3-Bromobenzonitrile → N-{2-tert-Butyl-5-[3-(3-cyano-phenyl)-3-hydroxy-cyclobutyl]-2H-pyrazol-3-yl}-2,2,2-trifluoro-acetamide

HRID 1594405Notes

Reaction equation

HRID 1594405 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].CC(C)=O.C(=O)=O.[Li]CCCC.[C:22]([N:26]1[C:30]([NH:31][C:32](=[O:37])[C:33]([F:36])([F:35])[F:34])=[CH:29][C:28]([CH:38]2[CH2:41][C:40](=[O:42])[CH2:39]2)=[N:27]1)([CH3:25])([CH3:24])[CH3:23]>C1COCC1>[C:22]([N:26]1[C:30]([NH:31][C:32](=[O:37])[C:33]([F:36])([F:34])[F:35])=[CH:29][C:28]([CH:38]2[CH2:41][C:40]([C:2]3[CH:9]=[CH:8][CH:7]=[C:4]([C:5]#[N:6])[CH:3]=3)([OH:42])[CH2:39]2)=[N:27]1)([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 4

HCID 233813-BromobenzonitrileHCID 18522661Acetone cardiceHCID 57525638N-[2-tert-Butyl-5-(3-oxo-cyclobutyl)-2H-pyrazol-3-yl]-2,2,2-trifluoro-acetamideHCID 178418339Butyllithium

Product 1

HCID 57525639N-{2-tert-Butyl-5-[3-(3-cyano-phenyl)-3-hydroxy-cyclobutyl]-2H-pyrazol-3-yl}-2,2,2-trifluoro-acetamideYield 98.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 3-bromobenzonitrile (12.6 g, 69.0 mmol) in 245 mL of THF at −78° C. (acetone/CO2 bath) was added a solution of n-BuLi (27.6 ml, 69 mmol, 2.5 M in hexanes). After 15 min, a solution of N-[2-tert-butyl-5-(3-oxo-cyclobutyl)-2H-pyrazol-3-yl]-2,2,2-trifluoro-acetamide (4.0 g, 11.5 mmol in 200 mL of THF) was added. After one hr, the reaction mixture was quenched cold by the addition of a saturated NH4Cl solution, and was then allowed to warm to room temperature. The reaction mixture was diluted with EtOAc, and the layers were separated. The organic layer was washed with brine, dried over MgSO4, filtered through a pad of diatomaceous earth, and concentrated under reduced pressure. Purification of this material was accomplished by MPLC using a Biotage® column, eluting with 25% EtOAc/hexanes. The product-containing fractions were collected and concentrated to yield the title compound (4.6 g, 98% yield). LRMS m/z (APCI+) 407 (M+1).

Workup

  1. waitAfter one hr
  2. customthe reaction mixture was quenched cold by the addition of a saturated NH4Cl solution
  3. additionThe reaction mixture was diluted with EtOAc
  4. customthe layers were separated
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered through a pad of diatomaceous earth
  8. concentrationconcentrated under reduced pressure
  9. customPurification of this material
  10. washeluting with 25% EtOAc/hexanes
  11. customThe product-containing fractions were collected
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-df46f502e4bf42008ea88abf4ce60565
Source dataset
uspto-grants-2007_11
Patent number
US07300944B2

Reaction notes

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