Tetrabutylammonium Fluoride → HCID 178517055, compound

HRID 1615281Notes

Reaction equation

HRID 1615281 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH2:7][CH2:8][C:9]2[C:17]3[C:12](=[CH:13][C:14]([CH:18]=[C:19]4[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[NH:21][C:20]4=[O:28])=[CH:15][CH:16]=3)[N:11](COCC[Si](C)(C)C)[N:10]=2)=[CH:3][CH:2]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[N:1]1[CH:6]=[CH:5][C:4]([CH2:7][CH2:8][C:9]2[C:17]3[C:12](=[CH:13][C:14]([CH:18]=[C:19]4[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[NH:21][C:20]4=[O:28])=[CH:15][CH:16]=3)[NH:11][N:10]=2)=[CH:3][CH:2]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 68758106HCID 68758106, compound

Product 1

HCID 178517055HCID 178517055, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3-((3-(2-(pyridin-4-yl)ethyl)-1-((2-(trimethylsilyl)ethoxy)-methyl)-1H-indazol-6-yl)methylene)indolin-2-one (57 mg, 0.115 mmol) in THF (3 mL) was treated with TBAF (0.58 mL of a 1.0 M solution in THF) and the reaction heated at reflux for 20 hours. The solvent was removed and the residue re-dissolved into EtOAc. The organics were washed with water (2×), brine (2×) and then dried (MgSO4). The solvent was removed and the residue purified by column chromatography (silica gel, 93:7 CH2Cl2/MeOH) to give a yellow solid which was impure by LC-MS. The mixture was further purified by prep-HPLC to give 11.3 mg, 27% of the title compound as a 76:24 mixture of (E)/(Z) geometric isomers. 1H NMR (400 MHz, CD3OD) δ 8.79, 7.87 (s, 1H), 8.69, 8.66 (d, J=6.52 Hz, 2H), 7.98-7.73 (m, 4H), 7.74, 7.62 (d, J=8.36 Hz, 1H), 7.66, 7.44 (d, J=8.44 Hz, 1H), 7.25, 7.05 (t, J=7.79 Hz, 1H), 6.95-6.84 (m, 2H), 3.53, 3.51 (s, 4H); MS ESI 367.2 [M+H]+, calcd for [C23H18N4O+H]+ 367.16.

Workup

  1. temperatureheated
  2. temperatureat reflux for 20 hours
  3. customThe solvent was removed
  4. dissolutionthe residue re-dissolved into EtOAc
  5. washThe organics were washed with water (2×), brine (2×)
  6. dry with materialdried (MgSO4)
  7. customThe solvent was removed
  8. customthe residue purified by column chromatography (silica gel, 93:7 CH2Cl2/MeOH)
  9. customto give a yellow solid which
  10. customThe mixture was further purified by prep-HPLC

Sources & evidence

ORD record
ord-9cd0a6bc9aa046b6a9dd495ff3b54b26
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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