Water → HCID 86687277, compound

HRID 2285263Notes

Reaction equation

HRID 2285263 reaction equation
C([O:8][CH2:9][C@@H:10]([CH3:28])[O:11][C:12]1[CH:13]=[C:14]([N:18]2[C:22]([NH2:23])=[CH:21][C:20]([C:24]([CH3:27])([CH3:26])[CH3:25])=[N:19]2)[CH:15]=[CH:16][CH:17]=1)C1C=CC=CC=1.O.C([O-])=O.[NH4+]>C(O)C.[Pd]>[NH2:23][C:22]1[N:18]([C:14]2[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=2)[O:11][C@H:10]([CH3:28])[CH2:9][OH:8])[N:19]=[C:20]([C:24]([CH3:25])([CH3:27])[CH3:26])[CH:21]=1

Participants

6

Reactant 3

HCID 962WaterHCID 2723923Ammonium formateHCID 866872762-[3-((R)-2-Benzyloxy-1-methyl-ethoxy)-phenyl]-5-tert-butyl-2H-pyrazol-3-ylamine

Product 1

HCID 86687277HCID 86687277, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A solution of Intermediate 151a (0.37 g, 0.97 mmol) in ethanol (IMS grade, 8 mL) was treated with water (1 mL) and ammonium formate (0.61 g, 9.7 mmol). The mixture was purged with N2 then 10% Pd/C (0.31 g, 0.29 mmol Pd) was added. The mixture was heated to reflux for 16 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 saturated aqueous sodium bicarbonate solution and brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by FCC, using 0-75% EtOAc in cyclohexane to give the title compound (0.22 g, 79%) as a pink gum. LCMS (Method 3): Rt 2.44 min, m/z 290.3 [MH+].

Workup

  1. customThe mixture was purged with N2
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 16 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 saturated aqueous sodium bicarbonate solution and brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-49ddc5ddc22b4411a0a858c8aa2feb5b
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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