4-Cyanopiperidine → HCID 50907187, compound

HRID 1431364Notes

Reaction equation

HRID 1431364 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:14][C:15]2[C:24]3[C:19](=[CH:20][C:21]([F:26])=[CH:22][C:23]=3[F:25])[N:18]=[C:17]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=3)[C:16]=2[CH3:33])[C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.[NH:34]1[CH2:39][CH2:38][CH:37]([C:40]#[N:41])[CH2:36][CH2:35]1.C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.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].O>[F:25][C:23]1[CH:22]=[C:21]([F:26])[CH:20]=[C:19]2[C:24]=1[C:15]([NH:14][C:4]1[CH:3]=[C:2]([N:34]3[CH2:39][CH2:38][CH:37]([C:40]#[N:41])[CH2:36][CH2:35]3)[CH:7]=[N:6][C:5]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)=[C:16]([CH3:33])[C:17]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1)=[N:18]2

Participants

8

Reactant 4

HCID 1382234-CyanopiperidineHCID 23676156Sodium t-butoxideHCID 59631101N-(5-bromo-2-morpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amineHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 50907187HCID 50907187, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A stirred mixture of N-(5-bromo-2-morpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine (0.049 g, 0.096 mmol), piperidine-4-carbonitrile (commercially available from Oakwood Products, Inc.) (0.023 g, 0.21 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl (0.0097 g, 0.020 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.0095 g, 10.4 μmol), and sodium tert-butoxide (0.044 g, 0.46 mmol) in dry toluene (3.0 mL) was purged three times with argon and placed under vacuum three times, then the mixture was heated to 100° C. After 21.5 h, the reaction was cooled to rt, then treated with water. After extracting twice with DCM:MeOH (95:5), the organics were combined and dried over anhydrous magnesium sulfate. After filtration and concentration the residue was purified on basic alumina (10-50% EtOAc in hexanes) to afford a light yellow solid as 1-(5-((5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)amino)-6-(4-morpholinyl)-3-pyridinyl)-4-piperidinecarbonitrile. Mass Spectrum ESI (pos.) m/e: 542.2 (M+H)+.

Workup

  1. temperaturethe reaction was cooled to rt
  2. extractionAfter extracting twice with DCM:MeOH (95:5)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationAfter filtration and concentration the residue
  5. customwas purified on basic alumina (10-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-4b8f7cc688134f7fb0f466a6618cf1cb
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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