Tetrabutylammonium Fluoride → HCID 178449397, compound

HRID 246314Notes

Reaction equation

HRID 246314 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[C:21]([C:26](C)(C)[O:27][SiH2]C(C)(C)C)[CH:22]=[CH:23][CH:24]=4)[NH:19][N:18]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[C:21]([CH2:26][OH:27])[CH:22]=[CH:23][CH:24]=4)[NH:19][N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 178449394HCID 178449394, compound

Product 1

HCID 178449397HCID 178449397, compoundYield 41.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a round-bottomed flask, 2-[7-(tert-butyl-dimethyl-silanyloxymethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (85 mg, 0.14 mmol) was dissolved in THF (0.7 ml) and tetrabutylammonium fluoride (1.0 M in THF, 1.4 ml, 1.4 mmol) was added dropwise. The light brown solution was stirred at room temperature for 10 min then heated at 70° C. for 2.5 h. The reaction mixture was cooled to room temperature, quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was absorbed on silica gel and chromatographed with MeOH/CH2Cl2/0.5% NH4OH (gradient: 0-10% MeOH). The appropriate fractions were combined and concentrated and the residue was triturated with ethyl acetate containing a few drops of methanol to afford 21 mg (41%) of 2-(7-hydroxymethyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as an off-white powder. MS: (M+Na)'=387; 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 13.49 (s, 1H), 12.77 (s, 1H), 9.15 (s, 1H), 8.39 (d, J=8.1 Hz, 1H), 8.36 (d, J=3.0 Hz, 1H), 8.01 (s, 1H), 7.38-7.46 (m, 1H), 7.16-7.25 (m, 1H), 5.37 (t, J=5.6 Hz, 1H), 4.88 (d, J=5.6 Hz, 2H), 1.53 (s, 9H).

Workup

  1. temperaturethen heated at 70° C. for 2.5 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customquenched with water
  4. extractionextracted with EtOAc (2×)
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialthen dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was absorbed on silica gel
  10. customchromatographed with MeOH/CH2Cl2/0.5% NH4OH (gradient: 0-10% MeOH)
  11. concentrationconcentrated
  12. customthe residue was triturated with ethyl acetate containing a few drops of methanol

Sources & evidence

ORD record
ord-9143c29488f94f43abac960e0d51f9a2
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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