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 2195061노트

반응식

HRID 2195061 반응식
[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

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 2

HCID 962Water용매HCID 31374Dimethylacetamide용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-0827a4a2633244c4975e8dd1e90e2e49
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08334382B2

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