Diisopropylethylamine → 6-{1-[(3S,4S)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethylamino}-nicotinonitrile

HRID 2191145Notes

Reaction equation

HRID 2191145 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C@H:11]([CH:14]([NH2:16])[CH3:15])[C@@H:10]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:25]1[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][N:26]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][C@H:11]([CH:14]([NH:16][C:25]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][N:26]=2)[CH3:15])[C@@H:10]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 50057186-Bromopyridine-3-carbonitrileHCID 594381231-[(3S,4S)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethylamine

Product 1

HCID 594381866-{1-[(3S,4S)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethylamino}-nicotinonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 610 mg (1.8 mmol) 1-[(3S,4S)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethylamine, 1.18 g (2.8 mmol) 2-bromo-5-cyano-pyridine and 0.838 g (2.8 mmol) DIPEA in 3.5 mL DMF was heated to 60° C. for 3 days. The mixture was evaporated, Na2CO3aq. was added and the mixture was extracted with ethyl acetate. The combined organic phases were dried with Na2SO4 and evaporated to dryness. The residue was purified by column chromatography on silica eluting with a gradient formed from DCM, methanol and NH3aq. to yield after evaporation of the product containing fractions 0.526 g (66%) of the title compound as off-white foam. MS (m/e): 431.4 [(M+H)+].

Workup

  1. customThe mixture was evaporated
  2. additionwas added
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialThe combined organic phases were dried with Na2SO4
  5. customevaporated to dryness
  6. customThe residue was purified by column chromatography on silica eluting with a gradient
  7. customformed from DCM, methanol and NH3aq
  8. customto yield
  9. customafter evaporation of the product
  10. additioncontaining fractions 0.526 g (66%) of the title compound as off-white foam

Sources & evidence

ORD record
ord-fd87ce8811a847ea83903bd58f58f6f6
Source dataset
uspto-grants-2012_12
Patent number
US08324248B2

Reaction notes

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