Dimethylformamide → 3-[((2S)-2-methyl-4-{[4-(trifluoromethyl)phenyl]sulfonyl}-1-piperazinyl)carbonyl]pyrazolo[1,5-a]pyrimidine-6-carbonitrile

HRID 418307Notes

Reaction equation

HRID 418307 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[CH:9][C:10]=2[C:11]([N:13]2[CH2:18][CH2:17][N:16]([S:19]([C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=3)(=[O:21])=[O:20])[CH2:15][C@@H:14]2[CH3:32])=[O:12])[CH:7]=1.[CH3:33][N:34](C)C=O>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:32][C@H:14]1[CH2:15][N:16]([S:19]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH2:17][CH2:18][N:13]1[C:11]([C:10]1[CH:9]=[N:8][N:6]2[CH:7]=[C:2]([C:33]#[N:34])[CH:3]=[N:4][C:5]=12)=[O:12]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 66649655HCID 66649655, compound

Product 1

HCID 666497243-[((2S)-2-methyl-4-{[4-(trifluoromethyl)phenyl]sulfonyl}-1-piperazinyl)carbonyl]pyrazolo[1,5-a]pyrimidine-6-carbonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
95 °C

Procedure

To a mixture of 6-bromo-3-[((2S)-2-methyl-4-{[4-(trifluoromethyl)phenyl]sulfonyl}-1-piperazinyl)carbonyl]pyrazolo[1,5-a]pyrimidine (may be prepared as described in Example 12) (300 mg, 0.564 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (39.1 mg, 0.070 mmol) under argon in dry N,N-dimethylformamide (6 mL) was added zinc cyanide (86 mg, 0.733 mmol) followed by tris(dibenzylideneacetone)dipalladium(0) (32.0 mg, 0.035 mmol) and the mixture heated to 95° C. for 2 h. The mixture was partitioned between ethyl acetate (30 mL) and aqueous sodium bicarbonate (20 mL). The organic phase was washed with further sodium bicarbonate (10 mL), water (10 mL) and brine (10 mL) before it was dried (MgSO4), filtered and the solvent removed in vacuo. Half the crude material was purified by MDAP and the solvent evaporated to give the title compound (67 mg) as a yellow solid.

Workup

  1. customThe mixture was partitioned between ethyl acetate (30 mL) and aqueous sodium bicarbonate (20 mL)
  2. washThe organic phase was washed with further sodium bicarbonate (10 mL), water (10 mL) and brine (10 mL) before it
  3. dry with materialwas dried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent removed in vacuo
  6. customHalf the crude material was purified by MDAP
  7. customthe solvent evaporated

Sources & evidence

ORD record
ord-1bf996c49f41405f82861e16e2ab70dc
Source dataset
uspto-grants-2012_01
Patent number
US08093249B2

Reaction notes

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