Water → 3-{5-Amino-3-[2-(tert-butyl-diphenyl-silanyloxy)-1,1-dimethyl-ethyl]-pyrazol-1-yl}-phenol

HRID 2285274Notes

Reaction equation

HRID 2285274 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]([N:15]2[C:19]([NH2:20])=[CH:18][C:17]([C:21]([CH3:42])([CH3:41])[CH2:22][O:23][Si:24]([C:37]([CH3:40])([CH3:39])[CH3:38])([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[N:16]2)[CH:12]=[CH:13][CH:14]=1)C1C=CC=CC=1.O.C([O-])=O.[NH4+]>C(O)C.[Pd]>[NH2:20][C:19]1[N:15]([C:11]2[CH:10]=[C:9]([OH:8])[CH:14]=[CH:13][CH:12]=2)[N:16]=[C:17]([C:21]([CH3:42])([CH3:41])[CH2:22][O:23][Si:24]([C:37]([CH3:40])([CH3:39])[CH3:38])([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:18]=1

Participants

6

Reactant 3

HCID 962WaterHCID 2723923Ammonium formateHCID 866872842-(3-Benzyloxy-phenyl)-5-[2-(tert-butyl-diphenyl-silanyloxy)-1,1-dimethyl-ethyl]-2H-pyrazol-3-ylamine

Product 1

HCID 866872853-{5-Amino-3-[2-(tert-butyl-diphenyl-silanyloxy)-1,1-dimethyl-ethyl]-pyrazol-1-yl}-phenolYield 52%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A solution of Intermediate 153c (1.21 g, 2.1 mmol) in ethanol (IMS grade, 20 mL) was treated with water (1 mL) and ammonium formate (1.33 g, 21 mmol). The mixture was purged with N2 then 10% Pd/C (0.67 g, 0.63 mmol Pd) was added. The mixture was heated to reflux for 1 h then filtered through celite and the filtrate was concentrated in vacuo. The residue was partitioned between EtOAc and water. The phases were separated and the aqueous layer was extracted with EtOAc (×2). The combined organic phase was washed with brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by FCC, using 0-40% EtOAc in cyclohexane, to give the title compound (0.53 g, 41% over 2 steps) as a golden gum. LCMS (Method 3): Rt 4.55 min, nth 486.5

Workup

  1. customThe mixture was purged with N2
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 1 h
  4. filtrationthen filtered through celite
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe residue was partitioned between EtOAc and water
  7. customThe phases were separated
  8. extractionthe aqueous layer was extracted with EtOAc (×2)
  9. washThe combined organic phase was washed with brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-af41cf52431f4de48360c1e85fa3316e
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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