Hydrochloric Acid → 5-tert-Butyl-2-[3-(4,4-difluoro-piperidin-1-ylmethyl)-phenyl]-2H-pyrazol-3-ylamine

HRID 75586Notes

Reaction equation

HRID 75586 reaction equation
[F:1][C:2]1([F:31])[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[C:11]([N:15](C(OC(C)(C)C)=O)[NH:16]C(OC(C)(C)C)=O)[CH:12]=[CH:13][CH:14]=2)[CH2:4][CH2:3]1.[C:32]([CH2:38][C:39]#[N:40])(=O)[C:33]([CH3:36])([CH3:35])[CH3:34].Cl.C([O-])(O)=O.[Na+]>C(O)C>[C:33]([C:32]1[CH:38]=[C:39]([NH2:40])[N:15]([C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([CH2:8][N:5]3[CH2:4][CH2:3][C:2]([F:31])([F:1])[CH2:7][CH2:6]3)[CH:10]=2)[N:16]=1)([CH3:36])([CH3:35])[CH3:34]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 108871Pentanenitrile, 4,4-dimethyl-3-oxo-HCID 516892Sodium BicarbonateHCID 86686689Di-tert-butyl 1-{3-[(4,4-difluoropiperidin-1-yl)methyl]phenyl}hydrazine-1,2-dicarboxylate

Product 1

HCID 866866905-tert-Butyl-2-[3-(4,4-difluoro-piperidin-1-ylmethyl)-phenyl]-2H-pyrazol-3-ylamineYield 43.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of Intermediate 12b (1.30 g, 2.94 mmol), pivaloyl acetonitrile (0.37 g, 2.94 mmol), and concentrated HCl (1.5 mL) in ethanol (10 mL) was heated under reflux for 3 h. The cooled mixture was taken to ca. pH 7 with aqueous saturated NaHCO3, and the mixture partitioned between water (15 mL) and EtOAc (3×15 mL). The combined organic extracts were washed with brine (20 mL) and dried (Na2SO4). The solvent was evaporated, and the residue purified by FCC, eluting with 0-100% EtOAc in pentane, to give the title compound as a pale yellow solid (450 mg, 43%). LCMS (Method 1): Rt 1.93 min, m/z 349 [MH+].

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 3 h
  3. customthe mixture partitioned between water (15 mL) and EtOAc (3×15 mL)
  4. washThe combined organic extracts were washed with brine (20 mL)
  5. dry with materialdried (Na2SO4)
  6. customThe solvent was evaporated
  7. customthe residue purified by FCC
  8. washeluting with 0-100% EtOAc in pentane

Sources & evidence

ORD record
ord-47aac7a30f7c456298af87f43839d7a4
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

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