N,N,N',N'-Tetramethylethylenediamine → 4-Methyl-6-(4-(1-(5-methylpyrazin-2-yl)piperidin-4-yl)piperidin-1-yl)pyrimidine-2-carbonitrile

HRID 2093481Notes

Reaction equation

HRID 2093481 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH:11]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]4[CH:25]=[N:24][C:23]([CH3:26])=[CH:22][N:21]=4)[CH2:16][CH2:15]3)[CH2:10][CH2:9]2)[CH:5]=[C:4]([CH3:27])[N:3]=1.C1(P(C2C=CC=CC=2)CCCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:59][N:60](C)CCN(C)C.[C-]#N.[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH3:27][C:4]1[CH:5]=[C:6]([N:8]2[CH2:13][CH2:12][CH:11]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]4[CH:25]=[N:24][C:23]([CH3:26])=[CH:22][N:21]=4)[CH2:16][CH2:15]3)[CH2:10][CH2:9]2)[N:7]=[C:2]([C:59]#[N:60])[N:3]=1

Participants

7

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 9032Potassium CyanideHCID 27334141,5-Bis(diphenylphosphino)pentaneHCID 591789101-(2-Chloro-6-methylpyrimidin-4-yl)-1'-(5-methylpyrazin-2-yl)-4,4'-bipiperidine

Product 1

HCID 545867804-Methyl-6-(4-(1-(5-methylpyrazin-2-yl)piperidin-4-yl)piperidin-1-yl)pyrimidine-2-carbonitrile

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
140 °C

Procedure

The 1-(2-chloro-6-methylpyrimidin-4-yl)-1′-(5-methylpyrazin-2-yl)-4,4′-bipiperidine (700 mg, 1.8 mmol) was placed in a pressure tube and anhydrous toluene (4 mL) added. To the stirred solution was added: palladium(II) acetate (41 mg, 0.18 mmol), 1,5-bis(dipenylphosphino)pentane (159 mg, 0.36 mmol), N,N,N′,N′-tetramethylethylenediamine (0.11 mL, 0.724 mmol), and potassium cyanide (235 mg, 3.62 mmol). The vessel was degassed with N2, sealed and heated at 140° C. for 16 hours. The mixture was allowed to cool to r.t., diluted with ethyl acetate (50 mL), washed with brine (10 mL×1), dried over magnesium sulfate, filtered and concentrated in vac. The residue was purified by chromatography on silica gel with 20% acetone: hexanes to yield the title compound.

Workup

  1. additionTo the stirred solution was added
  2. customThe vessel was degassed with N2
  3. customsealed
  4. temperatureto cool to r.t.
  5. additiondiluted with ethyl acetate (50 mL)
  6. washwashed with brine (10 mL×1)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vac
  10. customThe residue was purified by chromatography on silica gel with 20% acetone

Sources & evidence

ORD record
ord-c16d0230ac5542ef8e0b14d453917adb
Source dataset
uspto-grants-2013_05
Patent number
US08445499B2

Reaction notes

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