Imidazole → HCID 131729654, compound

HRID 1696562Notes

Reaction equation

HRID 1696562 reaction equation
Cl.[NH2:2][C:3]1[N:7]([C:8]2[CH:9]=[C:10]([CH2:14][OH:15])[CH:11]=[CH:12][CH:13]=2)[N:6]=[C:5]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:4]=1.N1C=CN=C1.[CH3:25][C:26]([Si:29](Cl)(C)[CH3:30])([CH3:28])[CH3:27]>CN(C=O)C>[C:16]([C:5]1[CH:4]=[C:3]([NH2:2])[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][O:15][SiH:29]([C:26]([CH3:28])([CH3:27])[CH3:25])[CH3:30])[CH:9]=2)[N:6]=1)([CH3:19])([CH3:18])[CH3:17]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 67271901HCID 67271901, compound

Product 1

HCID 131729654HCID 131729654, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [3-(5-amino-3-t-butyl-1H-pyrazol-1-yl)phenyl]methanol hydrochloride salt (2.0 g, 7.1 mmol) in DMF (20 mL) was added imidazole (2.7 g, 39 mmol) and TBSCl (2.1 g, 14 mmol), which was stirred at RT for 8 h. The reaction mixture was quenched with water and extracted with EtOAc (3×). Organic extracts were washed with NaHCO3, H2O and 10% LiCl solution. The combined organic extracts were washed with brine, dried (Na2SO4), filtered, concentrated and purified via column chromatography to yield 3-t-butyl-1-(3-[(t-butylmethylsilyloxy)methyl]phenyl}-1H-pyrazol-5-amine in 36% yield (for three steps): 1H-NMR (CDCl3): δ 7.3-7.6 (m, 4H), 5.54 (s, 1H), 4.80 (s, 2H), 1.34 (s, 9H), 0.97 (s, 9H), 0.13 (s, 6H); MS (EI) m/z: 360 (M+H+).

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted with EtOAc (3×)
  3. washOrganic extracts were washed with NaHCO3, H2O and 10% LiCl solution
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified via column chromatography

Sources & evidence

ORD record
ord-19e8b572db144b4cad34d347f0c08439
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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