3-Bromobenzonitrile → HCID 136140515, compound

HRID 1594400Notes

Reaction equation

HRID 1594400 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]2[NH:31][C:32](=[O:44])[CH2:33][CH:34]([C:35]3[CH:40]=[C:39]([F:41])[C:38]([F:42])=[CH:37][C:36]=3[F:43])[C:29]=2[C:28]([CH:45]2[CH2:48][C:47](=[O:49])[CH2:46]2)=[N:27]1)([CH3:25])([CH3:24])[CH3:23]>C1COCC1>[C:22]([N:26]1[C:30]2[NH:31][C:32](=[O:44])[CH2:33][CH:34]([C:35]3[CH:40]=[C:39]([F:41])[C:38]([F:42])=[CH:37][C:36]=3[F:43])[C:29]=2[C:28]([CH:45]2[CH2:48][C:47]([C:2]3[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=3)[C:5]#[N:6])([OH:49])[CH2:46]2)=[N:27]1)([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 4

HCID 233813-BromobenzonitrileHCID 18522661Acetone cardiceHCID 136140514HCID 136140514, compoundHCID 178418339Butyllithium

Product 1

HCID 136140515HCID 136140515, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 3-bromobenzonitrile (3.7 g, 20.4 mmol) in 50 mL of THF at −78° C. (acetone/CO2 bath) was added a solution of n-BuLi (8.2 mL, 20.4 mmol, 2.5 M in hexanes). After 15 min, a solution of 1-tert-butyl-3-(3-oxo-cyclobutyl)-4-(2,4,5-trifluoro-phenyl)-1,4,5,7-tetrahydro-pyrazolo[3,4-b]pyridin-6-one (2.0 g, 5.1 mmol in 10 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 CH2Cl2, and the layers were separated. The organic layer was dried over MgSO4, filtered through a pad of diatomaceous earth, and concentrated under reduced pressure to give a tan solid. Purification of this material was accomplished by MPLC using a 35 g ISCO cartridge on a Biotage® system eluting with a gradient of 25-50% EtOAc/hexanes. The product-containing fractions were collected and concentrated to yield the title compound (0.98 g, 40% yield) as a tan solid. Rf=0.29 (50% EtOAc/hexanes).

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 CH2Cl2
  4. customthe layers were separated
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered through a pad of diatomaceous earth
  7. concentrationconcentrated under reduced pressure
  8. customto give a tan solid
  9. customPurification of this material
  10. washeluting with a gradient of 25-50% EtOAc/hexanes
  11. customThe product-containing fractions were collected
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-5d0a6bad5cae414fbf7a6a75f345f6dd
Source dataset
uspto-grants-2007_11
Patent number
US07300944B2

Reaction notes

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