Methanol → HCID 69492268, compound

HRID 916426Notes

Reaction equation

HRID 916426 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.[CH3:48]O>>[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]([CH2:34][CH3:48])[NH:6]2

Participants

4

Reactant 3

HCID 887MethanolHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 58960233HCID 58960233, compound

Product 1

HCID 69492268HCID 69492268, compoundYield 44%

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-ethyl-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-2f9c0819e55045ebbf62031aea2ed23a
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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