Binap, (A+-)- → 5-[(3R)-3-methylpiperazin-1-yl]pyridine-2-carbonitrile

HRID 1868121Notes

Reaction equation

HRID 1868121 reaction equation
[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][NH:3]1.Br[C:9]1[CH:10]=[CH:11][C:12]([C:15]#[N:16])=[N:13][CH:14]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>ClCCl.C1(C)C=CC=CC=1>[CH3:1][C@H:2]1[NH:3][CH2:4][CH2:5][N:6]([C:9]2[CH:10]=[CH:11][C:12]([C:15]#[N:16])=[N:13][CH:14]=2)[CH2:7]1

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 8171545-Bromopyridine-2-carbonitrileHCID 73304342-Methylpiperazine, (R)-HCID 23676156Sodium t-butoxide

Product 1

HCID 442495865-[(3R)-3-methylpiperazin-1-yl]pyridine-2-carbonitrile

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of (R)-2-methyl-piperazine (1.0 g, 9.98 mmol), 5-bromo 2-cyanopyridine (1.66 g, 9.08 mmol), tris(dibenzylidineacetone)dipalladium (0) (83.15 mg, 0.0908 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphtyl (169.37 mg, 0.272 mmol) and sodium tert-butoxide (1.09 g, 11.35 mmol) were charged to a microwave vial. Toluene (10.0 mL) was introduced under nitrogen atmosphere and the reaction mixture was irradiated at 110° C. for 35 minutes. Reaction was complete as determined by TLC. Reaction mixtures was diluted with dichloromethane, washed with water, saturated brine then dried over Na2SO4 and concentrated. The crude product was purified via flash column chromatography to yield 5-[(3R)-3-methylpiperazin-1-yl]pyridine-2-carbonitrile as brown color oil (1.15 g, 39.1% yield).

Workup

  1. additionwere charged to a microwave vial
  2. customthe reaction mixture was irradiated at 110° C. for 35 minutes
  3. customReaction
  4. customReaction mixtures
  5. washwashed with water, saturated brine
  6. dry with materialthen dried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude product was purified via flash column chromatography

Sources & evidence

ORD record
ord-e0f89058f3204bf586a657ab74b39a6f
Source dataset
uspto-grants-2009_12
Patent number
US07632838B2

Reaction notes

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