2,2,2-Trifluoroethyl trifluoromethanesulfonate → HCID 10128827, compound

HRID 2068067Notes

Reaction equation

HRID 2068067 reaction equation
[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:34])[NH:6]2.FC(F)(F)S(O[CH2:41][C:42]([F:45])([F:44])[F:43])(=O)=O>CO>[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:33][CH2:32][N:31]([CH2:41][C:42]([F:45])([F:44])[F:43])[CH2:30][CH2:29]4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:34])[NH:6]2

Participants

4

Reactant 2

HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 58960233HCID 58960233, compound

Product 1

HCID 10128827HCID 10128827, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Using an analogous procedure to that described for the preparation of Example 14, 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-piperazin-1-ylpropoxy)quinazoline (250 mg, 0.54 mmol) was reacted with 2,2,2-trifluoroethyl trifluoromethanesulphonate (128 mg, 0.59 mmol) and purified by column chromatography, eluting with 5% methanol/methylene chloride to give a sticky solid. The sticky solid was dissolved in methanol and absorbed onto an Isolute SCX column. The column was washed with methanol and eluted with 7N ammonia in methanol. The product was triturated in ether/isohexane and filtered to give 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-{3-[4-(2,2,2-trifluoroethyl)piperazin-1-yl]propoxy}quinazoline (130 mg, 44%).

Workup

  1. custompurified by column chromatography
  2. washeluting with 5% methanol/methylene chloride
  3. customto give a sticky solid
  4. customabsorbed onto an Isolute SCX column
  5. washThe column was washed with methanol
  6. washeluted with 7N ammonia in methanol
  7. customThe product was triturated in ether/isohexane
  8. filtrationfiltered

Sources & evidence

ORD record
ord-ff1c870063aa4fa78d479bf4e29d0a7b
Source dataset
uspto-grants-2012_10
Patent number
US08293902B2

Reaction notes

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