Dimethylformamide → 6-{4-[6-(4-Fluoro-phenyl)-2-(2-(S)-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-3-(R)-methyl-piperazin-1-yl}-5-chloro-nicotinonitrile

HRID 1444148노트

반응식

HRID 1444148 반응식
Br[C:2]1[CH:3]=[C:4]([Cl:34])[C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:19]=[C:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[N:17]=[C:16]([N:27]4[CH2:31][CH2:30][CH2:29][C@@H:28]4[CH3:32])[N:15]=3)[C@H:10]([CH3:33])[CH2:9]2)=[N:6][CH:7]=1.[CH3:35][N:36](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:26][C:23]1[CH:24]=[CH:25][C:20]([C:18]2[N:17]=[C:16]([N:27]3[CH2:31][CH2:30][CH2:29][C@@H:28]3[CH3:32])[N:15]=[C:14]([N:11]3[CH2:12][CH2:13][N:8]([C:5]4[C:4]([Cl:34])=[CH:3][C:2]([C:35]#[N:36])=[CH:7][N:6]=4)[CH2:9][C@H:10]3[CH3:33])[CH:19]=2)=[CH:21][CH:22]=1

참가 물질

5

반응물 2

HCID 6228DimethylformamideHCID 591683424-[4-(5-Bromo-3-chloro-pyridin-2-yl)-2-(R)-methyl-piperazin-1-yl]-6-(4-fluoro-phenyl)-2-(2-(S)-methyl-pyrrolidin-1-yl)-pyrimidine

생성물 1

HCID 591683766-{4-[6-(4-Fluoro-phenyl)-2-(2-(S)-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-3-(R)-methyl-piperazin-1-yl}-5-chloro-nicotinonitrile

시약·촉매·용매 2

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 178418397HCID 178418397, 화합물촉매

실험 절차

To a mixture of 4-[4-(5-bromo-3-chloro-pyridin-2-yl)-2-(R)-methyl-piperazin-1-y]-6-(4-fluoro-phenyl)-2-(2-(S)-methyl-pyrrolidin-1-yl)pyrimidine (700 mg) and Zn(CN)2 (94 mg) in DMF, add Pd(PPh3)4 (77 mg, 0.067 mmol). Purge the reaction mixture for 10 min with dry N2. Heat the stirring reaction mixture overnight at 80° C., cool to room temperature and partition between water and EtOAc. Dry the solution (Na2SO4), concentrate under reduced pressure. Purify the residue by flash column eluting with EtOAc-Hexanes (1:1) to afford the title compound as a white solid.

후처리

  1. customPurge the reaction mixture for 10 min with dry N2
  2. temperatureHeat
  3. customthe stirring reaction mixture overnight at 80° C.
  4. custompartition between water and EtOAc
  5. dry with materialDry the solution (Na2SO4)
  6. concentrationconcentrate under reduced pressure
  7. customPurify the residue by flash column
  8. washeluting with EtOAc-Hexanes (1:1)

출처 및 근거

ORD 기록
ord-fb0cc3f084544d179aa11b6ec4f01d43
출처 데이터셋
uspto-grants-2010_02
특허 번호
US07662830B2

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