Tetrabutylammonium Fluoride → HCID 71285775, compound

HRID 246274Notes

Reaction equation

HRID 246274 reaction equation
[O:1]1[CH2:4][CH:3]([C@H:5]([NH:7][C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[C:27]5[C:22](=[CH:23][C:24]([F:28])=[CH:25][CH:26]=5)[N:21]([CH3:29])[N:20]=4)[N:17]=3)[N:12](COCC[Si](C)(C)C)[CH:11]=2)=[O:9])[CH3:6])[CH2:2]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>>[O:1]1[CH2:2][CH:3]([C@H:5]([NH:7][C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[C:27]5[C:22](=[CH:23][C:24]([F:28])=[CH:25][CH:26]=5)[N:21]([CH3:29])[N:20]=4)[N:17]=3)[NH:12][CH:11]=2)=[O:9])[CH3:6])[CH2:4]1

Participants

3

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 71286083HCID 71286083, compound

Product 1

HCID 71285775HCID 71285775, compoundYield 64.5%

Conditions

Temperature
70 °C

Procedure

In a round-bottomed flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-oxetan-3-yl-ethyl)-amide (29 mg, 0.055 mmol) was dissolved in tetrabutylammonium fluoride (1.0 M in THF, 0.56 ml, 0.56 mmol). The light brown reaction mixture was stirred at 70° C. for 4 h then 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 chromatographed over silica gel with MeOH/CH2Cl2 (0.5% NH4OH) (gradient: 0-5% MeOH) to afford 14 mg (64%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-oxetan-3-yl-ethyl)-amide as a light yellow solid. Optical purity was determined to be 60% ee by chiral HPLC. MS: (M+Na)+=417; 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 12.87 (br. s., 1H), 9.10 (s, 1H), 8.46 (s, 1H), 8.42 (dd, J=8.8, 5.3 Hz, 1H), 8.07 (d, J=8.6 Hz, 1H), 7.71 (dd, J=9.9, 1.8 Hz, 1H), 7.25 (td, J=9.1, 2.0 Hz, 1H), 4.69 (dd, J=7.6, 6.1 Hz, 1H), 4.53-4.65 (m, 2H), 4.50 (t, J=6.1 Hz, 1H), 4.42 (t, J=6.3 Hz, 1H), 4.16 (s, 3H), 3.10-3.23 (m, 1H), 1.24 (d, J=6.6 Hz, 3H).

Workup

  1. temperaturethen cooled to room temperature
  2. customquenched with water
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialthen dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed over silica gel with MeOH/CH2Cl2 (0.5% NH4OH) (gradient: 0-5% MeOH)

Sources & evidence

ORD record
ord-0fb85a7f89824c9491ae4f2d47fcd402
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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