Nitrogen → HCID 86687279, compound

HRID 630966Notes

Reaction equation

HRID 630966 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.N#N.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 947NitrogenHCID 2723923Ammonium formate2×HCID 866872782-[3-((S)-2-Benzyloxy-1-methyl-ethoxy)-phenyl]-5-tert-butyl-2H-pyrazol-3-ylamine

Product 1

HCID 86687279HCID 86687279, compoundYield 86.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst3×HCID 702EthanolSolvent

Procedure

A solution of Intermediate 152a (0.39 g, 1.0 mmol) in ethanol (IMS grade, 10 mL) was purged with N2 then 10% Pd/C (0.11 g, 0.1 mmol Pd) was added. The mixture was purged with H2 then stirred under an atmosphere of H2 (balloon) at ambient temperature for 2 h, then at 50° C. for 1.5 h and 45° C. for 30 mins. Another portion of Pd/C (0.11 g, 0.1 mmol Pd) was added and the mixture was stirred at 45° C. for 16 h. The cooled reaction mixture was purged with N2 and treated with water (2 mL) then ammonium formate (0.65 g, 10.3 mmol) and heated to reflux for 5. Another portion of ammonium formate (0.65 g, 10.3 mmol) and Pd/C (0.11 g, 0.1 mmol) were added and the mixture was stirred at reflux for 16 h. The mixture was 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 (0.25 g, 83%) as a pink gum. LCMS (Method 3): Rt 2.44 min, m/z 290.3 [MH+].

Workup

  1. customThe mixture was purged with H2
  2. waitat 50° C. for 1.5 h
  3. wait45° C. for 30 mins
  4. stirringthe mixture was stirred at 45° C. for 16 h
  5. customThe cooled reaction mixture
  6. customwas purged with N2
  7. additiontreated with water (2 mL)
  8. temperatureto reflux for 5
  9. stirringthe mixture was stirred
  10. temperatureat reflux for 16 h
  11. filtrationThe mixture was filtered through celite
  12. concentrationthe filtrate was concentrated in vacuo
  13. customThe residue was partitioned between EtOAc and water
  14. customThe phases were separated
  15. extractionthe aqueous layer was extracted with EtOAc (×2)
  16. washThe combined organic phase was washed with saturated aqueous sodium bicarbonate solution and brine
  17. dry with materialdried (Na2SO4)
  18. concentrationconcentrated in vacuo
  19. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-ff29b821b55547a790a6184e29d64f80
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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