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

HRID 2278859Notes

Reaction equation

HRID 2278859 reaction equation
[CH:1]1([C:6]2[N:11]=[N:10][C:9]([C:12]3[C:20]4[C:15](=[N:16][CH:17]=[CH:18][CH:19]=4)[N:14]([CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[F:28])[N:13]=3)=[N:8][C:7]=2O)[CH2:5][CH2:4][CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)=O.[NH3:35]>C(#N)C>[CH:1]1([C:6]2[N:11]=[N:10][C:9]([C:12]3[C:20]4[C:15](=[N:16][CH:17]=[CH:18][CH:19]=4)[N:14]([CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[F:28])[N:13]=3)=[N:8][C:7]=2[NH2:35])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 24813Phosphorus oxychlorideHCID 178517575HCID 178517575, compound

Product 1

HCID 716218426-Cyclopentyl-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

730 mg (1.870 mmol) of 6-cyclopentyl-3-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-1,2,4-triazin-5-ol were admixed with 9 ml of phosphoryl chloride and stirred overnight at RT. The reaction mixture was diluted with 50 ml of dry acetonitrile and, with ice-cooling, stirred into 130 ml of concentrated aqueous ammonia solution (25% strength). Stirring was carried out for 48 h at RT and for 24 h at 50° C. After cooling, the acetonitrile was removed on a rotary evaporator, the precipitate was filtered off with suction and the filtercake was washed with a little water. The residue was purified by preparative HPLC (mobile phase: acetonitrile/water with 0.1% TFA, gradient 30:70→95:5). This gave 508 mg (70% of theory) of the target compound.

Workup

  1. temperaturecooling
  2. stirringStirring
  3. waitwas carried out for 48 h at RT and for 24 h at 50° C
  4. temperatureAfter cooling
  5. customthe acetonitrile was removed on a rotary evaporator
  6. filtrationthe precipitate was filtered off with suction
  7. washthe filtercake was washed with a little water
  8. 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-eb1260d905ba4a5ea1c507be15ca9ed1
Source dataset
uspto-grants-2015_09
Patent number
US09133191B2

Reaction notes

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