4-Methoxypiperidine → HCID 50906993, compound

HRID 1431365Notes

Reaction equation

HRID 1431365 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.[CH3:34][O:35][CH:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]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[C:5]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[N:6][CH:7]=[C:2]([N:39]3[CH2:40][CH2:41][CH:36]([O:35][CH3:34])[CH2:37][CH2:38]3)[CH:3]=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 776664-MethoxypiperidineHCID 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 50906993HCID 50906993, 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 (0.057 g, 0.110 mmol), 4-methoxypiperidine (commercially available from Oakwood Products, Inc.) (0.035 g, 0.30 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.013 g, 0.014 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl (0.012 g, 0.026 mmol), and sodium tert-butoxide (0.056 g, 0.58 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 (0-35% EtOAc in hexanes) to afford a light yellow solid as 5,7-difluoro-N-(5-(4-methoxy-1-piperidinyl)-2-(4-morpholinyl)-3-pyridinyl)-3-methyl-2-(2-pyridinyl)-4-quinolinamine. Mass Spectrum ESI (pos.) m/e: 547.2 (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 (0-35% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0ffa7aeca7f4490ebc6875d5072b70ae
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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