Diisopropylethylamine → 4-[4-(5-bromo-3-methyl-pyridin-2-yl)-2-(R)-methyl-piperazin-1-yl]-6-(4-fluoro-phenyl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidine

HRID 2195061Notes

Reaction equation

HRID 2195061 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([N:14]3[CH2:19][CH2:18][NH:17][CH2:16][C@H:15]3[CH3:20])[N:11]=[C:10]([N:21]3[CH2:25][CH2:24][CH2:23][C@H:22]3[CH3:26])[N:9]=2)=[CH:4][CH:3]=1.Br[C:28]1[C:33]([CH3:34])=[CH:32][C:31]([Br:35])=[CH:30][N:29]=1.CCN(C(C)C)C(C)C>CC(N(C)C)=O.O>[Br:35][C:31]1[CH:32]=[C:33]([CH3:34])[C:28]([N:17]2[CH2:18][CH2:19][N:14]([C:12]3[CH:13]=[C:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[N:9]=[C:10]([N:21]4[CH2:25][CH2:24][CH2:23][C@H:22]4[CH3:26])[N:11]=3)[C@H:15]([CH3:20])[CH2:16]2)=[N:29][CH:30]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 8176802,5-Dibromo-3-methylpyridineHCID 591683354-(4-Fluoro-phenyl)-6-(2-(R)-methyl-piperazin-1-yl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidine

Product 1

HCID 591682874-[4-(5-bromo-3-methyl-pyridin-2-yl)-2-(R)-methyl-piperazin-1-yl]-6-(4-fluoro-phenyl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

Heat a mixture of 4-(4-fluoro-phenyl)-6-(2-(R)-methyl-piperazin-1-yl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidine (400 mg, 1.13 mmol), 2,5-dibromo-3-methyl-pyridine (367 mg, 1.46 mmol), and DIEA (218 mg, 1.69 mmol) in DMA at 135° C. for 96 h. Dilute with water, extract with EtOAc, and wash with brine. Dry the organic layer (Na2SO4) and concentrate under reduced pressure. Purify the residue by flash column chromatography eluting with EtOAc-Hexanes (1:10) to afford the title compound as a white solid.

Workup

  1. temperatureHeat
  2. extractionextract with EtOAc
  3. washwash with brine
  4. dry with materialDry the organic layer (Na2SO4)
  5. concentrationconcentrate under reduced pressure
  6. customPurify the residue by flash column chromatography
  7. washeluting with EtOAc-Hexanes (1:10)

Sources & evidence

ORD record
ord-0827a4a2633244c4975e8dd1e90e2e49
Source dataset
uspto-grants-2012_12
Patent number
US08334382B2

Reaction notes

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