Tetrabutylammonium Fluoride → HCID 71285864, compound

HRID 246235Notes

Reaction equation

HRID 246235 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([NH:11][C:12]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([C:23]4[C:31]5[C:26](=[CH:27][C:28]([F:32])=[CH:29][CH:30]=5)[N:25]([CH3:33])[N:24]=4)[N:21]=3)[N:16](COCC[Si](C)(C)C)[CH:15]=2)=[O:13])[CH3:10])=[CH:5][CH:4]=1)#[N:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C@H:9]([NH:11][C:12]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([C:23]4[C:31]5[C:26](=[CH:27][C:28]([F:32])=[CH:29][CH:30]=5)[N:25]([CH3:33])[N:24]=4)[N:21]=3)[NH:16][CH:15]=2)=[O:13])[CH3:10])=[CH:7][CH:8]=1)#[N:2]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 71288994HCID 71288994, compound

Product 1

HCID 71285864HCID 71285864, compoundYield 19%

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 [(R)-1-(4-cyanophenyl)-ethyl]-amide (32 mg, 0.056 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 with EtOAc. Brine was added and the aqueous layer was 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 7.5% MeOH in dichloromethane. The appropriate fractions were combined and concentrated to afford 4 mg (19%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-phenyl)-ethyl]-amide as a white solid. LC-MS (M+H)+=440; 1H NMR (300 MHz, DMSO-d6) δ: 12.97 (br. s., 1H), 9.17 (s, 1H), 8.33-8.69 (m, 3H), 7.85 (d, J=8.3 Hz, 2H), 7.64-7.78 (m, 3H), 7.08 (d, J=2.0 Hz, 1H), 5.39 (br. s., 1H), 4.20 (s, 3H), 1.70 (d, J=7.0 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 with EtOAc
  5. additionBrine was added
  6. extractionthe aqueous layer was extracted twice with EtOAc
  7. washThe combined organics were washed with water and brine
  8. dry with materialthen dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude solid was purified by flash chromatography (4 g silicycle) with 0% to 7.5% MeOH in dichloromethane
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-ff0a45d94d394da6b093d0e11e7c5ec2
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…