Pyrazole → HCID 89545001, compound

HRID 2283399Notes

Reaction equation

HRID 2283399 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.[H-].[Na+].C(OC(=O)[NH:14][C@@H:15]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([C:25]([C:27]2[CH:28]=[N:29][C:30](Cl)=[CH:31][CH:32]=2)=[O:26])[C:19]=1[F:34])[CH2:16][CH3:17])(C)(C)C>CN(C=O)C>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([C@H:15]([NH2:14])[CH2:16][CH3:17])=[C:19]([F:34])[C:20]=1[C:25]([C:27]1[CH:28]=[N:29][C:30]([N:1]2[CH:5]=[CH:4][CH:3]=[N:2]2)=[CH:31][CH:32]=1)=[O:26]

Participants

5

Reactant 3

HCID 1048PyrazoleHCID 24758Sodium hydrideHCID 89544738HCID 89544738, compound

Product 1

HCID 89545001HCID 89545001, compoundYield 72.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To Pyrazole (0.016 g, 0.23 mmol) in DMF (2 ml) added sodium hydride (60%) (0.01 g, 0.25 mmol) then stirred at ambient for 15 minutes. {(R)-1-[4-Chloro-3-(6-chloro-pyridine-3-carbonyl)-2-fluoro-phenyl]-propyl}-carbamic acid tert-butyl ester [from Example 1, step 1] (0.1 g, 0.23 mmol) in DMF (2 ml) added dropwise, stirred at ambient for 1 hour, reaction quenched using water and extracted with EtOAc. The organic extract was dried (Na2SO4), filtered and concentrated, MS: [M+H] 459. Residue treated with saturated HCl/EtOAc stirred at ambient for 1 hour. Mixture was concentrated, solid triturated with EtOAc, filtered and washed with EtOAC to give (1R)-1-(4-chloro-2-fluoro-3-{[6-(1H-pyrazol-1-yl)pyridin-3-yl]carbonyl}phenyl)propan-1-amine (0.06 g).

Workup

  1. stirringstirred at ambient for 1 hour
  2. customreaction
  3. customquenched
  4. extractionextracted with EtOAc
  5. extractionThe organic extract
  6. dry with materialwas dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. additionResidue treated with saturated HCl/EtOAc
  10. stirringstirred at ambient for 1 hour
  11. concentrationMixture was concentrated
  12. customsolid triturated with EtOAc
  13. filtrationfiltered
  14. washwashed with EtOAC

Sources & evidence

ORD record
ord-e685cc95250e4d49804905ee15ffa057
Source dataset
uspto-grants-2015_09
Patent number
US09145354B2

Reaction notes

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