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

HRID 2278861Notes

Reaction equation

HRID 2278861 reaction equation
[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[CH:24][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:15]=[N:16][C:17]([CH2:21][CH2:22][CH3:23])=[C:18](O)[N:19]=2)=[N:6]1.P(Cl)(Cl)(Cl)=O.[NH3:33]>C(#N)C>[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[CH:24][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:15]=[N:16][C:17]([CH2:21][CH2:22][CH3:23])=[C:18]([NH2:33])[N:19]=2)=[N:6]1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 24813Phosphorus oxychlorideHCID 178440334HCID 178440334, compound

Product 1

HCID 716218443-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-propyl-1,2,4-triazine-5-amine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1.730 g (4.748 mmol) of 3-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-propyl-1,2,4-triazin-5-ol were admixed with 23 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 330 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 mixture was concentrated on a rotary evaporator, the residue was stirred with 200 ml of water and 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 1.360 g (60% 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. concentrationthe mixture was concentrated on a rotary evaporator
  6. stirringthe residue was stirred with 200 ml of water
  7. filtrationfiltered off with suction
  8. washthe filtercake was washed with a little water
  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-4b5b686d8d444ab0a68dc8e9a667c8c0
Source dataset
uspto-grants-2015_09
Patent number
US09133191B2

Reaction notes

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