Potassium Carbonate → 4-[4-(3-Chloro-6-methoxy-pyridin-2-yl)-2-methyl-piperazin-1-yl]-6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidine

HRID 230958Notes

Reaction equation

HRID 230958 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[N:5]=[C:4]([N:15]2[CH2:19][CH2:18][CH2:17][CH:16]2[CH3:20])[N:3]=1.[Cl:21][C:22]1[C:23]([N:30]2[CH2:35][CH2:34][NH:33][C@H:32]([CH3:36])[CH2:31]2)=[N:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=1.C([O-])([O-])=O.[K+].[K+]>CC(N(C)C)=O>[Cl:21][C:22]1[C:23]([N:30]2[CH2:35][CH2:34][N:33]([C:2]3[CH:7]=[C:6]([C:8]4[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=4)[N:5]=[C:4]([N:15]4[CH2:19][CH2:18][CH2:17][CH:16]4[CH3:20])[N:3]=3)[CH:32]([CH3:36])[CH2:31]2)=[N:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 121612594-Chloro-6-(4-fluorophenyl)-2-(2-methylpyrrolidin-1-yl)pyrimidineHCID 577611611-(3-chloro-6-methoxy-pyridin-2-yl)-3-(R)-methyl-piperazine

Product 1

HCID 688239464-[4-(3-Chloro-6-methoxy-pyridin-2-yl)-2-methyl-piperazin-1-yl]-6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidine

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Heat a mixture of 4-chloro-6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidine (440 mg, 1.51 mmol), 1-(3-chloro-6-methoxy-pyridin-2-yl)-3-(R)-methyl-piperazine (400 mg, 1.66 mmol), and K2CO3 (230 mg, 1.66 mmol) in DMA at 120° C. for 16 hours. Partition the mixture between EtOAc and water, dry (Na2SO4) the organic layer and concentrate under reduced pressure. Purify with flash silica gel column eluting with 10% EtOAc/hexanes. Concentrate under reduced pressure to give the title compound. 1H NMR (300 MHz, CDCl3): δ1.36 (m, 6H, 2×CH3); 1.70 (m, 1H, CH2CH2); 1.93 (m, 1H, CH2CH2); 2.06 (m, 2H, CH2CH2); 3.05 (m, 2H); 3.38 (m, 1H); 3.70 (m, 2H); 3.88 (s, 3H, OCH3); 3.90 (m, 2H); 4.35 (m, 2H); 4.70 (m, 1H); 6.232 (s, 1H); 6.30 (d, 1H, J=8.4 Hz); 7.12 (m, 2H); 7.46 (d, J=9.0 Hz, 1H); 8.00 (m, 2H).

Workup

  1. temperatureHeat
  2. customPartition the mixture between EtOAc and water
  3. dry with materialdry (Na2SO4) the organic layer
  4. concentrationconcentrate under reduced pressure
  5. customPurify with flash silica gel column
  6. washeluting with 10% EtOAc/hexanes
  7. concentrationConcentrate under reduced pressure

Sources & evidence

ORD record
ord-5601918dbecd4201aeb25007991dd4e9
Source dataset
uspto-grants-2009_07
Patent number
US07566712B2

Reaction notes

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