4-Cyanopiperidine → HCID 58547825, compound

HRID 2207814Notes

Reaction equation

HRID 2207814 reaction equation
Br[C:2]1[C:3]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:24]=[CH:23][C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[N:16]=3)[CH2:11][CH2:10]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[NH:25]1[CH2:30][CH2:29][CH:28]([C:31]#[N:32])[CH2:27][CH2:26]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+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:23]=[CH:24][C:15]=1[N:12]1[CH2:13][CH2:14][CH:9]([O:8][C:3]2[C:2]([N:25]3[CH2:30][CH2:29][CH:28]([C:31]#[N:32])[CH2:27][CH2:26]3)=[CH:7][CH:6]=[CH:5][N:4]=2)[CH2:10][CH2:11]1

Participants

7

Reactant 4

HCID 1382234-CyanopiperidineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 58547880HCID 58547880, compound

Product 1

HCID 58547825HCID 58547825, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 2-(4-((3-bromopyridin-2-yl)oxy)piperidin-1-yl)quinoline (see PREPARATION P2.2; 383 mg, 1.0 mmol) in toluene (10 mL) were added piperidine-4-carbonitrile (110 mg, 1.0 mmol), Pd2(dba)3 (92 mg, 0.1 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) (62 mg, 0.1 mmol) and sodium tert-butoxide (t-BuONa) (180 mg, 2.0 mmol). The mixture was stirred and heated at reflux overnight under N2 atmosphere. Then the reaction mixture was filtered, diluted with water (50 mL), and extracted with EtOAc (3×20 mL). The combined organic extracts were washed with water (60 mL) and brine (60 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (20% to 50% EtOAc in hexanes) to give the title product (290 mg, 0.7 mmol, 70% yield) as white solid. ESI-MS (M+1): 414 calc. for C25H27BrN5O 413.

Workup

  1. temperatureheated
  2. temperatureat reflux overnight under N2 atmosphere
  3. filtrationThen the reaction mixture was filtered
  4. additiondiluted with water (50 mL)
  5. extractionextracted with EtOAc (3×20 mL)
  6. washThe combined organic extracts were washed with water (60 mL) and brine (60 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customThe filtrate was evaporated in vacuo
  10. customthe residue was purified by flash column chromatography on silica gel (20% to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-315e9448521f41d094994b5c7cfbc407
Source dataset
uspto-grants-2016_06
Patent number
US09376450B2

Reaction notes

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