2-Methylpyrrolidine → 5-Chloro-6-{4-[6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-piperazin-1-yl}-nicotinic acid ethyl ester

HRID 1444103Notes

Reaction equation

HRID 1444103 reaction equation
[CH2:1]([O:3][C:4](=[O:32])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[C:22]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[N:21]=[C:20](Cl)[N:19]=3)[CH2:14][CH2:13]2)=[N:7][CH:6]=1)[CH3:2].[CH3:33][CH:34]1[CH2:38][CH2:37][CH2:36][NH:35]1>CC(N(C)C)=O>[CH2:1]([O:3][C:4](=[O:32])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([N:12]2[CH2:13][CH2:14][N:15]([C:18]3[CH:23]=[C:22]([C:24]4[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=4)[N:21]=[C:20]([N:35]4[CH2:36][CH2:37][CH2:38][CH:34]4[CH3:33])[N:19]=3)[CH2:16][CH2:17]2)=[N:7][CH:6]=1)[CH3:2]

Participants

4

Reactant 2

HCID 130032-MethylpyrrolidineHCID 591683325-Chloro-6-{4-[2-chloro-6-(4-fluoro-phenyl)-pyrimidin-4-yl]piperazin-1-yl}-nicotinic acid ethyl ester

Product 1

HCID 591682795-Chloro-6-{4-[6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-piperazin-1-yl}-nicotinic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Heat a mixture of 5-chloro-6-{4-[2-chloro-6-(4-fluoro-phenyl)-pyrimidin-4-yl]-piperazin-1-yl}-nicotinic acid ethyl ester (1.19 g, 0.0025 mol) and 2-methylpyrrolidine (2.5 mL, 0.025 mol) in DMA at 120° C. for 14 h. Partition the reaction mixture between EtOAc and water. Wash the organic layer with water (1×) and brine (1×), then dry (Na2SO4) and concentrate under reduced pressure. Filter the crude product through a silica gel pad (2 inches deep×3 inches in diameter) eluting with 700 mL of 30% EtOAc/bexanes. Concentrate under reduced pressure to give the title compound as an off-white foam.

Workup

  1. temperatureHeat
  2. customPartition the reaction mixture between EtOAc and water
  3. washWash the organic layer with water (1×) and brine (1×)
  4. dry with materialdry (Na2SO4)
  5. concentrationconcentrate under reduced pressure
  6. filtrationFilter the crude product through a silica gel pad (2 inches deep×3 inches in diameter)
  7. washeluting with 700 mL of 30% EtOAc/bexanes
  8. concentrationConcentrate under reduced pressure

Sources & evidence

ORD record
ord-9d36a0f4cce34fefaae50e2af9339909
Source dataset
uspto-grants-2010_02
Patent number
US07662830B2

Reaction notes

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