Tetrabutylammonium Fluoride → HCID 178447114, compound

HRID 2405900Notes

Reaction equation

HRID 2405900 reaction equation
C([Si]([C:8]1[C:13]([F:14])=[C:12]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[N:21][CH:22]=3)[NH:17][N:16]=2)[N:11]=[C:10]([N:24]2[CH2:29][CH2:28][NH:27][C@H:26]([C@:30]([CH3:39])([O:34][Si](C)(C)C)[CH:31]([CH3:33])[CH3:32])[CH2:25]2)[C:9]=1[F:40])(C)C)(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CCOC(C)=O>[F:40][C:9]1[C:10]([N:24]2[CH2:29][CH2:28][NH:27][C@H:26]([C@:30]([OH:34])([CH:31]([CH3:32])[CH3:33])[CH3:39])[CH2:25]2)=[N:11][C:12]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[N:21][CH:22]=3)[NH:17][N:16]=2)=[C:13]([F:14])[CH:8]=1

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 178447658HCID 178447658, compound

Product 1

HCID 178447114HCID 178447114, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl-[2-[(3S)-3-[(1R)-1,2-dimethyl-1-trimethylsilyloxy-propyl]piperazin-1-yl]-3,5-difluoro-6-(1H-pyrazolo[3,4-d]pyrimidin-3-yl)-4-pyridyl]-dimethyl-silane (134 mg, 0.23 mmol) in THF (3 mL) was added TBAF (1M in THF) (499.8 μL of 1 M, 0.50 mmol) and stirred at ambient temperature for 1 hour. After this time, the reaction mixture was diluted with EtOAc and the organics were washed with water (×3), brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 5 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min] The fractions were isolated and TFA was removed using PS-carbonate cartridge and freeze-dried to give the title compound as an off-white solid (38 mg, 40.2% Yield). H1 NMR (400.0 MHz, DMSO) δ 9.74 (s, 1H), 9.05 (s, 1H), 7.96 (dd, 1H), 4.15 (br s, 1H), 4.01 (d, 1H), 3.76 (d, 1H), 3.11 (d, 1H), 2.85 (d, 2H), 2.77-2.70 (m, 2H), 1.80 (quintet, 1H), 1.05 (s, 3H), 0.89 (d, 3H) and 0.84 (d, 3H) ppm; MS (ES+) 404.2.

Workup

  1. washthe organics were washed with water (×3), brine
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 5 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min] The fractions
  6. customwere isolated
  7. customTFA was removed
  8. customfreeze-dried

Sources & evidence

ORD record
ord-0d1d172c8815467e9538641cc046aa3a
Source dataset
uspto-grants-2014_08
Patent number
US08809335B2

Reaction notes

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