Tetrabutylammonium Fluoride → HCID 72204422, compound

HRID 711296Notes

Reaction equation

HRID 711296 reaction equation
[CH3:1][CH:2]([N:4]([CH2:21][C:22]1[C:30]2[C:25](=[N:26][CH:27]=[CH:28][CH:29]=2)[N:24](COCC[Si](C)(C)C)[CH:23]=1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([S:14]([C:17]([F:20])([F:19])[F:18])(=[O:16])=[O:15])=[CH:10][CH:9]=1)=[O:6])[CH3:3].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[CH3:3][CH:2]([N:4]([CH2:21][C:22]1[C:30]2[C:25](=[N:26][CH:27]=[CH:28][CH:29]=2)[NH:24][CH:23]=1)[C:5]([NH:7][C:8]1[CH:9]=[CH:10][C:11]([S:14]([C:17]([F:19])([F:20])[F:18])(=[O:16])=[O:15])=[CH:12][CH:13]=1)=[O:6])[CH3:1]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium Fluoride2×HCID 90014402HCID 90014402, compound

Product 1

HCID 72204422HCID 72204422, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 1-propan-2-yl-3-{4-[(trifluoromethyl)sulfonyl]phenyl}-1-[(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]urea (167 mg, 0.29 mmol) in 1 mL THF was added 1 M tetrabutylammonium fluoride in THF (1.46 mL, 1.46 mmol). The reaction was heated to reflux for 1 h then treated with additional 1M tetrabutylammonium fluoride in THF (0.73 mL, 0.73 mmol). The solution was heated to reflux for 16 h, cooled to ambient temperature, and partitioned between saturated NaHCO3 and ethylacetate. The organics were washed with water and brine, then dried over Na2SO4, filtered and concentrated. The residue was purified on a Gilson reverse phase preparatory instrument, followed by purification by silica gel chromatography (CH2Cl2/MeOH followed by ethylacetate/hexanes) to give 1-(1-methylethyl)-1-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-3-{4-[(trifluoromethyl)sulfonyl]phenyl}urea. 1H NMR (400 MHz, CD3 OD): δ 8.19 (dd, J=4.8, 1.5 Hz, 1 H); 8.12 (dd, J=7.9, 1.5 Hz, 1 H); 7.90 (d, J=8.9 Hz, 2 H); 7.77 (d, J=9.0 Hz, 2 H); 7.33 (s, 1 H); 7.11 (dd, J=7.9, 4.8 Hz, 1 H); 4.79 (s, 2 H); 4.53-4.47 (m, 1 H); 1.25 (d, J=6.7 Hz, 6 H). LCMS [M+H]+=441.1.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 1 h
  3. temperatureThe solution was heated
  4. temperatureto reflux for 16 h
  5. custompartitioned between saturated NaHCO3 and ethylacetate
  6. washThe organics were washed with water and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified on a Gilson reverse phase preparatory instrument
  11. customfollowed by purification by silica gel chromatography (CH2Cl2/MeOH followed by ethylacetate/hexanes)

Sources & evidence

ORD record
ord-0f2ae2c6bfd643ab961410135a223f9e
Source dataset
uspto-grants-2015_11
Patent number
US09181261B2

Reaction notes

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