Tetrabutylammonium Fluoride → HCID 71285779, compound

HRID 246236Notes

Reaction equation

HRID 246236 reaction equation
[C:1]([CH2:3][O:4][CH2:5][C@@H:6]([NH:8][C:9]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17]([C:20]3[C:28]4[C:23](=[CH:24][C:25]([F:29])=[CH:26][CH:27]=4)[N:22]([CH3:30])[N:21]=3)[N:18]=2)[N:13](COCC[Si](C)(C)C)[CH:12]=1)=[O:10])[CH3:7])#[N:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:1]([CH2:3][O:4][CH2:5][C@@H:6]([NH:8][C:9]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17]([C:20]3[C:28]4[C:23](=[CH:24][C:25]([F:29])=[CH:26][CH:27]=4)[N:22]([CH3:30])[N:21]=3)[N:18]=2)[NH:13][CH:12]=1)=[O:10])[CH3:7])#[N:2]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 712860532-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-cyanomethoxy-1-methyl-ethyl)-amide

Product 1

HCID 71285779HCID 71285779, compoundYield 16.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a round-bottomed flask containing 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-cyanomethoxy-1-methyl-ethyl)-amide (55 mg, 0.102 mmol) dissolved in THF (1 ml) was added TBAF (1.0 M in THF, 1.0 ml, 1.0 mmol). The flask was backfilled with nitrogen then sealed and placed in an oil bath at 85° C. for 2 h. The reaction was cooled to room temperature, quenched with acetone (2 ml) and sat'd NaHCO3 (4 ml). The mixture was stirred for 1 h then diluted with water and extracted twice with EtOAc. The combined organics were washed with water and brine then dried over MgSO4, filtered and concentrated. The crude solid was purified by flash chromatography (4 g silicycle) with 0% to 10% MeOH in dichloromethane. The appropriate fractions were combined and concentrated. The solid was triturated with Et2O to afford 7 mg (16%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-cyanomethoxy-1-methyl-ethyl)-amide as a light brown solid. LC-MS (M+H)+=408; 1H NMR (300 MHz, DMSO-d6) δ: 12.95 (br. s., 1H), 9.17 (s, 1H), 8.47-8.62 (m, 2H), 8.26 (d, J=8.5 Hz, 1H), 7.76 (dd, J=9.8, 2.0 Hz, 1H), 7.25 (td, J=9.0, 2.3 Hz, 1H), 4.57 (s, 2H), 4.43-4.53 (m, 1H), 4.21 (s, 3H), 3.66-3.85 (m, 2H), 1.40 (d, J=6.8 Hz, 3H).

Workup

  1. customthen sealed
  2. customquenched with acetone (2 ml) and sat'd NaHCO3 (4 ml)
  3. additionthen diluted with water
  4. extractionextracted twice with EtOAc
  5. washThe combined organics were washed with water and brine
  6. dry with materialthen dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude solid was purified by flash chromatography (4 g silicycle) with 0% to 10% MeOH in dichloromethane
  10. concentrationconcentrated
  11. customThe solid was triturated with Et2O

Sources & evidence

ORD record
ord-73e918d7a1eb48619613960caef0d451
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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