4-(1-Pyrrolidinyl)piperidine → HCID 11577350, compound

HRID 1627555Notes

Reaction equation

HRID 1627555 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][C:11]([NH2:26])=[C:12]([O:14][CH:15]([C:17]3[C:22]([Cl:23])=[CH:21][CH:20]=[C:19]([F:24])[C:18]=3[Cl:25])[CH3:16])[CH:13]=2)=[CH:4][CH:3]=1.[N:27]1([CH:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[CH2:31][CH2:30][CH2:29][CH2:28]1>CN1CCCC1=O>[Cl:25][C:18]1[C:19]([F:24])=[CH:20][CH:21]=[C:22]([Cl:23])[C:17]=1[CH:15]([O:14][C:12]1[CH:13]=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([N:35]3[CH2:36][CH2:37][CH:32]([N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[CH2:33][CH2:34]3)=[N:7][CH:6]=2)[CH:9]=[N:10][C:11]=1[NH2:26])[CH3:16]

Participants

4

Reactant 2

HCID 787034-(1-Pyrrolidinyl)piperidineHCID 59599434HCID 59599434, compound

Product 1

HCID 11577350HCID 11577350, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

A tube was charged with 6′-bromo-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-[3,3′]bipyridinyl-6-ylamine (92 mg, 0.20 mmol), 4-pyrrolidin-1-yl-piperidine (0.62 g, 4.0 mmol) and N-methylpyrrolidinone (0.8 mL). The tube was sealed and the mixture was heated at 80° C. overnight. The temperature was increased to 100° C. for 5.5 hours and then heating was ceased. The reaction was partitioned between ethyl acetate and water. The phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over MgSO4 and concentrated by rotary evaporation. The residue was purified by silica gel chromatography using gradient elution of dichloromethane, methanol, ammonium hydroxide to afford 5″-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-4-pyrrolidin-1-yl-3,4,5,6-tetrahydro-2H-[1,2′;5′,3″]terpyridin-6″-ylamine (53 mg, 50%).

Workup

  1. customThe tube was sealed
  2. temperatureThe temperature was increased to 100° C. for 5.5 hours
  3. temperatureheating
  4. customThe reaction was partitioned between ethyl acetate and water
  5. customThe phases were separated
  6. extractionthe aqueous phase was extracted with ethyl acetate
  7. dry with materialThe combined organic phases were dried over MgSO4
  8. concentrationconcentrated by rotary evaporation
  9. customThe residue was purified by silica gel chromatography
  10. washelution of dichloromethane, methanol, ammonium hydroxide

Sources & evidence

ORD record
ord-91514a5aa4534d5d91d4929e219843a0
Source dataset
uspto-grants-2014_07
Patent number
US08785632B2

Reaction notes

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