Ammonia → (S)-5-Methyl-3-phenyl-2-(1-((5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)pyrrolo[2,1-f][1,2,4]triazin-4(3H)-one

HRID 1052779Notes

Reaction equation

HRID 1052779 reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([C:6]2[C:14]3[C:13]([NH:15][C@H:16]([C:18]4[N:23]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[C:22](=[O:30])[C:21]5=[C:31]([CH3:34])[CH:32]=[CH:33][N:20]5[N:19]=4)[CH3:17])=[N:12][CH:11]=[N:10][C:9]=3[N:8](COCC[Si](C)(C)C)[CH:7]=2)=[N:2]1.[F:43][C:44]([F:48])([F:47])[CH2:45]I.C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)C(O)=O.N>CN(C=O)C>[CH3:34][C:31]1[CH:32]=[CH:33][N:20]2[C:21]=1[C:22](=[O:30])[N:23]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]([C@@H:16]([NH:15][C:13]1[C:14]3[C:6]([C:3]4[CH:4]=[CH:5][N:1]([CH2:45][C:44]([F:48])([F:47])[F:43])[N:2]=4)=[CH:7][NH:8][C:9]=3[N:10]=[CH:11][N:12]=1)[CH3:17])=[N:19]2

Participants

7

Reactant 5

HCID 222AmmoniaHCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 677091,1,1-Trifluoro-2-iodoethaneHCID 178428095HCID 178428095, compound

Product 1

HCID 136623660(S)-5-Methyl-3-phenyl-2-(1-((5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)pyrrolo[2,1-f][1,2,4]triazin-4(3H)-oneYield 12.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

(S)-2-(1-((5-(1H-Pyrazol-3-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (50 mg, 0.07 mmol) and 1,1,1-trifluoro-2-iodoethane (36 mg, 0.17 mmol) were dissolved in DMF (2 ml) and cesium carbonate (140 mg, 0.43 mmol) was added. After stirring the mixture at 80° C. for 2 h, the solvent was evaporated under reduced pressure and the residue was suspended in water and extracted with ethyl acetate (×3). The organic phase was successively washed with water and brine, dried over magnesium sulphate, filtered and the solvent evaporated under reduced pressure. The residue (54 mg) was treated with trifluoroacetic acid (1 mL, 13 mmol) and a solution of ammonia (7N in methanol, 10 ml, 70 mmol) according to the method described in Example 27 to give 4.6 mg (12% yield) of the title compound. Purity 93%.

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. extractionextracted with ethyl acetate (×3)
  3. washThe organic phase was successively washed with water and brine
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure

Sources & evidence

ORD record
ord-4e66e3cd75524883a75ad8a9617e14a1
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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