sulphate and concentrated on a rotary evaporator. The residue was purified by preparative HPLC (mobile phase: acetonitrile/water with 0.1% TFA, gradient 30:70→95:5). This gave 157 mg (8% of theory) of the target compound.

Workup

  1. temperaturecooling
  2. stirringStirring
  3. waitwas carried out for 4 h at RT
  4. concentrationConcentration
  5. customon a rotary evaporator
  6. customthe residue was partitioned between water and ethyl acetate
  7. dry with materialThe organic phase was dried over sodium sulphate
  8. concentrationconcentrated on a rotary evaporator
  9. customThe residue was purified by preparative HPLC (mobile phase: acetonitrile/water with 0.1% TFA, gradient 30:70→95:5)

Sources & evidence

ORD record
ord-fb4d2e9b7e534427901d81a03962c8c3
Source dataset
uspto-grants-2015_09
Patent number
US09133191B2

Reaction notes

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