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

HRID 2278857Notes

Reaction equation

HRID 2278857 reaction equation
[F:1][C:2]1[CH:28]=[CH:27][CH:26]=[CH:25][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]([C:21]([F:24])([F:23])[F:22])=[C:18](O)[N:19]=2)=[N:6]1.P(Cl)(Cl)(Cl)=O.[NH3:34]>C(#N)C>[F:1][C:2]1[CH:28]=[CH:27][CH:26]=[CH:25][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]([C:21]([F:24])([F:23])[F:22])=[C:18]([NH2:34])[N:19]=2)=[N:6]1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 24813Phosphorus oxychlorideHCID 178517576HCID 178517576, compound

Product 1

HCID 716218403-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-(trifluoromethyl)-1,2,4-triazine-5-amine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

690 mg (1.768 mmol) of 3-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-(trifluoromethyl)-1,2,4-triazin-5-ol were admixed with 9 ml of phosphoryl chloride and stirred at RT overnight. The reaction mixture was diluted with 50 ml of dry acetonitrile and, with ice-cooling, stirred into 123 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, water was added, 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 125 mg (18% 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, water
  6. additionwas added
  7. filtrationthe precipitate was filtered 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-03f0cbfe73b148f69e957c141df1fa92
Source dataset
uspto-grants-2015_09
Patent number
US09133191B2

Reaction notes

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