(Trimethylsilyl)imidazole → HCID 178447658, compound

HRID 2405899Notes

Reaction equation

HRID 2405899 reaction equation
[C:1]([Si:5]([CH3:25])([CH3:24])[C:6]1[C:11]([F:12])=[C:10]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[N:19][CH:20]=3)[NH:15][N:14]=2)[N:9]=[C:8](F)[C:7]=1[F:23])([CH3:4])([CH3:3])[CH3:2].[CH3:26][CH:27]([CH3:37])[C@:28]([C@@H:31]1[CH2:36][NH:35][CH2:34][CH2:33][NH:32]1)([OH:30])[CH3:29].N1([Si:43]([CH3:46])([CH3:45])[CH3:44])C=CN=C1>C1COCC1.CCOC(C)=O>[Si:5]([C:6]1[C:7]([F:23])=[C:8]([N:35]2[CH2:34][CH2:33][NH:32][C@H:31]([C@:28]([O:30][Si:43]([CH3:46])([CH3:45])[CH3:44])([CH:27]([CH3:37])[CH3:26])[CH3:29])[CH2:36]2)[N:9]=[C:10]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[N:19][CH:20]=3)[NH:15][N:14]=2)[C:11]=1[F:12])([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:25])[CH3:24]

Participants

6

Reactant 3

HCID 28925(Trimethylsilyl)imidazoleHCID 66806074HCID 66806074, compoundHCID 178454990HCID 178454990, compound

Product 1

HCID 178447658HCID 178447658, compoundYield 54.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

tert-butyl-dimethyl-[2,3,5-trifluoro-6-(1H-pyrazolo[3,4-d]pyrimidin-3-yl)-4-pyridyl]silane (170 mg, 0.42 mmol), (2R)-3-methyl-2-[(2S)-piperazin-2-yl]butan-2-ol (109.8 mg, 0.64 mmol), imidazol-1-yl-trimethyl-silane (297.9 mg, 310.3 μL, 2.12 mmol) were dissolved in THF (420 μL). The reaction mixture was heated at 90° C. for 2 days under sealed tube conditions. After this time, the reaction mixture was allowed to cool to ambient temperature and diluted with EtOAc, washed with saturated aqueous NaHCO3, water, brine, dried (MgSO4), filtered and concentrated in vacuo. The crude mixture was purified by column chromatography (ISCO Companion™, 24 g column, eluting with 1-5% NH4OH:MeOH (1:9)/DCM) to give the sub title compound as cream solid 134 mg, 53.5% Yield). H1 NMR (400 MHz, DMSO) δ 14.26 (H, d), 9.66 (H, s), 8.97 (H, s), 3.82 (H, d), 3.60 (H, d), 3.06 (H, dd), 3.72 (4H, m), 1.75 (2H, m), 1.10 (3H, d), 0.80 (15H, m), 0.35 (6H, s) and 0.00 (9H, s).

Workup

  1. customunder sealed tube conditions
  2. temperatureto cool to ambient temperature
  3. washwashed with saturated aqueous NaHCO3, water, brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude mixture was purified by column chromatography (ISCO Companion™, 24 g column, eluting with 1-5% NH4OH:MeOH (1:9)/DCM)

Sources & evidence

ORD record
ord-e07480b5776b4daa9842b72ea76479ed
Source dataset
uspto-grants-2014_08
Patent number
US08809335B2

Reaction notes

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